The microRNA miR-22 inhibits the histone deacetylase HDAC4 to promote T(H)17 cell-dependent emphysema.

Smoking-related emphysema is a chronic inflammatory disease driven by the T(H)17 subset of helper T cells through molecular mechanisms that remain obscure. Here we explored the role of the microRNA miR-22 in emphysema. We found that miR-22 was upregulated in lung myeloid dendritic cells (mDCs) of smokers with emphysema and antigen-presenting cells (APCs) of mice exposed to smoke or nanoparticulate carbon black (nCB) through a mechanism that involved the transcription factor NF-κB. Mice deficient in miR-22, but not wild-type mice, showed attenuated T(H)17 responses and failed to develop emphysema after exposure to smoke or nCB. We further found that miR-22 controlled the activation of APCs and T(H)17 responses through the activation of AP-1 transcription factor complexes and the histone deacetylase HDAC4. Thus, miR-22 is a critical regulator of both emphysema and T(H)17 responses.

Pan-Cancer Proteomics Analysis Reveals Wiskott-Aldrich Syndrome Protein as a Potential Regulator of Programmed Death-Ligand 1.

The programmed death-ligand 1 (PD-L1) is a key mediator of immunosuppression in the tumor microenvironment. The expression of PD-L1 in cancer cells is useful for the clinical determination of an immune checkpoint blockade (ICB). However, the regulatory mechanism of the PD-L1 abundance remains incompletely understood. Here, we integrated the proteomics of 52 patients with solid tumors and examined immune cell infiltration to reveal PD-L1-related regulatory modules. Wiskott-Aldrich syndrome protein (WASP) was identified as a potential regulator of PD-L1 transcription. In two independent cohorts containing 164 cancer patients, WASP expression was significantly associated with PD-L1. High WASP expression contributed to immunosuppressive cell composition, including cells positive for immune checkpoints (PD1, CTLA4, TIGIT, and TIM3), FoxP3+ Treg cells, and CD163+ tumor-associated macrophages. Overexpression of WASP increased, whereas knockdown of WASP decreased the protein level of PD-L1 in cancer cells without alteration of PD-L1 protein stability. The WASP-mediated cell migration and invasion were markedly attenuated by the silence of PD-L1. Collectively, our data suggest that WASP is a potential regulator of PD-L1 and the WASP/PD-L1 axis is responsible for cell migration and an immunosuppressive microenvironment.

Immune cell patterns before and after neoadjuvant immune checkpoint blockade combined with chemoradiotherapy in locally advanced esophageal squamous cell carcinoma.

BACKGROUND: Neoadjuvant immune checkpoint blockade (ICB) combined with chemoradiotherapy offers high pathologic complete response (pCR) rate for patients with locally advanced esophageal squamous cell carcinomas (ESCC). But the dynamic tumor immune microenvironment modulated by such neoadjuvant therapy remains unclear. PATIENTS AND METHODS: A total of 41 patients with locally advanced ESCC were recruited. All patients received neoadjuvant toripalimab combined with concurrent chemoradiotherapy. Matched pre- and post-treatment tissues were obtained for fluorescent multiplex immunohistochemistry (mIHC) and IHC analyses. The densities and spatial distributions of immune cells were determined by HALO modules. The differences of immune cell patterns before and after neoadjuvant treatment were investigated. RESULTS: In the pre-treatment tissues, more stromal CD3 + FoxP3 + Tregs and CD86+/CD163 + macrophages were observed in patients with residual tumor existed in the resected lymph nodes (pN1), compared with patients with pCR. The majority of macrophages were distributed in close proximity to tumor nest in pN1 patients. In the post-treatment tissues, pCR patients had less CD86 + cell infiltration, whereas higher CD86 + cell density was significantly associated with higher tumor regression grades (TRG) in non-pCR patients. When comparing the paired pre- and post-treatment samples, heterogeneous therapy-associated immune cell patterns were found. Upon to the treatment, CD3 + T lymphocytes were slightly increased in pCR patients, but markedly decreased in non-pCR patients. In contrast, a noticeable increase and a less obvious decrease of CD86 + cell infiltration were respectively depicted in non-pCR and pCR patients. Furthermore, opposite trends of the treatment-induced alterations of CD8 + and CD15 + cell infiltrations were observed between pN0 and pN1 patients. CONCLUSIONS: Collectively, our data demonstrate a comprehensive picture of tumor immune landscape before and after neoadjuvant ICB combined with chemoradiotherapy in ESCC. The infiltration of CD86 + macrophage may serve as an unfavorable indicator for neoadjuvant toripalimab combined with chemoradiotherapy.

