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Background and Aims: Metabolomics is used to predict, diagnose, and monitor metabolic disorders but altered metabolomic signatures have also been reported in diverse diseases, including autoimmune disorders. However, the metabolomic profile in autoimmune hepatitis (AIH) has not been investigated in depth. Therefore, we investigated the metabolomic signature of AIH and its significance as a diagnostic and pathogenetic tool., Approach and Results: Metabolites in plasma samples from 50 patients with AIH at diagnosis, 43 healthy controls, 72 patients with primary biliary cholangitis (PBC), 26 patients with metabolic dysfunction-associated liver disease, and 101 patients with chronic viral hepatitis were determined by 1 H NMR (nuclear magnetic resonance) spectroscopy. Fifty-two metabolites were quantified, and metabolic pathway analysis was performed. Multivariate analysis revealed that AIH could be differentiated from healthy controls and each of the disease controls ( p <0.001). Fifteen metabolites differentiated AIH from disease controls (PBC+chronic viral hepatitis+metabolic dysfunction-associated liver disease) (95% sensitivity and 92% specificity). Ten distinct metabolic pathways were altered in AIH compared to disease controls. The metabolic pathway of branched-chain amino acids (lower valine, leucine, and isoleucine levels and their catabolic intermediates in PBC), methionine (lower methionine, 2-aminobutyrate, and 2-hydroxybutyrate levels in PBC), alanine-aspartate-glutamate (lower metabolites in PBC), and that of metabolites associated with gut microbiota (lower choline, betaine, and dimethylamine levels in PBC) were significantly different between AIH and PBC ( p <0.01)., Conclusions: 1 H NMR spectroscopy could be a promising novel tool to diagnose and study AIH pathogenesis as there is no need for much sample handling, is highly reproducible with high sensitivity and specificity, and low cost., (Copyright © 2024 American Association for the Study of Liver Diseases.)

Introduction: Lipoprotein(a) [Lp(a)] is a strong, genetically determined, pathogenetic factor of atherosclerotic cardiovascular disease (ASCVD). The aim of this post-hoc analysis was to compare the effect of hypolipidemic treatment on Lp(a) levels of patients with mixed hyperlipidemia., Material and Methods: We previously randomized patients with mixed hyperlipidemia (low-density lipoprotein [LDL-C] > 160 mg/dl and triglycerides > 200 mg/dl) to rosuvastatin monotherapy 40 mg/day (R group, n = 30) or rosuvastatin 10 mg/day combined with fenofibrate 200 mg/day (RF group, n = 30) or omega-3 fatty acids 2 g/day (RΩ group, n = 30). In the present post-hoc analysis, we included only the patients whose Lp(a) levels were assessed (16, 16 and 15 in the R, RF and RΩ groups, respectively). Lipid profile and Lp(a) were measured at baseline and after 3 months of treatment., Results: Significant reductions in total cholesterol, LDL-C, non-high-density lipoprotein-cholesterol (non-HDL-C) and triglyceride levels were observed in all groups. A significant increase in Lp(a) levels was noted in the R ( p = 0.017) and RF ( p = 0.029) groups, while no significant difference was seen in the RΩ group ( p = NS). Regarding Lp(a) elevations, no differences were found between groups. In the R group, a strong negative correlation between the changes in Lp(a) and LDL-C ( r = -0.500, p = 0.049) was observed, while a significant negative correlation between the changes in Lp(a) and triglycerides ( r = -0.531, p = 0.034) was noted in the RF group., Conclusions: Rosuvastatin and/or fenofibrate treatment increases Lp(a) levels in patients with mixed hyperlipidemia. Novel therapies should target Lp(a) level reduction to decrease the residual ASCVD risk in patients with mixed hyperlipidemia., Competing Interests: Theodosios D. Filippatos reports participation in advisory board for Lilly and lecture honoraria from Boehringer Ingelheim, Mylan, Astra Zeneca, Lilly, Recordati, Bausch Health, Servier, Viatris, Omega-Pharma and Innovis. Michael Kostapanos receives consultancy fees by GlaxoSmithKline (GSK) and Amarin Pharmaceuticals. He is also a Clinical Research Physician Director (as complementary worker by secondment) in the GSK Clinical Unit Cambridge. The remaining authors have no conflicts of interest to declare., (Copyright: © 2024 Termedia & Banach.)

