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Hepatic proteomes are intricately controlled through biosynthesis, extracellular secretion, and intrahepatic degradation. Autophagy governs lysosome‐mediated intrahepatic degradation and the hepatic proteome. When autophagy is impaired, it leads to the accumulation of intrahepatic proteins, causing proteinopathy. This study investigates whether autophagy can modulate the hepatic proteome non‐degradatively. Utilizing conditional, inducible, and hepatotoxin models of hepatic autophagy impairment, we assessed the overall hepatic proteome expression using Coomassie brilliant blue (CBB) staining and liquid chromatography–tandem mass spectrometry (LC/MS). We pinpointed and confirmed four specific hepatic proteins—Cps1, Ahcy, Ca3, and Gstm1—that were selectively modified in autophagy‐deficient livers. Expression of Cps1, Ahcy, and Ca3 were significantly reduced, while Gstm1 expression increased in livers with autophagy impairment. Interestingly, these changes in hepatic protein levels were not due to defective autophagic degradation but were associated with alterations in mRNA transcript levels. Moreover, as a result of autophagic dysfunction, sustained activation of the nuclear erythroid‐derived 2‐like 2 (Nrf2) transcription factor, transcriptionally regulated the mRNA levels of these proteins. Our findings indicate that autophagy can influence hepatic proteins not solely via traditional degradative routes but also through non‐degradative transcriptional processes by modulating Nrf2.

At the time of breast cancer diagnosis, most patients meet the diagnostic criteria to be classified as obese or overweight. This can significantly impact patient outcome: breast cancer patients with obesity (body mass index > 30) have a poorer prognosis compared to patients with a lean BMI. Obesity is associated with hyperleptinemia, and leptin is a well-established driver of metastasis in breast cancer. However, the effect of hyperleptinemia on angiogenesis in breast cancer is less well-known. Angiogenesis is an important process in breast cancer because it is essential for tumor growth beyond 1mm3 in size as well as cancer cell circulation and metastasis. This review investigates the role of leptin in regulating angiogenesis, specifically within the context of breast cancer and the associated tumor microenvironment in obese patients.

Background. The Nepalese government announced a nationwide lockdown beginning on March 24, 2020 as an attempt to restrain the spread of COVID-19. The prohibition in flight operations and movement of vehicles, factory shutdowns and restriction in people's movement due to the lockdown led to a significant reduction in the amounts of pollutants degrading air quality in many countries. Objectives. The present study aimed to analyze changes in particulate matter (PM) emissions and the air quality index (AQI) of six cities in Nepal i.e., Damak, Simara, Kathmandu, Pokhara, Nepalgunj and Surkhet due to the nationwide lockdown in response to the COVID-19 outbreak. Methods. Daily PM concentrations of each of the six study cities from January 24 to September 21, 2020 were obtained from the World Air Quality Index project (https://aqicn.org) and analyzed using R Studio software. The drop percentage was calculated to determine the change in PM2.5 and PM10 concentration during different time periods. Independent sample Mann–Whitney U tests were performed to test the significance of differences in mean concentration for each site during the lockdown period (24 March–24 July 2020) and its corresponding period in 2019. Similarly, the significance of differences in mean concentrations between the lockdown period and the period immediately before lockdown (23 January–23 March) was also examined using the same test. Results. During the lockdown period, in overall Nepal, AQIPM2.5 and AQIPM10 were within the moderate zone for the maximum number of days. As a result of the lockdown, the highest immediate and final drop of PM2.5 was observed in Damak (26.37%) and Nepalgunj (80.86%), respectively. Similarly, the highest immediate drop of PM10 was observed in Surkhet (37.22%) and finally in Nepalgunj (81.14%). Analysis with the Mann–Whitney U test indicated that for both PM types, all sites showed a statistically significant (p < 0.05) difference in mean concentrations during lockdown and the corresponding period in 2019. Conclusions. The present study explored the positive association between vehicular movement and PM emissions, highlighting the need for alternative fuel sources to improve air quality and human health. Competing Interests. The authors declare no competing financial interests.

Hepatic proteomes are intricately controlled through biosynthesis, extracellular secretion, and intrahepatic degradation. Autophagy governs lysosome‐mediated intrahepatic degradation and the hepatic proteome. When autophagy is impaired, it leads to the accumulation of intrahepatic proteins, causing proteinopathy. This study investigates whether autophagy can modulate the hepatic proteome non‐degradatively. Utilizing conditional, inducible, and hepatotoxin models of hepatic autophagy impairment, we assessed the overall hepatic proteome expression using Coomassie brilliant blue (CBB) staining and liquid chromatography–tandem mass spectrometry (LC/MS). We pinpointed and confirmed four specific hepatic proteins—Cps1, Ahcy, Ca3, and Gstm1—that were selectively modified in autophagy‐deficient livers. Expression of Cps1, Ahcy, and Ca3 were significantly reduced, while Gstm1 expression increased in livers with autophagy impairment. Interestingly, these changes in hepatic protein levels were not due to defective autophagic degradation but were associated with alterations in mRNA transcript levels. Moreover, as a result of autophagic dysfunction, sustained activation of the nuclear erythroid‐derived 2‐like 2 (Nrf2) transcription factor, transcriptionally regulated the mRNA levels of these proteins. Our findings indicate that autophagy can influence hepatic proteins not solely via traditional degradative routes but also through non‐degradative transcriptional processes by modulating Nrf2. [ABSTRACT FROM AUTHOR]

BACKGROUND : Post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) is the most common and most serious complication of ERCP. Our aim was to estimate the nationwide incidence, temporal trends, and mortality of PEP in the United States and to establish risk factors associated with PEP development. METHODS : This was a retrospective cohort study analyzing Nationwide Inpatient Sample data from 2011 to 2017 using International Classification of Diseases codes. The primary outcomes were trends in PEP incidence and predictors of PEP development. Secondary outcomes were in-hospital mortality, length of hospital stay, and admission to the intensive care unit. RESULTS : Of 1 222 467 adult patients who underwent inpatient ERCP during the study period, 55 225 (4.5 %) developed PEP. The hospital admission rate of PEP increased by 15.3 %, from 7735 in 2011 to 8920 in 2017 (odds ratio [OR] 1.23, 95 % confidence interval [CI] 1.04 - 1.46; P = 0.02). The overall rate of mortality increased from 2.8 % of PEP cases in 2011 to 4.4 % in 2017 (OR 1.62, 95 %CI 1.10 - 2.38; P = 0.01). Multiple patient-related (alcohol use, cocaine use, obesity, chronic kidney disease, heart failure), procedure-related (therapeutic ERCP, sphincterotomy, pancreatic duct stent placement, sphincter of Oddi dysfunction), and hospital-related (teaching hospitals, hospitals located in the West and Midwest) factors that impact the occurrence of PEP were identified. CONCLUSIONS : Our study showed rising hospital admission and mortality rates associated with PEP in the United States. This calls for a greater recognition of this life-threatening complication and amelioration of its risk factors, whenever possible. [ABSTRACT FROM AUTHOR]