Suffering and adjustment: a grounded theory of the process of coping with financial toxicity among young women with breast cancer.

PURPOSE: To explore the process of coping with financial toxicity among young women with breast cancer and formulate a grounded theory that serves as a foundation for creating intervention strategies aimed at supporting cancer survivors. METHODS: A qualitative study using the Corbin and Strauss variant of grounded theory. A series of in-depth interviews were carried out with young women with breast cancer (n = 29) using the theoretical sampling method. We analyzed data by coding core categories in the patients' coping processes and developing theory around these categories. Data collection and analysis were performed simultaneously. RESULTS: A substantial theory of the process of coping with financial toxicity among young female breast cancer survivors was constructed. Two core concepts, suffering and adjustment, were identified. Young women with breast cancer suffered from financial toxicity, which was related to risk factors, coping resources, and unmet needs. To overcome financial toxicity, young women with breast cancer adjusted by reshaping consumption concept, re-dividing of family functions, re-planning of occupation career, and rebuilding life confidence. CONCLUSION: This qualitative study constructed a theory delineating the coping strategies employed by young women with breast cancer in response to financial toxicity, offering profound insights into the intricacies of cancer-related financial toxicity. Identifying risk factors, enhancing coping resources, and meeting unmet needs would be helpful to patients' adjustment to financial stress.

Time Trends in Income-related Differences in Food Group Intakes: The National Health and Nutrition Survey, Japan in 2010, 2014, and 2018.

BACKGROUND: We aimed to clarify whether differences in food group intake according to household income have changed over the last decade in Japanese people aged 20 years or older. METHODS: This cross-sectional study was based on the 2010, 2014, and 2018 National Health and Nutrition Surveys in Japan. Food intake was assessed using a 1-day semi-weighed household dietary record. The participants were categorized into three groups based on their income. The mean of each food intake according to the income group was estimated by adjusting for age, occupation, and number of participants from the same household. The significance of the interaction terms between income and survey year was evaluated to assess the change in income-related differences in food intake over time. RESULTS: Cereal intake was lower in the middle- and the highest-income groups than in the lowest-income group, regardless of sex, and the interaction between income and year was nonsignificant for cereal intake. In the former two surveys, vegetable intake was higher among the highest-income women, while in the 2018 survey, the vegetable intake decreased in the women in the middle- and the highest-income groups. The interaction between income and year was significant for vegetable intake among the women. For other foods, the differences in intake among the income groups did not significantly change over time. CONCLUSION: The tendency for lower cereal intake in the higher-income groups was consistent over time in both the sexes, and the tendency for higher vegetable intake in the highest income women disappeared over time.

[Corrigendum: How accurate are self-reported anthropometrics among the Japanese? A scoping review].

　Nihon Koshu Eisei Zasshi(JAPANESE JOURNAL OF PUBLIC HEALTH), Vol. 70 (2023) No. 12 pp.817-827.

Therapeutic targeting of hypoxia inducible factor in acute respiratory distress syndrome.

Acute respiratory distress syndrome (ARDS) is characterized by bilateral chest infiltration and acute hypoxic respiratory failure. ARDS carries significant morbidity and mortality despite advancements in medical management, calling for the development of novel therapeutic targets. Hypoxia-inducible factor (HIF) is a heterodimeric protein involved in various essential pathways, including metabolic reprogramming, immune modulation, angiogenesis and cell cycle regulation. HIF is routinely degraded in homeostasis conditions via the prolyl hydroxylase domain/von Hippel-Lindau protein pathway. However, HIF is stabilized in ARDS via various mechanisms (oxygen-dependent and independent) as an endogenous protective pathway and plays multifaceted roles in different cell populations. This review focuses on the functional role of HIF and its target genes during ARDS, as well as how HIF has evolved as a therapeutic target in current medical management.

