Background and Objectives: The trends in metabolic dysfunction-associated steatotic liver disease (MASLD) and related metabolic dysfunctions in Japan are unknown. Thus, we aimed to clarify these trends before the novel coronavirus disease 2019 pandemic in Japan. Materials and Methods: We included Japanese individuals aged 25-79 years who underwent health examinations at our center. We analyzed anthropometry, lifestyle-related disease, and nutritional intake in relation to MASLD trends from 2010-2019. Results: The prevalence of MASLD increased in all ages and body mass index (BMI) classes, reaching 30.3% in males and 16.1% in females, with MASLD accounting for 75% of steatotic liver cases and more than half of all type 2 diabetes mellitus (T2DM) and high waist circumference (HWC) cases. The increase in the prevalence of MASLD was thought to be largely attributable to an increase in that of the incidence of steatotic liver itself, and there was no increase in the prevalence of other factors, such as overweight, T2DM, hypertension, and dyslipidemia. The prevalence of glucose metabolic disorders (GMDs) and hypertension decreased. National nutritional data showed an increase in energy intake, total fat, saturated fatty acids, monounsaturated fatty acids, and polyunsaturated fatty acids, which correlated with a decrease in GMDs. Salt intake also decreased, which correlated with hypertension. The MASLD group had a higher prevalence of all related metabolic factors than the non-MASLD group, especially HWC, T2DM, and hyperlipidemia. Conclusions: The prevalence of MASLD increased with that of steatotic liver, regardless of age or BMI. A relationship between increased dietary fat, increased steatotic liver, and decreased GMDs was suggested.

Increased production of advanced glycation end products (AGEs) among reducing sugars (glucose, fructose, galactose, or ribose) and amino acids/proteins via non-enzymatic Maillard reaction can be found in lifestyle-related disease (LSRD), metabolic syndrome (MetS), and obesity and immune-related diseases. Increased serum levels of AGEs may induce aging, diabetic complications, cardiovascular diseases (CVD), neurodegenerative diseases (NDD), cancer, and inflamm-aging (inflammation with immunosenescence). The Maillard reaction can also occur among reducing sugars and lipoproteins or DNAs to alter their structure and induce immunogenicity/genotoxicity for carcinogenesis. AGEs, as danger-associated molecular pattern molecules (DAMPs), operate via binding to receptor for AGE (RAGE) or other scavenger receptors on cell surface to activate PI3K-Akt-, P38-MAPK-, ERK1/2-JNK-, and MyD88-induced NF-κB signaling pathways to mediate various pathological effects. Recently, the concept of \"inflamm-aging\" became more defined, and we have unveiled some interesting findings in relation to it. The purpose of the present review is to dissect the potential molecular basis of inflamm-aging in patients with diabetes and immune-mediated diseases caused by different AGEs.

BACKGROUND: Because patients often already have coronary artery disease (CAD) at the time of a coronary artery computed tomography angiography (CCTA) examination, we examined the medications prescribed by medical doctors for lifestyle-related diseases and investigated what possible role pharmacists can play in prescribing.
METHODS: Patients (n = 1357) who underwent CCTA examination were divided into two groups according to the presence or absence of lifestyle-related diseases [hypertension (HTN), dyslipidemia (DL) and diabetes mellitus (DM)], and the relationship between the presence or absence of CAD was examined.
RESULTS: The rate of CAD was significantly higher in patients with HTN, DL or DM than in patients without these diseases. The blood pressure in the HTN group was 140 ± 20/79 ± 13 mmHg, the low-density lipoprotein cholesterol value in the DL group was 119 ± 35 mg/dL, and the hemoglobin A1c value in the DM group was 7.0 ± 1.1%, all of which were poorly controlled. Anti-hypertensive drugs were used at low rates in the HTN group, statins were used in 47% and ezetimibe was used in 4% of the DL group, and dipeptidyl peptidase-4 inhibitors were used in 41% of the DM group.
CONCLUSIONS: Since the rate of CAD (+) was high and control of the three major lifestyle-related diseases was poor, pharmacists should advise medical doctors to use combinations of drugs.

Objectives: This study examined the actual conditions of service provision to foreign residents (FRs) addressing prevention of lifestyle-related diseases (LRDs) and disaster preparedness/disaster responses (DPRs) in Japanese municipalities. Materials and Methods: A cross-sectional study was performed using a self-administered questionnaire with representatives of public health nurses in each municipality in Japan from December 2021 to January 2022. Results: Services considering FRs are more likely to be implemented in cities than in towns, and in municipalities where FRs account for ≥2.2% of the population (proportion of FRs in the Japanese population at the time of the study) than in those with fewer FRs. Cities have larger populations and greater financial resources than towns. Factors associated with the implementation of services and measures necessary for providing services to FRs were the classification of the municipality as a city, a high percentage of FRs, and large variation in corresponding nationalities/countries of origin. Conclusions: Cross-disciplinary efforts and collaborations need to be strengthened to share available resources within local governments and experiences in providing services for FRs in other divisions/sections, rather than considering only how to provide services for FRs in the public health division/section.

