The other side of the incretin story: GIPR signaling in energy homeostasis.

Incretin receptor agonists have been effective in combatting obesity and diabetes. While the body of knowledge regarding the signaling mechanisms of glucagon-like peptide 1 (GLP-1) receptor agonists is ever-growing, glucose-dependent insulinotropic polypeptide receptor (GIPR) agonists are less understood. The previewed papers offer insight into the impact of adipose GIPR on energy and weight homeostasis.

Metabolic rewiring in skin epidermis drives tolerance to oncogenic mutations.

Skin epithelial stem cells correct aberrancies induced by oncogenic mutations. Oncogenes invoke different strategies of epithelial tolerance; while wild-type cells outcompete β-catenin-gain-of-function (βcatGOF) cells, Hras cells outcompete wild-type cells. Here we ask how metabolic states change as wild-type stem cells interface with mutant cells and drive different cell-competition outcomes.

SGLT2 inhibition alters substrate utilization and mitochondrial redox in healthy and failing rat hearts.

Previous studies highlight the potential for sodium-glucose cotransporter type 2 (SGLT2) inhibitors (SGLT2i) to exert cardioprotective effects in heart failure by increasing plasma ketones and shifting myocardial fuel utilization toward ketone oxidation. However, SGLT2i have multiple in vivo effects and the differential impact of SGLT2i treatment and ketone supplementation on cardiac metabolism remains unclear. Here, using gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-tandem mass spectrometry (LC-MS/MS) methodology combined with infusions of [13C6]glucose or [13C4]βOHB, we demonstrate that acute SGLT2 inhibition with dapagliflozin shifts relative rates of myocardial mitochondrial metabolism toward ketone oxidation, decreasing pyruvate oxidation with little effect on fatty acid oxidation in awake rats.

The effectiveness of homeopathy in relieving symptoms and reducing antibiotic use in patients with otitis media: A systematic review and meta-analysis.

Aim: This systematic review of clinical trial evidence aims to determine whether homeopathy can effectively relieve symptoms and reduce antibiotic use in patients diagnosed with otitis media (OM).

Methods: Seven databases and four trial registries were searched. Eligible studies included randomised- and non-randomised-controlled-trials in patients diagnosed with OM.

Success of medication abortion with mifepristone followed by two doses of misoprostol in very early pregnancy.

Objectives: To compare medication abortion (MAB) success in very early pregnancy (VEP) with mifepristone followed by either one or two doses of misoprostol.

Study Design: We performed a retrospective cohort analysis of VEP MABs from July 1, 2021 to May 31, 2022 treated with mifepristone 200 mg oral followed by a single dose of misoprostol 800 mcg buccal 24 to 48 hours later and MABs from June 21, 2022 to October 31, 2022 treated with mifepristone 200 mg oral followed by two doses of misoprostol 800 mcg buccal spaced 4 hours apart, with first dose taken 24 to 48 hours after mifepristone. Serum BhCG was collected at the time of mifepristone treatment with additional BhCG collected 48 to 72 hours after misoprostol treatment in both groups.

The mouse metabolic phenotyping center (MMPC) live consortium: an NIH resource for in vivo characterization of mouse models of diabetes and obesity.

The Mouse Metabolic Phenotyping Center (MMPC)Live Program was established in 2023 by the National Institute for Diabetes, Digestive and Kidney Diseases (NIDDK) at the National Institutes of Health (NIH) to advance biomedical research by providing the scientific community with standardized, high quality phenotyping services for mouse models of diabetes and obesity. Emerging as the next iteration of the MMPC Program which served the biomedical research community for 20 years (2001-2021), MMPCLive is designed as an outwardly-facing consortium of service cores that collaborate to provide reduced-cost consultation and metabolic, physiologic, and behavioral phenotyping tests on live mice for U.S.

A kidney-hypothalamus axis promotes compensatory glucose production in response to glycosuria.

The kidneys facilitate energy conservation through reabsorption of nutrients including glucose. Almost all the filtered blood glucose is reabsorbed by the kidneys. Loss of glucose in urine (glycosuria) is offset by an increase in endogenous glucose production to maintain normal energy supply in the body.

Heterogeneous gene expression during early arteriovenous fistula remodeling suggests that downregulation of metabolism predicts adaptive venous remodeling.

Clinical outcomes of arteriovenous fistulae (AVF) for hemodialysis remain inadequate since biological mechanisms of AVF maturation and failure are still poorly understood. Aortocaval fistula creation (AVF group) or a sham operation (sham group) was performed in C57BL/6 mice. Venous limbs were collected on postoperative day 7 and total RNA was extracted for high throughput RNA sequencing and bioinformatic analysis.

Development of Ac-doped biocompatible nanoparticles for targeted alpha therapy.

Targeted alpha therapy (TAT) relies on chemical affinity or active targeting using radioimmunoconjugates as strategies to deliver α-emitting radionuclides to cancerous tissue. These strategies can be affected by transmetalation of the parent radionuclide by competing ions in vivo and the bond-breaking recoil energy of decay daughters. The retention of α-emitting radionuclides and the dose delivered to cancer cells are influenced by these processes.

Deficits in brain glucose transport among younger adults with obesity.

Objective: Obesity is associated with alterations in eating behavior and neurocognitive function. In this study, we investigate the effect of obesity on brain energy utilization, including brain glucose transport and metabolism.

Methods: A total of 11 lean participants and 7 young healthy participants with obesity (mean age, 27 years) underwent magnetic resonance spectroscopy scanning coupled with a hyperglycemic clamp (target, ~180 mg/dL) using [1-C] glucose to measure brain glucose uptake and metabolism, as well as peripheral markers of insulin resistance.

