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Background: The surge in digital media consumption, coupled with the ensuing consequences of digital addiction, has witnessed a rapid increase, particularly after the initiation of the COVID-19 pandemic. Despite some studies exploring specific technological addictions, such as internet or social media addiction, in Bangladesh, there is a noticeable gap in research focusing on digital addiction in a broader context. Thus, this study aims to investigate digital addiction among students taking the university entrance test, examining its prevalence, contributing factors, and geographical distribution using GIS techniques., Methods: Data from a cross-sectional survey were collected from a total of 2,157 students who were taking the university entrance test at Jahangirnagar University, Bangladesh. A convenience sampling method was applied for data collection using a structured questionnaire. Statistical analyses were performed with SPSS 25 Version and AMOS 23 Version, whereas ArcGIS 10.8 Version was used for the geographical distribution of digital addiction., Results: The prevalence of digital addiction was 33.1% (mean score: 16.05 ± 5.58). Those students who are attempting the test for a second time were more likely to be addicted (42.7% vs. 39.1%), but the difference was not statistically significant. Besides, the potential factors predicted for digital addiction were student status, satisfaction with previous mock tests, average monthly expenditure during the admission test preparation, and depression. No significant difference was found between digital addiction and districts. However, digital addiction was higher in the districts of Manikganj, Rajbari, Shariatpur, and Chittagong Hill Tract areas, including Rangamati, and Bandarban., Conclusions: The study emphasizes the pressing need for collaborative efforts involving educational policymakers, institutions, and parents to address the growing digital addiction among university-bound students. The recommendations focus on promoting alternative activities, enhancing digital literacy, and imposing restrictions on digital device use, which are crucial steps toward fostering a healthier digital environment and balanced relationship with technology for students., (© 2024. The Author(s).)

Background: Acute myocardial infarction (AMI) is the top cause of death in Maldives. Our study aims to determine the prehospital delay and its associated factors in AMI patients in Maldives., Methods: A cross-sectional study was conducted with 127 patients, divided into early (≤ 6 h) and delayed (> 6 h) presenters to the hospital. The data collection for the study was carried out by interviewing AMI patients, focusing on their socio-demographic characteristics, coronary artery disease risk factors, clinical symptoms, situational factors, and behavioral and cognitive responses to symptoms., Results: The median onset-to-door time was 230 (IQR 420) minutes. The mean age of AMI patients was 50.9 (SD ± 12.9) years old, and 39.4% of them had delayed presentation to the hospital. Smokers (adj OR = 0.3; 95% CI: 0.1, 0.9; P = 0.047) and those with previous episodes of chest pain or AMI (adj OR = 0.2; 95% CI: 0.03, 0.91; P = 0.038) were significant factors for early presentation to the hospital, while denial of symptoms (adj OR = 29.3; 95% CI: 1.6, 547.2; P = 0.024) and lack of knowledge (adj OR = 7.2; 95% CI: 1.77, 29.43; P = 0.006) led to a delayed decision to seek treatment. Situational factors such as onset at the workplace (adj OR = 5.8; 95% CI: 1.24, 26.83; P = 0.025) had lower odds of delay, whereas referral cases (adj OR = 7.7; 95% CI: 1.9, 30.94; P = 0.004) and use of sea ambulance (adj OR = 11.1; 95% CI: 2.8, 43.8; P = 0.001) were prone to delay in presentation to the hospital., Conclusion: Sea ambulance, referral cases, lack of knowledge, and denial of symptoms are significant factors associated with prehospital delay among patients with AMI. Public awareness about the benefits of early presentation and improvement of the means of transportation between islands is suggested to improve emergency cardiac care in the country., (© 2023. The Author(s).)