Autophagy mediates the degradation of intracellular macromolecules and organelles within lysosomes. There are three types of autophagy: macroautophagy, microautophagy, and chaperone-mediated autophagy. Heat shock protein 70.1 (Hsp70.1) exhibits dual functions as a chaperone protein and a lysosomal membrane stabilizer. Since chaperone-mediated autophagy participates in the recycling of ∼30% cytosolic proteins, its disorder causes cell susceptibility to stress conditions. Cargo proteins destined for degradation such as amyloid precursor protein and tau protein are trafficked by Hsp70.1 from the cytosol into lysosomes. Hsp70.1 is composed of an N-terminal nucleotide-binding domain (NBD) and a C-terminal domain that binds to cargo proteins, termed the substrate-binding domain (SBD). The NBD and SBD are connected by the interdomain linker LL1, which modulates the allosteric structure of Hsp70.1 in response to ADP/ATP binding. After the passage of the Hsp70.1-cargo complex through the lysosomal limiting membrane, high-affinity binding of the positive-charged SBD with negative-charged bis(monoacylglycero)phosphate (BMP) at the internal vesicular membranes activates acid sphingomyelinase to generate ceramide for stabilizing lysosomal membranes. As the integrity of the lysosomal limiting membrane is critical to ensure cargo protein degradation within the acidic lumen, the disintegration of the lysosomal limiting membrane is lethal to cells. After the intake of high-fat diets, however, β-oxidation of fatty acids in the mitochondria generates reactive oxygen species, which enhance the oxidation of membrane linoleic acids to produce 4-hydroxy-2-nonenal (4-HNE). In addition, 4-HNE is produced during the heating of linoleic acid-rich vegetable oils and incorporated into the body via deep-fried foods. This endogenous and exogenous 4-HNE synergically causes an increase in its serum and organ levels to induce carbonylation of Hsp70.1 at Arg469, which facilitates its conformational change and access of activated μ-calpain to LL1. Therefore, the cleavage of Hsp70.1 occurs prior to its influx into the lysosomal lumen, which leads to lysosomal membrane permeabilization/rupture. The resultant leakage of cathepsins is responsible for lysosomal cell death, which would be one of the causative factors of lifestyle-related diseases.

The number of patients with lifestyle-related diseases such as type 2 diabetes mellitus (T2DM) and metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as non-alcoholic fatty liver disease (NAFLD), has continued to increase worldwide. Therefore, development of innovative therapeutic methods targeting lifestyle-related diseases is required. Gene therapy has attracted considerable attention as an advanced medical treatment. Safe and high-performance vectors are essential for the practical application of gene therapy. Replication-incompetent adenovirus (Ad) vectors are widely used in clinical gene therapy and basic research. Here, we developed a novel Ad vector, named Ad-E4-122aT, exhibiting higher and longer-term transgene expression and lower hepatotoxicity than conventional Ad vectors. We also elucidated the mechanisms underlying Ad vector-induced hepatotoxicity during the early phase using Ad-E4-122aT. Next, we examined the therapeutic effects of the genes of interest, namely zinc finger AN1-type domain 3 (ZFAND3), lipoprotein lipase (LPL), and lysophospholipid acyltransferase 10 (LPLAT10), on lifestyle-related diseases using Ad-E4-122aT. We showed that the overexpression of ZFAND3 in the liver improved glucose tolerance and insulin resistance. Liver-specific LPL overexpression suppressed hepatic lipid accumulation and improved glucose metabolism. LPLAT10 overexpression in the liver suppressed postprandial hyperglycemia by increasing glucose-stimulated insulin secretion. Furthermore, we also focused on foods to advance research on the pathophysiology and treatment of lifestyle-related diseases. Cranberry and calamondin, which are promising functional foods, attenuated the progression of MASLD/NAFLD. Our findings will aid the development of new therapeutic methods, including gene therapy, for lifestyle-related diseases such as T2DM and MASLD/NAFLD.

Objective To examine the trends and relationships between nonalcoholic fatty liver disease (NAFLD) and hypertension, type 2 diabetes mellitus (T2DM), and dyslipidemia from fiscal year (FY) 2008, when specific health checkups (SHCs) were initiated in Japan, to FY 2019 and the relationship between NAFLD trends and dietary nutrition. Methods A total of 48,332 participants (25,121 men and 23,211 women) diagnosed with NAFLD who underwent health checkups, including ultrasonography, from FY 2008 to FY 2019 were included. A fatty liver was diagnosed using ultrasonography. The dietary nutrient intake status was based on data from the National Health and Nutrition Survey, Japan. Results Over 12 years, NAFLD prevalence increased from 26.9% to 43.1% in men (p<0.0001) and from 9.9% to 17.9% in women (p<0.0001) in all body mass index (BMI) groups except for obese II (according to the World Health Organization Asia-Pacific criteria) in men and underweight in women and almost all age groups. T2DM prevalence increased in men (from 9.0% to 10.7%, p=0.0234), and obesity and higher waist circumference rates increased in women (from 16.0% to 18.0%, p=0.0059 and from 8.1% to 10%, respectively, p=0.0006). The dietary nutrient intake increased with regard to the total fat, fat/energy ratio, saturated fatty acids, monounsaturated fatty acids, and n6/n3 fatty acid ratio in both men and women, and these nutrient trends were correlated with NAFLD prevalence (all p≤0.0005). Conclusion In Japan, NAFLD increased in both men and women regardless of the BMI and age, even after starting SHCs. An unbalanced fat intake may be one of the major reasons for this increase.