Fatty acid binding protein 5 suppression attenuates obesity-induced hepatocellular carcinoma by promoting ferroptosis and intratumoral immune rewiring.

Due to the rise in overnutrition, the incidence of obesity-induced hepatocellular carcinoma (HCC) will continue to escalate; however, our understanding of the obesity to HCC developmental axis is limited. We constructed a single-cell atlas to interrogate the dynamic transcriptomic changes during hepatocarcinogenesis in mice. Here we identify fatty acid binding protein 5 (FABP5) as a driver of obesity-induced HCC.

Suspicious Ultrasound-Occult Non-Calcified Mammographic Masses, Asymmetries, and Architectural Distortions Are Moderate Probability for Malignancy.

Suspicious non-calcified mammographic findings have not been evaluated with modern mammographic technique, and the purpose of this work is to compare the likelihood of malignancy for those findings. To do this, 5018 consecutive mammographically guided biopsies performed during 2016-2019 at a large metropolitan, community-based hospital system were retrospectively reviewed. In total, 4396 were excluded for targeting calcifications, insufficient follow-up, or missing data.

Novel muscle-derived extracellular matrix hydrogel promotes angiogenesis and neurogenesis in volumetric muscle loss.

Volumetric muscle loss (VML) represents a clinical challenge due to the limited regenerative capacity of skeletal muscle. Most often, it results in scar tissue formation and loss of function, which cannot be prevented by current therapies. Decellularized extracellular matrix (DEM) has emerged as a native biomaterial for the enhancement of tissue repair.

Metabolic underpinnings of cancer-related fatigue.

Cancer-related fatigue (CRF) is one of the most prevalent and detrimental complications of cancer. Emerging evidence suggests that obesity and insulin resistance are associated with CRF occurrence and severity in cancer patients and survivors. In this narrative review, we analyzed recent studies including both preclinical and clinical research on the relationship between obesity and/or insulin resistance and CRF.

Thiazolidinedione enhances the efficacy of anti-PD-1 monoclonal antibody in murine melanoma.

Several clinical studies observed a surprising beneficial effect of obesity on enhancing immunotherapy responsiveness in patients with melanoma, highlighting an as-yet insufficiently understood relationship between metabolism and immunogenicity. Here, we demonstrate that the thiazolidinedione (TZD) rosiglitazone, a drug commonly used to treat diabetes by sequestering fatty acids in metabolically inert subcutaneous adipose tissue, improved sensitivity to anti-programmed cell death protein 1 (PD-1) treatment in YUMMER1.7 tumor-bearing mice, an initially immunotherapy-sensitive murine melanoma model.

Pharmacological and non-pharmacological interventions to prevent delirium after cardiac surgery: a protocol for a systematic review and meta-analysis.

Introduction: Delirium is a syndrome characterised by a disturbance in attention, awareness and cognition as a result of another physical condition. It occurs in up to 50% of patients after cardiac surgery and is associated with increased mortality, prolonged intensive care and hospital stay and long-term cognitive dysfunction. Identifying effective preventive interventions is important.

Molecular Mechanism of Fasting-Mimicking Diet in Inhibiting Colorectal Cancer Progression: Implications for Immune Therapy and Metabolic Regulation.

Recently, fasting-mimicking diet and caloric restriction have been shown to improve antitumor immunity. In this issue of Cancer Research, Zhong and colleagues provide insights into the molecular mechanism of fasting-mimicking diet-mediated metabolic reprogramming in colorectal cancer progression. The authors performed comprehensive mechanistic experiments in mouse models to show that fasting-mimicking diet prevents colorectal cancer progression by lowering intratumoral IgA+ B cells by accelerating fatty acid oxidation to inhibit B-cell IgA class switching.

A kidney-hypothalamus axis promotes compensatory glucose production in response to glycosuria.

The kidneys facilitate energy conservation through reabsorption of nutrients including glucose. Almost all the filtered blood glucose is reabsorbed by the kidneys. Loss of glucose in urine (glycosuria) is offset by an increase in endogenous glucose production to maintain normal energy supply in the body.

Dichloroacetate as a novel pharmaceutical treatment for cancer-related fatigue in melanoma.

Cancer-related fatigue (CRF) is one of the most common complications in patients with multiple cancer types and severely affects patients' quality of life. However, there have only been single symptom-relieving adjuvant therapies but no effective pharmaceutical treatment for the CRF syndrome. Dichloroacetate (DCA), a small molecule inhibitor of pyruvate dehydrogenase kinase, has been tested as a potential therapy to slow tumor growth, based largely on its effects in vitro to halt cell division.

The Role of the Mediterranean Diet in Breast Cancer Survivorship: A Systematic Review and Meta-Analysis of Observational Studies and Randomised Controlled Trials.

Female breast cancer is the most frequently diagnosed cancer. The long-term survival rates for this disease have increased; however, the unique demand for high-quality healthcare to improve breast-cancer survivorship are commonly unmet. The Mediterranean diet (MD) is associated with reduced breast-cancer risk and various health-related benefits in the general population, but its effect on breast-cancer survivors remains uncertain.

Tissue-specific reprogramming of glutamine metabolism maintains tolerance to sepsis.

Reprogramming metabolism is of great therapeutic interest for reducing morbidity and mortality during sepsis-induced critical illness. Disappointing results from randomized controlled trials targeting glutamine and antioxidant metabolism in patients with sepsis have begged a deeper understanding of the tissue-specific metabolic response to sepsis. The current study sought to fill this gap.