Breast cancer (BC) is one of the most common cancers worldwide and a leading cause of cancer-related deaths among women. The escalating incidence of BC underscores the necessity of multi-level treatment. BC is a complex and heterogeneous disease involving many genetic, lifestyle, and environmental factors. Growing evidence suggests that nutrition intervention is an evolving effective prevention and treatment strategy for BC. In addition, the human microbiota, particularly the gut microbiota, is now widely recognized as a significant player contributing to health or disease status. It is also associated with the risk and development of BC. This review will focus on nutrition intervention in BC, including dietary patterns, bioactive compounds, and nutrients that affect BC prevention and therapeutic responses in both animal and human studies. Additionally, this paper examines the impacts of these nutrition interventions on modulating the composition and functionality of the gut microbiome, highlighting the microbiome-mediated mechanisms in BC. The combination treatment of nutrition factors and microbes is also discussed. Insights from this review paper emphasize the necessity of comprehensive BC management that focuses on the nutrition–microbiome axis. [ABSTRACT FROM AUTHOR]

Worldwide, diabetes mellitus (DM) and cardiovascular diseases (CVDs) represent serious health problems associated with unhealthy diet and sedentarism. Metabolic syndrome (MetS) is characterized by obesity, dyslipidemia, hyperglycemia, insulin resistance (IR) and hypertension. The mammalian target of rapamycin (mTOR) is a serine/threonine kinase with key roles in glucose and lipid metabolism, cell growth, survival and proliferation. mTOR hyperactivation disturbs glucose metabolism, leading to hyperglycemia and further to IR, with a higher incidence in the Western population. Metformin is one of the most used hypoglycemic drugs, with anti-inflammatory, antioxidant and antitumoral properties, having also the capacity to inhibit mTOR. mTOR inhibitors such as rapamycin and its analogs everolimus and temsirolimus block mTOR activity, decrease the levels of glucose and triglycerides, and reduce body weight. The link between mTOR dysregulation, IR, hypertension and mTOR inhibitors has not been fully described. Therefore, the main aim of this narrative review is to present the mechanism by which nutrients, proinflammatory cytokines, increased salt intake and renin–angiotensin–aldosterone system (RAAS) dysregulation induce mTOR overactivation, associated further with IR and hypertension development, and also mTOR inhibitors with higher potential to block the activity of this protein kinase. [ABSTRACT FROM AUTHOR]

Introduction: Pathogenesis of cutaneous leishmaniases involves parasite growth, persistent inflammation, and likely participation of lipoproteins (LP). The cholesteryl ester transfer protein (CETP), involved in LP remodeling, has been shown to participate in the inflammatory response and the evolution of infectious conditions. Methods: We evaluated the impact of the presence of CETP on infection by Leishmania (L.) amazonensis in an experimental model of cutaneous leishmaniasis using C57BL6/J mice transgenic for human CETP (CETP), having as control their littermates that do not express the protein, wild-type (WT) mice. The progression of the lesion after infection in the footpad was monitored for 12 weeks. Two groups of animals were formed to collect the plantar pad in the 4th and 12th week post-infection. Results: The lesion increased from the 3rd week onwards, in both groups, with a gradual decrease from the 10th week onwards in the CETP group compared to the WT group, showing a reduction in parasitism and an improvement in the healing process, a reduction in CD68+ cells, and an increase in CD163+ and CD206, characterizing a population of M2 macrophages. A reduction in ARG1+ cells and an increase in INOS+ cells were observed. During infection, the LP profile showed an increase in triglycerides in the VLDL fraction in the CETP group at 12 weeks. Gene expression revealed a decrease in the CD36 receptor in the CETP group at 12 weeks, correlating with healing and parasite reduction. In vitro, macrophages derived from bone marrow cells from CETP mice showed lower parasite load at 48 h and, a reduction in arginase activity at 4 h accompanied by increased NO production at 4 and 24 h compared to WT macrophages, corroborating the in vivo findings. Discussion: The data indicate that the presence of CETP plays an important role in resolving Leishmania (L.) amazonensis infection, reducing parasitism, and modulating the inflammatory response in controlling infection and tissue repair. [ABSTRACT FROM AUTHOR]