Analysis of urethral blood flow by high-resolution laser speckle contrast imaging in a rat model of vaginal distension.

OBJECTIVE: To investigate the feasibility of laser speckle contrast imaging (LSCI) for monitoring urethral blood flow (UBF). MATERIALS AND METHODS: In this study, 18 healthy, virgin female Sprague-Dawley rats aged 8-week-old were used. The animals were divided into the sham group (n = 9) and the vaginal distension (VD) group (n = 9). The sham group underwent one catheterization of the vagina without distension and the VD group underwent one VD. Following the VD or sham treatment for one week, LSCI assessment of urethral blood flow was performed during bladder filling and leak point pressure (LPP) process. RESULTS: During the LPP process, in the VD group, the mean LPP was significantly lower than in the sham group (p < 0.05) and the mean UBF level was also significantly lower than in the sham group (p < 0.05) in the LPP condition. The mean relative change of UBF (Δ Flow) was significantly different between the sham group and VD group. The value was 0.646 ± 0.229 and 0.295 ± 0.19, respectively (p < 0.05). During the bladder filling process, the VD group had a significant lower mean UBF level than the sham group under full bladder conditions (p = 0.008). The mean ΔFlow was also significantly lower than in the sham group. The value was 0.115 ± 0.121 and 0.375 ± 0.127, respectively (p = 0.016). CONCLUSIONS: The results confirmed that LSCI was able to determine UBF in female rats. The VD group had lower baseline UBF and lower increases in UBF during bladder filling and LPP process compared with the sham group.

The association of highly processed food consumption with food choice values and food literacy in Japanese adults: a nationwide cross-sectional study.

BACKGROUND: Highly processed food (HPF) consumption is increasing globally and has become a prominent public health concern. However, the relationship between HPF consumption and food choice values and food literacy is unknown. This study aimed to examine the association of HPF consumption with food choice values and food literacy. METHODS: This cross-sectional study used data from a nationwide questionnaire survey conducted in 2018 among 2232 Japanese adults aged 18-80 years. We assessed eight food choice values (accessibility, convenience, health/weight control, tradition, sensory appeal, organic, comfort, and safety) using a 25-item scale, and food literacy characterised by nutrition knowledge (using a validated 143-item questionnaire), cooking and food skills (using 14- and 19-item scales, respectively), and eight eating behaviours (hunger, food responsiveness, emotional overeating, enjoyment of food, satiety responsiveness, emotional undereating, food fussiness, and slowness in eating, using the 35-item Adult Eating Behavior Questionnaire). HPF consumption was estimated using a validated brief diet history questionnaire. The associations between HPF consumption and age, body mass index, energy intake, and each score on food choice values and food literacy were evaluated by multiple linear regression. RESULTS: In males, one standard deviation increase in scores for cooking skill and satiety responsiveness was associated with an increase in HPF consumption by 22.1 g/4184 kJ (95% confidence interval (CI): 6.6 to 37.5) and 15.4 g/4184 kJ (95% CI: 6.0 to 24.7), respectively. In females, one standard deviation increase in age and scores for safety and nutrition knowledge corresponded to a decrease in HPF consumption by - 16.4 g/4184 kJ (95% CI: - 23.4 to - 9.3), - 9.9 g/4184 kJ (95% CI: - 19.1 to - 0.7), and - 11.1 g/4184 kJ (95% CI: - 17.0 to - 5.3), whereas one standard deviation increase in the satiety responsiveness score corresponded to an increase in HPF consumption by 13.1 g/4184 kJ (95% CI: 6.8 to 19.4). CONCLUSIONS: This cross-sectional study suggests that several aspects of food choice values and food literacy were associated with HPF consumption in Japanese adults. Further studies are needed to confirm our findings in a broader context.

The nutritional profile of commercial complementary foods in Japan: comparison between low- and high-price products.