BACKGROUND: Osteoporosis is a multifactorial disorder in which nutrition is associated with its onset and progression. Excessive salt intake is closely associated with the onset and progression of various diseases, such as osteoporosis and hypertension. We investigated the effects of dietary salt intake on bone density in the general female population.
METHODS: In 884 female participants (60.1 ± 10.1 years old) who visited our hospital for an annual physical checkup, salt intake (g/day) was assessed using a spot urine sample, and bone density was evaluated as a speed of sound (m/s) of ultrasonic pulses in a calcaneus by quantitative ultrasound. We investigated the relationship between bone density and salt intake and the differences in bone density or salt intake between the presence and absence of lifestyle-related diseases such as hypertension, diabetes mellitus and dyslipidaemia.
RESULTS: The average bone density and salt intake were 1497 ± 26 m/s and 8.5 ± 1.8 g/day, respectively. Univariate and multivariate regression analyses revealed that bone density was significantly negatively associated with salt intake. Bone density was lower, and salt intake was higher in participants with hypertension, diabetes mellitus and dyslipidaemia than in those without. After adjusting for age, hypertension, diabetes mellitus and dyslipidaemia, bone density was negatively correlated with salt intake.
CONCLUSIONS: We confirmed that excessive salt intake reduces bone density independently of age and lifestyle-related diseases in the general female population. Since dietary salt intake is a modifiable factor, osteoporosis can be prevented by dietary intervention, including salt reduction.

Because decedents undergoing forensic autopsies would have behaved normally before death, prostate volume according to age group can be confirmed with forensic autopsy materials. The objectives of this study were to first confirm the current prostate volume by age and then determine diseases that can influence prostate volume using forensic autopsy materials. Prostate specimens were collected from forensic autopsies performed at Shiga University of Medical Science, Japan, between January 2015 and December 2019. Overall, 207 decedents were included in the study. Prostate volume was measured by the Archimedes\' principle. Concomitant diseases were determined by the past medical histories and autopsy results. The mean crude prostate volume was 29.1 ± 10.3 mL (range, 2.8-88.0 mL). The crude prostate volume increased with age. The mean corrected prostate volume (divided by body surface area) was significantly higher in patients with atherosclerosis than in those without. However, multiple regression analysis revealed that only age influenced the corrected prostate volume. Age was the only significant influencing factor for prostate volume. We propose applying age estimation using prostate volume for forensic medicine purposes. Because prostate volume was not influenced by concomitant disease, it would be valuable to estimate the decedent\'s age using the prostate volume.

Lifestyle-related diseases are among the leading causes of death and disability. Their rapid increase worldwide has called for low-cost, scalable solutions to promote health behavior changes. Digital health coaching has proved to be effective in delivering affordable, scalable programs to support lifestyle change. This approach increasingly relies on asynchronous text-based interventions to motivate and support behavior change. Although we know that empathy is a core element for a successful coach-user relationship and positive patient outcomes, we lack research on how this is realized in text-based interactions. Systemic functional linguistics (SFL) is a linguistic theory that may support the identification of empathy opportunities (EOs) in text-based interactions, as well as the reasoning behind patients\' linguistic choices in their formulation.
This study aims to determine whether empathy and SFL approaches correspond and complement each other satisfactorily to study text-based communication in a health coaching context. We sought to explore whether combining empathic assessment with SFL categories can provide a means to understand client-coach interactions in asynchronous text-based coaching interactions.
We retrieved 148 text messages sent by 29 women who participated in a randomized trial of telecoaching for the prevention of gestational diabetes mellitus (GDM) and postnatal weight loss. We conducted a pilot study to identify users\' explicit and implicit EOs and further investigated these statements using the SFL approach, focusing on the analysis of transitivity and thematic analysis.
We identified 164 EOs present in 42.37% (3478/8209) of the word count in the corpus. These were mainly negative (n=90, 54.88%) and implicit (n=55, 60.00%). We distinguished opening, content and closing messages structures. Most of the wording was found in the content (n=7077, 86.21%) with a declarative structure (n=7084, 86.30%). Processes represented 22.4% (n=1839) of the corpus, with half being material (n=876, 10.67%) and mostly related to food and diet (n=196, 54.92%), physical activity (n=96, 26.89%), and lifestyle goals (n=40, 11.20%).
Our findings show that empathy and SFL approaches are compatible. The results from our transitivity analysis reveal novel insights into the meanings of the users\' EOs, such as their seek for help or praise, often missed by health care professionals (HCPs), and on the coach-user relationship. The absence of explicit EOs and direct questions could be attributed to low trust on or information about the coach\'s abilities. In the future, we will conduct further research to explore additional linguistic features and code coach messages.
Australian New Zealand Clinical Trials Registry (ANZCTR) ACTRN12620001240932; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=380020.