Aminoglycosides (AGs) represent a prominent class of antibiotics widely employed for the treatment of various bacterial infections. Their widespread use has led to the emergence of antibiotic-resistant strains of bacteria, highlighting the need for analytical methods that allow the simple and reliable determination of these drugs in pharmaceutical formulations and biological samples. In this study, a simple, robust and easy-to-use analytical method for the simultaneous determination of five common aminoglycosides was developed with the aim to be widely applicable in routine laboratories. With this purpose, different approaches based on liquid chromatography with direct UV spectrophotometric detection methods were investigated: on the one hand, the use of stationary phases based on hydrophilic interactions (HILIC); on the other hand, the use of reversed-phases in the presence of an ion-pairing reagent (IP-LC). The results obtained by HILIC did not allow for an effective separation of aminoglycosides suitable for subsequent spectrophotometric UV detection. However, the use of IP-LC with a C18 stationary phase and a mobile phase based on tetraborate buffer at pH 9.0 in the presence of octanesulfonate, as an ion-pair reagent, provided adequate separation for all five aminoglycosides while facilitating the use of UV spectrophotometric detection. The method thus developed, IP-LC-UV, was optimized and applied to the quality control of pharmaceutical formulations with two or more aminoglycosides. Furthermore, it is demonstrated here that this methodology is also suitable for more complex matrices, such as serum, which expands its field of application to therapeutic drug monitoring, which is crucial for aminoglycosides, with a therapeutic index ca. 50%. [ABSTRACT FROM AUTHOR]

Dyslipidemia and hepatic steatosis are the characteristics of the initial stage of nonalcohol fatty liver disease (NAFLD), which can be reversed by lifestyle intervention, including dietary supplementation. However, such commercial dietary supplements with solid scientific evidence and in particular clear mechanistic elucidation are scarce. Here, the health benefits of MHP, a commercial mulberry and Hippophae‐based solid beverage, were evaluated in NAFLD rat model and the underlying molecular mechanisms were investigated. Histopathologic examination of liver and white adipose tissue found that MHP supplementation reduced hepatic lipid accumulation and adipocyte hypertrophy. Serum biochemical results confirmed that MHP effectively ameliorated dyslipidemia and decreased circulation‐free fatty acid level. RNA‐Seq‐based transcriptomic analysis showed that MHP‐regulated genes are involved in the inhibition of lipolysis of adipose tissue and thus may contribute to the reduction of hepatic ectopic lipid deposition. Furthermore, MHP upregulated ACSL1–CPT1a–CPT2 pathway, a canonical pathway that regulated mitochondrial fatty acid metabolism, and promoted liver and adipose tissue fatty acid β‐oxidation. These results suggest that adipose tissue–liver crosstalk may play a key role in maintaining glucose and lipid metabolic hemostasis. In addition, MHP can also ameliorate chronic inflammation through regulating the secretion of adipokines. Our study demonstrates that MHP is able to improve dyslipidemia and hepatic steatosis through crosstalk between adipose tissue and liver and also presents transcriptomic evidence to support the underlying mechanisms of action, providing solid evidence for its health claims. [ABSTRACT FROM AUTHOR]

The hypothesis of this randomized controlled trial was that a clinical decision support system (CDSS) would increase adherence to the Mediterranean diet (MD) among adolescent females with polycystic ovary syndrome (PCOS). The objective was to assess the impact of personalized MD plans delivered via a CDSS on nutritional status and psychological well-being. Forty adolescent females (15–17 years) with PCOS were randomly assigned to the MD group (n = 20) or the Control group (n = 20). The MD group received personalized MD plans every 15 days via a CDSS, while the Control group received general nutritional advice. Assessments were conducted at baseline and after 3 months. Results showed significantly increased MD adherence in the MD group compared to the Control group (p < 0.001). The MD group exhibited lower intakes of energy, total fat, saturated fat, and cholesterol, and higher intakes of monounsaturated fat and fiber (p < 0.05). Serum calcium and vitamin D status (p < 0.05), as well as anxiety (p < 0.05) were improved. In conclusion, tailored dietary interventions based on MD principles, delivered via a CDSS, effectively manage PCOS in adolescent females. These findings highlight the potential benefits of using technology to promote dietary adherence and improve health outcomes in this population. ClinicalTrials.gov registry: NCT06380010. [ABSTRACT FROM AUTHOR]