Despite the increasing market share of commercial complementary foods, their nutritional characteristics and those associated with the price of products are still unknown in Japan. We compared the nutritional characteristics of commercially available complementary foods of different price levels in Japan. Data were obtained from the websites of Japanese brands of infant and young children's food. Nutrient profiles (unit/100 g), ingredients and food additives were compared between low- and high-priced products by product type. Sixty-three dry meals, 425 soft meals, 187 snacks and sweets, and 60 drinks were analysed. One-fifth of meals and snacks exceeded the CODEX-defined limit (200 mg Na/100 g). Most products lacked content information on nutrients non-mandated to be indicated. High-priced soft meals contained more protein (2·5 v. 1·9 g/100 g) and less Na (0·18 v. 0·46 g/100 g), less frequently used ≥ 1 added sugar (23 % v. 82 %), and less frequently used food additives than low-priced products; however, they had a lower variety of ingredients. The prevalence of products containing ≥ 1 added sugar was higher in low-priced snacks and sweets (91 % v. 77 %) but lower in drinks (48 % v. 84 %) than in their high-priced counterparts. High Na content is a concern among commercial complementary foods in Japan. Nonetheless, the relationship between the price and nutritional profile of these foods differs by product type. High-priced soft meals might be more favourable regarding nutrient content but not the variety of ingredients than low-priced counterparts. These findings elucidate the nutritional characteristics of commercial complementary foods in Japan.

Associations of food choice values and food literacy with overall diet quality: a nationwide cross-sectional study in Japanese adults.

To date, a limited number of studies have examined aspects of food choice values and food literacy in relation to some aspects of dietary behaviours. The aim of this cross-sectional study was to comprehensively examine the associations of food choice values and food literacy with diet quality. In total, 2231 Japanese adults aged 19-80 years completed questionnaires asking about food choice values (accessibility, convenience, health/weight control, tradition, sensory appeal, organic, comfort and safety) and food literacy characterised by nutrition knowledge, cooking skills, food skills and eating behaviours (hunger, food responsiveness, emotional overeating, enjoyment of food, satiety responsiveness, emotional undereating, food fussiness and slowness in eating). As a measure of diet quality, the Healthy Eating Index-2015 (HEI-2015) was calculated using a brief-type diet history questionnaire (BDHQ) or a food combination questionnaire (FCQ). In males, after adjustment for potential confounding factors (including age, BMI and the ratio of reported energy intake to estimated energy requirement), the HEI-2015 derived from BDHQ and that derived from FCQ were associated significantly (P ≤ 0·02) and positively with the food choice values of organic and inversely with food fussiness. In females, the HEI-2015 showed positive associations with the food choice values of health/weight control, nutrition knowledge and cooking skills and an inverse association with food fussiness, irrespective of the dietary assessment questionnaire (P ≤ 0·03). In conclusion, this study suggests that several aspects of food choice values and food literacy were associated with diet quality, and the aspects related differed between males and females.

Strategies to Modulate MicroRNA Functions for the Treatment of Cancer or Organ Injury.

Cancer and organ injury-such as that occurring in the perioperative period, including acute lung injury, myocardial infarction, and acute gut injury-are among the leading causes of death in the United States and impose a significant impact on quality of life. MicroRNAs (miRNAs) have been studied extensively during the last two decades for their role as regulators of gene expression, their translational application as diagnostic markers, and their potential as therapeutic targets for disease treatment. Despite promising preclinical outcomes implicating miRNA targets in disease treatment, only a few miRNAs have reached clinical trials. This likely relates to difficulties in the delivery of miRNA drugs to their targets to achieve efficient inhibition or overexpression. Therefore, understanding how to efficiently deliver miRNAs into diseased tissues and specific cell types in patients is critical. This review summarizes current knowledge on various approaches to deliver therapeutic miRNAs or miRNA inhibitors and highlights current progress in miRNA-based disease therapy that has reached clinical trials. Based on ongoing advances in miRNA delivery, we believe that additional therapeutic approaches to modulate miRNA function will soon enter routine medical treatment of human disease, particularly for cancer or perioperative organ injury. SIGNIFICANCE STATEMENT: MicroRNAs have been studied extensively during the last two decades in cancer and organ injury, including acute lung injury, myocardial infarction, and acute gut injury, for their regulation of gene expression, application as diagnostic markers, and therapeutic potentials. In this review, we specifically emphasize the pros and cons of different delivery approaches to modulate microRNAs, as well as the most recent exciting progress in the field of therapeutic targeting of microRNAs for disease treatment in patients.