Background: Microsomal triglyceride transfer protein (MTP) is essential for the assembly of lipoproteins. MTP has been shown on the surface of lipid droplets of adipocytes; however its function in adipose tissue is not well defined. We hypothesized that MTP may play critical role in adipose lipid droplet formation and expansion., Methods: Plasmids mediated overexpression and siRNA mediated knockdown of Mttp gene were performed in 3T3-L1 pre-adipocytes to evaluate the effects of MTP on cell differentiation and triglyceride accumulation. Adipose-specific knockdown of MTP was achieved in mice bybreeding MTP floxed (Mttp (fl/fl) ) mice with aP2-Cre recombinase transgenic mice. Adipose-specific MTP deficient (A-Mttp (-/-) ) mice were fed 60 % high-fat diet (HFD), and the effects of MTP knockdown on body weight, body fat composition, plasma and tissues lipid composition, glucose metabolism, lipogenesis and intestinal absorption was studied. Lipids were measured in total fasting plasma and size fractionated plasma using colorimetric assays. Gene expression was investigated by Real-Time quantitative PCR. All data was assessed using t-test, ANOVA., Results: MTP expression increased during early differentiation in 3T3-L1 cells, and declined later. The increases in MTP expression preceded PPARγ expression. MTP overexpression enhanced lipid droplets formation, and knockdown attenuated cellular lipid accumulation. These studies indicated that MTP positively affects adipogenesis. The ablation of the Mttp gene using aP2-Cre (A-Mttp (-/-) ) in mice resulted in a lean phenotype when fed a HFD. These mice had reduced white adipose tissue compared with wild-type Mttp (fl/fl) mice. The adipose tissue of A-Mttp (-/-) mice had increased number of smaller size adipocytes and less macrophage infiltration. Further, these mice were protected from HFD-induced fatty liver. The A-Mttp (-/-) mice had moderate increase in plasma triglyceride, but normal cholesterol, glucose and insulin levels. Gene expression analysis showed that the adipose tissue of the A-Mttp (-/-) mice had significantly lower mRNA levels of PPARγ and its downstream targets., Conclusion: These data suggest that MTP might modulate adipogenesis by influencing PPARγ expression, and play a role in the accretion of lipids to form larger lipid droplets. Thus, agents that inactivate adipose MTP may be useful anti-obesity drugs.

Background: Site-1 protease (S1P) is the key enzyme required for activation of the sterol regulatory element binding proteins (SREBPs) that govern lipid synthesis. While S1P has been speculated to influence plasma apoB-containing lipoprotein (Blp) metabolism, there has been little investigative work. LDL receptor (LDLR) is the major receptor for clearing plasma LDL cholesterol (LDL-c). Proprotein convertase subtilisin kexin type 9 (PCSK9) modulates LDL-c through post-translational degradation of the LDLR., Methods: A hepatic-specific knockdown (KD) of S1P was achieved using floxed S1P mouse models (S1P(f/f) and LDLR(-/-)S1P(f/f)) and hepatic expression of Cre recombinase. Lipids were measured in total plasma and size fractionated plasma using colorimetric assays. Realtime polymerase chain reaction, western blotting and ELISA were used to determine hepatic expression of key genes/protein. Plasmid mediated overexpression and siRNA mediated knockdown of genes were performed in mouse primary hepatocytes to determine the mechanistic basis of PCSK9 gene regulation., Results: A hepatic-specific KD of S1P resulted in a 45 % and 38 % reduction in plasma total cholesterol and triglyceride levels, respectively. Hepatic S1P KD had a minimal effect on plasma Blp cholesterol (Blp-c) in S1P(f/f) mice, despite significantly reducing VLDL secretion. Notably, hepatic S1P KD decreased the LDL receptor (LDLR) mRNA expression by 50 %. However, the reduction in LDLR protein levels was less than that of mRNA expression, especially under fed conditions. Further assessment of hepatic S1P deficiency revealed that it increased LDLR protein stability in vivo. Mechanistically, hepatic S1P KD was shown to decrease the liver and plasma levels of the protein proprotein convertase subtilisin/kexin type 9 (PCSK9), which degrades LDLR protein. This effect was more prominent in the fed condition and sufficient to account for the discordance in LDLR mRNA and protein levels. Furthermore, hepatic S1P was shown to regulate PCSK9 expression through activation of the SREBPs. In the LDLR(-/-) background, hepatic S1P KD significantly reduced Blp-c levels., Conclusion: Hepatic S1P is a physiological modulator of plasma Blp metabolism through its regulation of LDLR and PCSK9. Hepatic S1P is a valid target for lowering plasma Blp-c levels in the situation where LDLR function is compromised.

Nutrition & Metabolism has grown considerably in the ten years since its first article was published. To see how papers published in the journal had an impact we have identified some of the most popular articles in order to measure their influence, observe which fields are important to our readers, and try to explain what made these articles Nutrition & Metabolism "Classics".