This study was to investigate the effects of Smilax China L. saponins (SCS) on non-alcoholic fatty liver disease (NAFLD). Rats were fed a high-fat diet (HFD) for 8 weeks to induce NAFLD, followed by SCS treatment for 8 weeks. The effect of SCS on liver injury was observed by H&E staining and the regulative mechanism of SCS on lipid formation was exposed by detecting Oil red O, insulin resistance (IR), and fatty acids synthesis (FAS). Furthermore, transcriptomics and metabolomics were performed to analyze the potential targets. The experimental results indicated that SCS exerted a positive curative effect in alleviating HFD-induced overweight, hepatic injury, steatosis, and lipid formation and accumulation in rats, and the preliminary mechanism studies showed that SCS could alleviate IR, inhibit FAS expression, and reduce Acetyl-CoA levels. Besides, the integrative analysis of transcriptomics and metabolomics exposed the targets of SCS to regulate lipid production likely being the sphingolipid metabolism and glycerophospholipid metabolism pathways. This study demonstrates that SCS significantly ameliorates lipid metabolic disturbance in rats with NAFLD by relieving insulin resistance, inhibiting the FAS enzymes, and regulating the sphingolipid and glycerophospholipid metabolism pathways. [ABSTRACT FROM AUTHOR]

Objective. Lung cancer (LC) patients suffer from multiple cooccurring symptoms. Interventions that have the potential to impact more than one symptom within a symptom cluster should be identified. The aim of this review was to examine nonpharmacological interventions that were effective in the management of one or more of the following symptoms in LC patients: dyspnea, fatigue, physical functioning (PF), and role functioning (RF). Methods. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) was used for reporting this systematic review. The Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (using the PubMed interface), Embase (using the embase.com interface), and Web of Science were used as electronic databases. Randomized controlled studies were included if they assessed the effects of nonpharmacological interventions on dyspnea, fatigue, PF, and/or RF in patients with LC. Studies were evaluated with the Cochrane risk of bias tool, and relevant data were extracted and narratively summarized. Results and Conclusions. In total, 89 articles were included. Search results (until April 2023) show that most evidence was found for exercise interventions, followed by multicomponent, psychoeducational, diet, acupuncture, and other interventions. Studies that had an effect on multiple symptoms were observed to have the most frequent instances of positively affecting dyspnea, followed by PF, fatigue, and RF. [ABSTRACT FROM AUTHOR]

Simple Summary: Cancer-related fatigue is a common distressing complaint of breast cancer patients treated with chemotherapy. Nutritional quality plays a pivotal role in cancer-related fatigue, while increased interest towards new pharmacological agents has been observed. Melatonin, an endogenous hormone that regulates the human sleep–wake cycle, could alleviate cancer-related fatigue. In the present human trial, we investigated the effects of melatonin intake (i.e., 1 mg/day) vs. placebo on fatigue in women with active breast cancer over a period of 3 months. In both groups, nutritional advice regarding the Mediterranean diet was implemented. At the trial endpoint, the results showed that only patients receiving melatonin improved cancer-related fatigue compared to baseline. This implies that the oral supplementation of melatonin could ameliorate fatigue in breast cancer patients who undergo chemotherapy treatment. Cancer-related fatigue (CRF) is a common distressing complaint of breast cancer (BC) patients treated with chemotherapy. Nutritional quality plays a pivotal role in CRF, while increased interest towards new pharmacological agents has been observed. Melatonin, an endogenous hormone that regulates the human sleep–wake cycle, could alleviate CRF. In the present randomized, placebo-controlled 3-month trial, we investigated the effects of melatonin intake (i.e., 1 mg/day) vs. placebo in BC patients on CRF. In both arms, the Mediterranean diet (MD) was implemented. Medical history, anthropometry and blood withdrawal were performed. CRF was evaluated by the Functional Assessment of Chronic Illness Therapy—Fatigue questionnaire and MD adherence by the MedDietScore. In total, 49 BC women (median age 52 years) were recruited, namely N = 23 in the intervention arm and N = 26 in the placebo arm. At baseline, CRF was positively associated with body mass index (BMI), even when adjusted for age, waist circumference and blood indices related to disease prognosis (beta = −0.882, p = 0.003). At 3 months, both groups showed a BMI decrease (p < 0.05), but only the intervention group improved CRF compared to baseline (p = 0.003). No differences in CRF were observed between the groups. In conclusion, melatonin oral supplementation could ameliorate CRF in BC patients. [ABSTRACT FROM AUTHOR]