[How accurate are self-reported anthropometrics among the Japanese? A scoping review].

Objectives　Monitoring of obesity and underweight prevalence in general populations is crucial for the implementation of effective public health measures. Self-reported height and weight values are often used to assess the body mass index (BMI) in such epidemiological surveillance. However, it is known that using self-reported height and weight may underestimate the prevalence of obesity (BMI≥25 kg/m2), while its accuracy for underweight (BMI<18.5 kg/m2) prevalence is not well-understood. The aim of this study was to conduct a scoping review on the accuracy of self-reported anthropometrics in the Japanese population, where both obesity and underweight are prevalent.Methods　Using PubMed and CiNii Research, a literature search was conducted for studies published in English or Japanese by 2022 that were conducted in Japan and compared self-reported and measured height, weight, or/and BMI. The study design and mean reported errors (mean of reported values－mean of measured values) were extracted and tabulated, and differences by BMI categories were also considered.Results　A total of 17 studies, with 11 being published in English, were included in this review. These studies were conducted in nationwide cohort studies (n=4), local populations (n=4), workplaces (n=3), and educational institutions (n=6), with diverse age ranges (10-91 years) and sample sizes (<100 to >30,000). Although the degree of mean reporting error varied between studies, most of the studies reported that height was overreported, weight was underreported, and BMI was underestimated. In the three studies that reported mean reporting errors by BMI category, the direction of reporting error for height remained consistent across all body size categories, while weight and BMI were overreported and overestimated only among the underweight. Four studies in adults showed that 14.2-37.6% of actually obese individuals and 11.1-32.3% of underweight individuals were misclassified as 'normal range' (18.5≤BMI<25 kg/m2) based on self-reporting, while 0.8-5.4% and 1.2-4.1% of individuals actually within the normal range were misclassified as 'underweight' and 'obese' based on self-report, respectively.Conclusion　This study suggests that using BMI based on self-reported height and weight can underestimate the prevalence of both obesity and underweight in the Japanese population. These biases should be taken into consideration when using self-reported anthropometrics in epidemiological studies.

Targeting alveolar-specific succinate dehydrogenase A attenuates pulmonary inflammation during acute lung injury.

Acute lung injury (ALI) is an inflammatory lung disease, which manifests itself in patients as acute respiratory distress syndrome (ARDS). Previous studies have implicated alveolar-epithelial succinate in ALI protection. Therefore, we hypothesized that targeting alveolar succinate dehydrogenase SDH A would result in elevated succinate levels and concomitant lung protection. Wild-type (WT) mice or transgenic mice with targeted alveolar-epithelial Sdha or hypoxia-inducible transcription factor Hif1a deletion were exposed to ALI induced by mechanical ventilation. Succinate metabolism was assessed in alveolar-epithelial via mass spectrometry as well as redox measurements and evaluation of lung injury. In WT mice, ALI induced by mechanical ventilation decreased SDHA activity and increased succinate in alveolar-epithelial. In vitro, cell-permeable succinate decreased epithelial inflammation during stretch injury. Mice with inducible alveolar-epithelial Sdha deletion (Sdhaloxp/loxp SPC-CreER mice) revealed reduced lung inflammation, improved alveolar barrier function, and attenuated histologic injury. Consistent with a functional role of succinate to stabilize HIF, Sdhaloxp/loxp SPC-CreER experienced enhanced Hif1a levels during hypoxia or ALI. Conversely, Hif1aloxp/loxp SPC-CreER showed increased inflammation with ALI induced by mechanical ventilation. Finally, wild-type mice treated with intra-tracheal dimethlysuccinate were protected during ALI. These data suggest that targeting alveolar-epithelial SDHA dampens ALI via succinate-mediated stabilization of HIF1A. Translational extensions of our studies implicate succinate treatment in attenuating alveolar inflammation in patients suffering from ARDS.

Hypoxia-inducible factor-dependent induction of myeloid-derived netrin-1 attenuates natural killer cell infiltration during endotoxin-induced lung injury.