Microsomal triglyceride transfer protein (MTTP) is an essential chaperone that assists in the assembly of apolipoprotein B-containing lipoproteins to transport lipids. We have shown that microRNA (miR)-30c regulates MTTP expression but other members of the same family do not. Further, we showed that interactions between miR-30c seed sequence and the 3΄-untranslated region (UTR) of the MTTP mRNA are critical for this regulation. The same seed sequence is shared by all the members of the miR-30 family. Therefore, it is unclear why only miR-30c regulates MTTP expression. Bioinformatics analysis revealed that, miR-30c interacts with MTTP mRNA involving supplementary site, besides seed sequence, forming an intervening loop. Here, we evaluated the importance of the supplementary site and the size of the intervening loop in miR-30c/MTTP mRNA interactions by cloning MTTP 3΄-UTR at the end of the luciferase gene and subjecting it to site-directed mutagenesis. Reducing the number of base pairs at the supplementary site abolished the ability of miR-30c to reduce luciferase activity. However, increasing the number of base pairs at the supplementary site, seed sequence or in the intervening loop enhanced the efficacy of miR-30c in reducing luciferase activity. These studies demonstrated that the supplementary site of miR-30c is, but the intervening loop is not, critical for binding to the MTTP mRNA. To our knowledge, this is the first demonstration that miRs might require both seed and supplementary interactions to regulate target mRNA specificity. Further, this study suggests that more potent miR-30c mimics could be synthesized by increasing base pairing in the loop region.

It has been reported that phospholipid transfer protein (PLTP) is an independent risk factor for human coronary artery disease. In mouse models, it has been demonstrated that PLTP overexpression induces atherosclerosis, while its deficiency reduces it. PLTP is considered a promising target for pharmacological intervention to treat atherosclerosis. However, we must still answer a number of questions before its pharmaceutical potential can be fully explored. In this review, we summarized the recent progresses made in the PLTP research field and focused on its effect on apoB-containing- triglyceride-rich particle and HDL metabolism.

Sphingolipids are ubiquitous and critical components of biological membranes. Their biosynthesis starts with soluble precursors in the endoplasmic reticulum and culminates in the Golgi complex and plasma membrane. Ceramides are important intermediates in the biosynthesis of sphingolipids, such as sphingomyelin, and their overload in the membranes is injurious to cells. The major product of ceramide metabolism is sphingomyelin. We observed that sphingomyelin synthase (SMS) 1 or SMS2 deficiencies significantly decreased plasma and liver sphingomyelin levels. However, SMS2 but not SMS1 deficiency increased plasma ceramides. Surprisingly, SMS1 deficiency significantly increased glucosylceramide and ganglioside GM3, but SMS2 deficiency did not. To explain these unexpected findings about modest to no significant changes in ceramides and increases in other sphingolipids after the ablation of SMS1, we hypothesize that cells have evolved several organelle specific mechanisms to maintain ceramide homeostasis. First, ceramides in the endoplasmic reticulum membranes are controlled by its export to Golgi by protein mediated transfer. Second, in the Golgi, ceramide levels are modulated by their enzymatic conversion to different sphingolipids such as sphingomyelin, and glucosylceramides. Additionally, these sphingolipids can become part of triglyceride-rich apolipoprotein B-containing lipoproteins and be secreted. Third, in the plasma membrane ceramide levels are maintained by ceramide/sphingomyelin cycle, delivery to lysosomes, and efflux to extracellular plasma acceptors. All these pathways might have evolved to ensure steady cellular ceramide levels.

Microsomal triglyceride transfer protein (MTP) was first identified as a major cellular protein capable of transferring neutral lipids between membrane vesicles. Its role as an essential chaperone for the biosynthesis of apolipoprotein B (apoB)-containing triglyceride-rich lipoproteins was established after the realization that abetalipoproteinemia patients carry mutations in the MTTP gene resulting in the loss of its lipid transfer activity. Now it is known that it also plays a role in the biosynthesis of CD1, glycolipid presenting molecules, as well as in the regulation of cholesterol ester biosynthesis. In this review, we will provide a historical perspective about the identification, purification and characterization of MTP, describe methods used to measure its lipid transfer activity, and discuss tissue expression and function. Finally, we will review the role MTP plays in the assembly of apoB-lipoprotein, the regulation of cholesterol ester synthesis, biosynthesis of CD1 proteins and propagation of hepatitis C virus. We will also provide a brief overview about the clinical potentials of MTP inhibition.

A new Open Access journal, Nutrition & Metabolism (N&M) will publish articles that integrate nutrition with biochemistry and molecular biology. The open access process is chosen to provide rapid and accessible dissemination of new results and perspectives in a field that is of great current interest. Manuscripts in all areas of nutritional biochemistry will be considered but three areas of particular interest are lipoprotein metabolism, amino acids as metabolic signals, and the effect of macronutrient composition of diet on health. The need for the journal is identified in the epidemic of obesity, diabetes, dyslipidemias and related diseases, and a sudden increase in popular diets, as well as renewed interest in intermediary metabolism.