In preterm neonates unable to obtain sufficient oral nutrition, intravenous lipid emulsion is life-saving. The contribution of post-conceptional level of maturation to pathology that some neonates experience is difficult to untangle from the global pathophysiology of premature birth. In the present study, we determined fetal physiological responses to intravenous lipid emulsion. Fetal sheep were given intravenous Intralipid 20® (n = 4 females, 7 males) or Lactated Ringer's Solution (n = 7 females, 4 males) between 125 ± 1 and 133 ± 1 d of gestation (term = 147 d). Manufacturer's recommendation for premature human infants was followed: 0.5--1 g/kg/d initial rate, increased by 0.5--1 to 3 g/kg/d. Hemodynamic parameters and arterial blood chemistry were measured, and organs were studied postmortem. Red blood cell lipidomics were analyzed by LC-MS. Intravenous Intralipid did not alter hemodynamic or most blood parameters. Compared with controls, Intralipid infusion increased final day plasma protein (P=0.004; 3.5 ± 0.3 vs. 3.9 ± 0.2 g/dL), albumin (P = 0.031; 2.2 ± 0.1 vs. 2.4 ± 0.2 g/dL), and bilirubin (P<0.001; conjugated: 0.2 ± 0.1 vs. 0.6 ± 0.2 mg/dL; unconjugated: 0.2 ± 0.1 vs. 1.1 ± 0.4 mg/dL). Circulating IGF-1 decreased following Intralipid infusion (P<0.001; 66 ± 24 vs. 46 ± 24 ng/mL). Compared with control Oil Red O liver stains (median score 0), Intralipid-infused fetuses scored 108 (P=0.0009). Lipidomic analysis revealed uptake and processing of infused lipids into red blood cells, increasing abundance of saturated fatty acids. The near-term fetal sheep tolerates intravenous lipid emulsion well, although lipid accumulates in the liver. Increased levels of unconjugated bilirubin may reflect increased red blood cell turnover or impaired placental clearance. Whether Intralipid is less well tolerated earlier in gestation remains to be determined. [ABSTRACT FROM AUTHOR]

Purpose of Review: Coronary artery disease (CAD) in women is an evolving area of interest in cardiovascular medicine. This review seeks to provide a summary of contemporary insights into the gender-specific pathophysiology of CAD, particularly focusing on emerging risk factors and hormonal biology in women. In addition, we make our observations on gender differences in guideline-based management, highlighting the gaps in care and joining others in expounding the need for further research and gender-specific recommendations in the management of CAD. Recent Findings: Recent publications have brought into focus gender-based differences in the diagnosis and management of CAD with a demonstrable bias that adversely affects women. Since the recognition of such bias, contemporary clinical trials are designed to pay particular attention to equal representation in research studies as well as specifically evaluate gender-based outcomes. It has come to light that INOCA or ischemia with non-obstructive coronaries disproportionately affects women. Additionally, women are prone to more complications with interventions. Investigations are underway to understand the gender discrepancies better to address women's cardiovascular needs. There is a need for further studies to fully understand the unique hormonal biology and life stages of women, which affect coronary physiology. Additionally, socio-psychological factors that have a disproportionate influence on women need further study. Advances in cardiac imaging, particularly in coronary CT angiography and cardiac MRI, have the potential to accurately and non-invasively diagnose cardiovascular pathology so that care for women can be individualized in the era of precision medicine. Summary: Gender-specific care of women with cardiovascular disease starts early in life by recognizing the complex interplay between vascular and neuro-hormonal biology as well as psycho-social, environmental, and cultural factors. In this review, we discuss the less well-recognized risk factors, conditions prevalent in women that affect coronary biology, and the current management gaps in addressing the needs of women with CAD. [ABSTRACT FROM AUTHOR]