Sepsis and sepsis-associated lung inflammation significantly contribute to the morbidity and mortality of critical illness. Here, we examined the hypothesis that neuronal guidance proteins could orchestrate inflammatory events during endotoxin-induced lung injury. Through a targeted array, we identified netrin-1 as the top upregulated neuronal guidance protein in macrophages treated with lipopolysaccharide (LPS). Furthermore, we found that netrin-1 is highly enriched in infiltrating myeloid cells, particularly in macrophages during LPS-induced lung injury. Transcriptional studies implicate hypoxia-inducible factor HIF-1α in the transcriptional induction of netrin-1 during LPS treatment. Subsequently, the deletion of netrin-1 in the myeloid compartment (Ntn1loxp/loxp LysM Cre) resulted in exaggerated mortality and lung inflammation. Surprisingly, further studies revealed enhanced natural killer cells (NK cells) infiltration in Ntn1loxp/loxp LysM Cre mice, and neutralization of NK cell chemoattractant chemokine (C-C motif) ligand 2 (CCL2) reversed the exaggerated lung inflammation. Together, these studies provide functional insight into myeloid cell-derived netrin-1 in controlling lung inflammation through the modulation of CCL2-dependent infiltration of NK cells.

Trends in dietary salt sources in Japanese adults: data from the 2007-2019 National Health and Nutrition Survey.

Identifying trends in dietary salt sources is essential for effectively reducing salt/Na intake. This study aimed to examine the trends in dietary salt sources among Japanese adults using the 2007-2019 National Health and Nutrition Survey data collected from 95 581 adults aged ≥ 20 years. Dietary intake was estimated using the 1-d household-based dietary record. Foods reported as potential sources of salt intake in Japan and other countries were categorised into twenty-one groups. Salt intake for each food group was adjusted using the density method based on the energy intake. Trends in dietary salt intake based on food sources by sex and age groups (20-39 years, 40-59 years and ≥ 60 years) were analysed using the Joinpoint Regression Program. Salt intake for each age group in both men and women decreased from 2007 (5·3 g/1000 kcal-6·4 g/1000 kcal) to 2019 (4·9 g/1000 kcal-5·6 g/1000 kcal). The major dietary source of salt continued to be seasonings such as soya sauce and soyabean paste (approximately 70 %). Salt intake from seasonings decreased over time in adults aged ≥ 40 years but did not change in those aged 20-39 years. Additionally, a decreasing salt intake from unprocessed fish and shellfish and an increasing salt intake from unprocessed meat were observed across all age categories for both sexes. This study demonstrated that a strategy targeting different age groups may be needed to reduce salt consumption from seasonings among the Japanese population. Further studies on salt content in seasonings and continued monitoring of trends in dietary salt sources are required.

Morphological and histological changes in the urethra after intraurethral nonablative erbium YAG laser therapy: an experimental study in beagle dogs.

The purpose of this study was to investigate the morphological and histological changes in the urethra in beagle dogs after intraurethral Er:YAG laser irradiation in nonablative mode to confirm the safety of this therapy. Six 2-year-old healthy female virgin beagle dogs (13 ± 1.51 kg) were used in this study. The animals were divided into 2 groups: the sham group, which received sham treatment (n = 3) involving insertion of an intraurethral cannula and laser delivery handpiece into the urethra without laser irradiation, and the experimental group (n = 3), which received intraurethral Er:YAG laser irradiation. The laser irradiation parameters were set according to clinical criteria (4 mm spot size, 1.5 J/cm2, 1.4 Hz, and 4 pulses) in nonablative mode. All animals received three sequential sessions at 4-week intervals. Urethrography and urethroscopy were performed in the 12th week and 13th week, respectively, after the first treatment. After urethroscopy, the animals were sacrificed, and urethral tissue was harvested for histological investigations. All procedures were performed under general anesthesia (40 mg/kg 3% sodium pentobarbital, i.v.). Transforming growth factor ß1 (TGF-ß1) and α-smooth muscle actin (α-SMA) expression levels were measured to evaluate the biochemical characteristics of the scar. Urethral stricture was not found by urethrography or urethroscopy in either group. Urethral epithelium thickness and collagen expression under the urethral mucosa were significantly increased in the experimental group compared with the sham group. However, there were no significant differences in TGF-ß1 and α-SMA expression between the experimental group and sham group (p > 0.05). Urethral stricture is not found in beagle dogs after clinically relevant intraurethral nonablative mode Er:YAG laser irradiation. Proliferation of urethral collagen and the urethral mucosa may be one of the mechanisms by which urine leakage symptoms can be improved.

