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Background Pregnant women with chronic hepatitis B (CHB) exhibit unique clinical features in terms of postpartum immune system reconstitution and recovery from pregnancy-related changes. However, current studies focus primarily on the outcomes of maternal–infant transmission and postpartum hepatitis flares. We aimed to evaluate the profiles of hepatitis B core-related antigen (HBcrAg) and pregenomic RNA (pgRNA) in pregnant women with CHB. Methods This retrospective analysis included treatment-naïve pregnant women with CHB who were followed up regularly in an outpatient clinic from 2014 to 2021. Baseline HBcrAg and pgRNA levels were compared in patients with different disease phases. Changes in these parameters were examined in a subset of patients receiving antiviral prophylaxis. HBcrAg and pgRNA levels were measured before treatment, at 32 weeks of gestation, and postpartum. Results The final analysis included a total of 121 patients, 100 of whom were hepatitis B e antigen (HBeAg)–positive (96 and 4 in the immune-tolerant and -indeterminate phases, respectively) and 21 of whom were HBeAg-negative (6 and 15 in the immune-active and -inactive carrier phases, respectively). The HBeAg-negative group vs the HBeAg-positive group had lower levels of baseline HBcrAg (median [interquartile range {IQR}], 3.7 [3.0–5.9] vs 8.6 [8.4–8.7] log10 U/mL; P <.01) and pgRNA (median [IQR], 0.0 [0.0–2.5] vs 7.8 [7.6–8.1] log10 copies/mL; P <.01). The serum levels of HBcrAg and pgRNA were highest in immune-tolerant carriers and lowest in immune-inactive carriers. In HBeAg-positive patients, the correlation coefficients of HBcrAg and pgRNA with hepatitis B virus (HBV) DNA were 0.40 and 0.43, respectively; in HBeAg-negative patients, they were 0.53 and 0.51, respectively (all P <.05). The correlation coefficients with hepatitis B surface antigen (HBsAg) were 0.55 and 0.52 (P <.05) in HBeAg-positive patients, respectively, while in HBeAg-negative patients they were 0.42 and 0.37, respectively (P >.05). Among 96 patients receiving antiviral prophylaxis, we detected a rapid decrease in HBV DNA to an undetectable level during treatment but relatively stable levels of pgRNA and HBcrAg. Conclusions HBcrAg and pgRNA levels are lower in HBeAg-negative patients than in HBeAg-positive patients. These 2 markers are significantly associated with HBV DNA irrespective of HBeAg status, while they are significantly associated with HBsAg only in HBeAg-positive patients. [ABSTRACT FROM AUTHOR]

Whether ultra‐processed food consumption is associated with the risk of pancreatic cancer has not been determined. We performed a prospective study to fill this gap. A population‐based cohort of 98 265 American adults was identified from the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. Ultra‐processed foods were defined by the NOVA classification. Cox regression was used to estimate hazard ratios (HRs) for pancreatic cancer incidence. Subgroup analysis was performed to identify the potential effect modifiers. During a mean follow‐up of 8.86 years, 387 pancreatic cancer cases occurred. High consumption of ultra‐processed foods was found to be associated with an increased risk of pancreatic cancer (fully adjusted HRquartile 4 vs 1:1.49; 95% confidence interval [CI]: 1.07‐2.07; Ptrend =.021) in a linear dose‐response manner (Pnonlinearity =.075). Subgroup analysis further found that the positive association of ultra‐processed food consumption with the risk of pancreatic cancer was more pronounced in subjects aged <65 years (HRquartile 4 vs 1:2.17; 95% CI: 1.14‐4.15) than in those aged ≥65 years (HRquartile 4 vs 1:1.32; 95% CI: 0.88‐1.94), though the interaction test failed to achieve the statistical significance (Pinteraction =.061). These findings suggest that reducing ultra‐processed food consumption may be beneficial in decreasing pancreatic cancer incidence. [ABSTRACT FROM AUTHOR]

We aimed to examine whether type 2 diabetes–prevention diet, a dietary pattern previously developed for reducing type 2 diabetes risk, was associated with mortality in a US population. A population-based cohort of 86,633 subjects was identified from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (1993–2015). Dietary information was collected with a food frequency questionnaire. A dietary diabetes risk-reduction score was calculated to reflect adherence to this dietary pattern, with higher scores representing better adherence. Hazard ratios (HRs) and absolute risk differences (ARDs) in mortality rates per 10,000 person-years were calculated. After a mean follow-up of 13.6 years, 17,532 all-cause deaths were observed. Participants with the highest versus the lowest quintiles of dietary diabetes risk-reduction score were observed to have decreased risks of death from all causes (HR = 0.76, 95% CI: 0.72, 0.80; ARD: −81.94, 95% CI: −93.76, −71.12), cardiovascular disease (HR = 0.73, 95% CI: 0.66, 0.81; ARD: −17.82, 95% CI: −24.81, −11.30), and cancer (HR = 0.85, 95% CI: 0.78, 0.94; ARD: −9.92, 95% CI: −15.86, −3.59), which were modified by sex, smoking status, or alcohol consumption in subgroup analyses (P for interaction < 0.05 for all). In conclusion, a type 2 diabetes–prevention diet confers reduced risks of death from all causes, cardiovascular disease, and cancer in this US population. [ABSTRACT FROM AUTHOR]

Stress-adaptive mechanisms enabling cancer cells to survive under glucose deprivation remain elusive. N 6 -methyladenosine (m 6 A) modification plays important roles in determining cancer cell fate and cellular stress response to nutrient deficiency. However, whether m 6 A modification functions in the regulation of cancer cell survival under glucose deprivation is unknown. Here, we found that glucose deprivation reduced m 6 A modification levels. Increasing m 6 A modification resulted in increased hepatoma cell necrosis under glucose deprivation, whereas decreasing m 6 A modification had an opposite effect. Integrated m 6 A-seq and RNA-seq revealed potential targets of m 6 A modification under glucose deprivation, including the transcription factor FOSL1; further, glucose deprivation upregulated FOSL1 by inhibiting FOSL1 mRNA decay in an m 6 A-YTHDF2-dependent manner through reducing m 6 A modification in its exon1 and 5'-UTR regions. Functionally, FOSL1 protected hepatoma cells against glucose deprivation-induced necrosis in vitro and in vivo. Mechanistically, FOSL1 transcriptionally repressed ATF3 by binding to its promoter. Meanwhile, ATF3 and MAFF interacted via their leucine zipper domains to form a heterodimer, which competed with NRF2 for binding to antioxidant response elements in the promoters of NRF2 target genes, thereby inhibiting their transcription. Consequently, FOSL1 reduced the formation of the ATF3-MAFF heterodimer, thereby enhancing NRF2 transcriptional activity and the antioxidant capacity of glucose-deprived-hepatoma cells. Thus, FOSL1 alleviated the necrosis-inducing effect of glucose deprivation-induced reactive oxygen species accumulation. Collectively, our study uncovers the protective role of m 6 A-FOSL1-ATF3 axis in hepatoma cell necrosis under glucose deprivation, and may provide new targets for cancer therapy., (© 2024. The Author(s), under exclusive licence to ADMC Associazione Differenziamento e Morte Cellulare.)