A subgroup of endocrine-disrupting chemicals have the ability to disrupt metabolism. These metabolism-disrupting chemicals (MDCs) can end up in aquatic environments and lead to adverse outcomes in fish. Although molecular and physiological effects of MDCs have been studied in adult fish, few studies have investigated the consequences of metabolic disruption in fish during the earliest life stages. To investigate the processes affected by metabolic disruption, zebrafish embryos were exposed to peroxisome proliferator-activated receptor gamma (PPARγ) agonist rosiglitazone, the PPARγ antagonist T0070907, and the well-known environmentally relevant MDC bisphenol A. Decreased apolipoprotein Ea transcript levels indicated disrupted lipid transport, which was likely related to the observed dose-dependent increases in yolk size across all compounds. Increased yolk size and decreased swimming activity indicate decreased energy usage, which could lead to adverse outcomes because the availability of energy reserves is essential for embryo survival and growth. Exposure to T0070907 resulted in a darkened yolk. This was likely related to reduced transcript levels of genes involved in lipid transport and fatty acid oxidation, a combination of responses that was specific to exposure to this compound, possibly leading to lipid accumulation and cell death in the yolk. Paraoxonase 1 (Pon1) transcript levels were increased by rosiglitazone and T0070907, but this was not reflected in PON1 enzyme activities. The present study shows how exposure to MDCs can influence biochemical and molecular processes involved in early lipid metabolism and may lead to adverse outcomes in the earliest life stages of fish. Environ Toxicol Chem 2024;43:1880-1893. © 2024 The Author(s). Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC., (© 2024 The Author(s). Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.)

Objective: To review the current scientific literature on renal tubular acidosis (RTA) in people and small animals, focusing on diseases in veterinary medicine that result in secondary RTA., Data Sources: Scientific reviews and original research publications on people and small animals focusing on RTA., Summary: RTA is characterized by defective renal acid-base regulation that results in normal anion gap hyperchloremic metabolic acidosis. Renal acid-base regulation includes the reabsorption and regeneration of bicarbonate in the renal proximal tubule and collecting ducts and the process of ammoniagenesis. RTA occurs as a primary genetic disorder or secondary to disease conditions. Based on pathophysiology, RTA is classified as distal or type 1 RTA, proximal or type 2 RTA, type 3 RTA or carbonic anhydrase II mutation, and type 4 or hyperkalemic RTA. Fanconi syndrome comprises proximal RTA with additional defects in proximal tubular function. Extensive research elucidating the genetic basis of RTA in people exists. RTA is a genetic disorder in the Basenji breed of dogs, where the mutation is known. Secondary RTA in human and veterinary medicine is the sequela of diseases that include immune-mediated, toxic, and infectious causes. Diagnosis and characterization of RTA include the measurement of urine pH and the evaluation of renal handling of substances that should affect acid or bicarbonate excretion., Conclusions: Commonality exists between human and veterinary medicine among the types of RTA. Many genetic defects causing primary RTA are identified in people, but those in companion animals other than in the Basenji are unknown. Critically ill veterinary patients are often admitted to the ICU for diseases associated with secondary RTA, or they may develop RTA while hospitalized. Recognition and treatment of RTA may reverse tubular dysfunction and promote recovery by correcting metabolic acidosis., (© Veterinary Emergency and Critical Care Society 2024.)