A Novel Animal Model of Emphysema Induced by Anti-Elastin Autoimmunity.

Loss of immune tolerance to self-antigens can promote chronic inflammation and disrupt the normal function of multiple organs, including the lungs. Degradation of elastin, a highly insoluble protein and a significant component of the lung structural matrix, generates proinflammatory molecules. Elastin fragments (EFs) have been detected in the serum of smokers with emphysema, and elastin-specific T cells have also been detected in the peripheral blood of smokers with emphysema. However, an animal model that could recapitulate T cell-specific autoimmune responses by initiating and sustaining inflammation in the lungs is lacking. In this study, we report an animal model of autoimmune emphysema mediated by the loss of tolerance to elastin. Mice immunized with a combination of human EFs plus rat EFs but not mouse EFs showed increased infiltration of innate and adaptive immune cells to the lungs and developed emphysema. We cloned and expanded mouse elastin-specific CD4+ T cells from the lung and spleen of immunized mice. Finally, we identified TCR sequences from the autoreactive T cell clones, suggesting possible pathogenic TCRs that can cause loss of immune tolerance against elastin. This new autoimmune model of emphysema provides a useful tool to examine the immunological factors that promote loss of immune tolerance to self.

Development, validation and utilisation of dish-based dietary assessment tools: a scoping review.

OBJECTIVE: To summarise the existing evidence of development, validation and current status of utilisation of dish-based dietary assessment tools. DESIGN: Scoping review. SETTING: Systematic search using PubMed and Web of Science. RESULTS: We identified twelve tools from seventy-four eligible publications. They were developed for Koreans (n 4), Bangladeshis (n 2), Iranians (n 1), Indians/Malays/Chinese (n 1), Japanese (n 3) and Chinese Americans (n 1). Most tools (10/12) were composed of a dish-based FFQ. Although the development process of a dish list varied among the tools, six studies classified mixed dishes based on the similarity of their characteristics such as food ingredients and cooking methods. Tools were validated against self-reported dietary information (n 9) and concentration biomarkers (n 1). In the eight studies assessing the differences between the tool and a reference, the mean (or median) intake of energy significantly differed in five studies, and 26-83 % of nutrients significantly differed in eight studies. Correlation coefficients for energy ranged from 0·15 to 0·87 across the thirteen studies, and the median correlation coefficients for nutrients ranged from 0·12 to 0·77. Dish-based dietary assessment tools were used in fifty-nine studies mainly to assess diet-disease relationships in target populations. CONCLUSIONS: Dish-based dietary assessment tools have exclusively been developed and used for Asian-origin populations. Further validation studies, particularly biomarker-based studies, are needed to assess the applicability of tools.

Neuronal modulation of hepatic lipid accumulation induced by bingelike drinking.

Excessive alcohol consumption, including binge drinking, is a common cause of fatty liver disease. Binge drinking rapidly induces hepatic steatosis, an early step in the pathogenesis of chronic liver injury. Despite its prevalence, the process by which excessive alcohol consumption promotes hepatic lipid accumulation remains unclear. Alcohol exerts potent effects on the brain, including hypothalamic neurons crucial for metabolic regulation. However, whether or not the brain plays a role in alcohol-induced hepatic steatosis is unknown. In the brain, alcohol increases extracellular levels of adenosine, a potent neuromodulator, and previous work implicates adenosine signaling as being important for the development of alcoholic fatty liver disease. Acute alcohol exposure also increases both the activity of agouti-related protein (AgRP)-expressing neurons and AgRP immunoreactivity. Here, we show that adenosine receptor A2B signaling in the brain modulates the extent of alcohol-induced fatty liver in mice and that both the AgRP neuropeptide and the sympathetic nervous system are indispensable for hepatic steatosis induced by bingelike alcohol consumption. Together, these results indicate that the brain plays an integral role in alcohol-induced hepatic lipid accumulation and that central adenosine signaling, hypothalamic AgRP, and the sympathetic nervous system are crucial mediators of this process.