Purpose: Obesity can increase mortality and morbidity in breast cancer survivors. Healthy lifestyle factors such as diet can help manage weight in this population. This systematic review examined lifestyle interventions with dietary strategies for breast cancer survivors and their effect on diet and/or weight-related outcomes., Methods: Searches were conducted in Ovid MEDLINE ® ALL (1946-February 14, 2022), Embase (Elsevier), CINAHL Complete (EBSCO), and APA PsycArticles (EBSCO), using keywords for diet, breast cancer, and intervention. The search was limited to human studies, English language, and publication processing date 2016-2023., Results: The search yielded 3427 articles. After title and abstract review, 225 full-text articles were screened, and 67 articles with 61 distinct samples and interventions met inclusion criteria. Of these 61 lifestyle interventions with dietary strategies, 43 interventions also addressed physical activity. Most studies were randomized controlled trials (n = 41) and conducted post-treatment (n = 45). Mean participant age was 54 years. Of 29 studies that reported race/ethnicity, 20 (69%) reported ≥50% White participants. Of 36 that reported dietary outcomes, 29 (81%) reported significant findings. Of 57 that reported weight-related outcomes, 51 (89%) reported significant findings., Conclusion: This review demonstrated promising evidence for the efficacy of lifestyle interventions with dietary strategies in breast cancer survivors. However, culturally tailored interventions and interventions conducted before and during treatment are lacking., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Pre-eclampsia is a complex multi-system pregnancy disorder with limited treatment options. Therefore, we aimed to screen for metabolites that have causal associations with preeclampsia and to predict target-mediated side effects based on Mendelian randomization (MR) analysis. A two-sample MR analysis was firstly conducted to systematically assess causal associations of blood metabolites with pre-eclampsia, by using metabolites related large-scale genome-wide association studies (GWASs) involving 147,827 European participants, as well as GWASs summary data about pre-eclampsia from the FinnGen consortium R8 release data that included 182,035 Finnish adult female subjects (5922 cases and 176,113 controls). Subsequently, a phenome-wide MR (Phe-MR) analysis was applied to assess the potential on-target side effects associated with hypothetical interventions that reduced the burden of pre-eclampsia by targeting identified metabolites. Four metabolites were identified as potential causal mediators for pre-eclampsia by using the inverse-variance weighted method, including cholesterol in large HDL (L-HDL-C) [odds ratio (OR): 0.88; 95% confidence interval (95% CI): 0.83-0.93; P = 2.14 × 10 -5 ), cholesteryl esters in large HDL (L-HDL-CE) (OR: 0.88; 95% CI: 0.83-0.94; P = 5.93 × 10 -5 ), free cholesterol in very large HDL (XL-HDL-FC) (OR: 0.88; 95% CI: 0.82-0.94; P = 1.10 × 10 -4 ) and free cholesterol in large HDL (L-HDL-FC) (OR: 0.89; 95% CI: 0.84-0.95; P = 1.45 × 10 -4 ). Phe-MR analysis showed that targeting L-HDL-CE had beneficial effects on the risk of 24 diseases from seven disease chapters. Based on this systematic MR analysis, L-HDL-C, L-HDL-CE, XL-HDL-FC, and L-HDL-FC were inversely associated with the risk of pre-eclampsia. Interestingly, L-HDL-CE may be a promising drug target for preventing pre-eclampsia with no predicted detrimental side effects. The study consists of a two-stage design that conducts MR at both stages. First, we assessed the causality for the associations between 194 blood metabolites and the risk of pre-eclampsia. Second, we investigated a broad spectrum of side effects associated with the targeting identified metabolites in 693 non-preeclampsia diseases. Our results suggested that Cholesteryl esters in large HDL may serve as a promising drug target for the prevention or treatment of pre-eclampsia with no predicted detrimental side effects., (© 2024. The Author(s), under exclusive licence to The Japanese Society of Hypertension.)

Background: Elevated concentrations of serum uric acid (SUA) are associated with several conditions, including cardiovascular disease. The present study aimed to estimate the impact of statin therapy on SUA levels through a systematic review and meta-analysis of clinical trials., Methods: PubMed, Embase, Web of Science, and Scopus were searched on January 14, 2022, to identify eligible clinical trials. The intervention group received statins as monotherapy or in combination with other drugs, and the control group received non-statins or placebo. Studies reporting SUA levels before and after treatment were selected for further analysis. Finally, the data were pooled, and the mean changes in SUA, total cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL), and triglycerides were reported., Results: Out of 1269 identified studies, 23 were included in the review. A total of 3928 participants received statin therapy, and 1294 were included in control groups. We found a significant reduction in SUA levels following statin therapy (mean difference (MD) = -26.67 μmol/L with 95% confidence interval (CI) [-44.75, -8.60] (P =0.004)). Atorvastatin (MD = -37.93 μmol/L [-67.71, -8.15]; P < 0.0001), pravastatin (MD = -12.64 μmol/L [-18.64, -6.65]; P < 0.0001), and simvastatin (MD = -5.95 μmol/L [-6.14, -5.80]; P < 0.0001), but not rosuvastatin, were significantly associated with a reduction in SUA levels. An analysis comparing different types of statins showed that pravastatin 20-40 mg/day could significantly reduce SUA when compared to simvastatin 10-20 mg/day (-21.86 μmol/L [-36.33,-7.39]; P =0.003)., Conclusion: Statins were significantly associated with a decrease in SUA levels, particularly atorvastatin, which was found to be most effective in lowering SUA. Atorvastatin may be the most appropriate cholesterol-lowering agent for patients with or at risk of hyperuricemia., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)