2024 Taiwan clinical practice guideline for diabetic kidney disease - an executive summary.

Scientific advances and development in the management of diabetes including use of new glucose-lowering agents for cardiorenal protection in diabetic patients prompted revision of local clinical practice guideline for diabetic kidney disease (DKD). Multiple cross-disciplinary professional meetings were held in 2023 and 2024 by experts from the Diabetes Association of the Republic of China (Taiwan), the Taiwanese Association of Diabetes Educators and the Taiwan Society of Nephrology to review the latest evidence and to develop updated recommendations, taking local epidemiology, circumstances and relevant local guidelines into considerations. From screening and diagnosis; risk classification and monitoring; lifestyle modifications; glycemic, blood pressure and lipid management; to the use of cardiorenal protective medications and complication management, the 2024 Taiwan Clinical Practice Guideline for DKD aims to offer up-to-date reference and comprehensive guidance to local practitioners for optimization of DKD patient care.

KLF5 Regulation of Exosome-Derived miR-152-3p From Bone Marrow Stem Cells Improves Ventricular Arrhythmia After Myocardial Infarction.

Cardiac fibroblasts (CFs) are activated into cardiac myofibroblasts (CMFs) in myocardial infarction (MI) and promote fibrosis, playing a crucial role in deteriorating cardiac function and inducing fatal arrhythmias. Transplantation of bone marrow mesenchymal stem cells (BMSCs) has emerged as a promising therapeutic approach for ischemic heart diseases, including MI. Recent studies have indicated that BMSCs can modulate the survival, differentiation, and antifibrotic activity of CFs.

Sphingosine simultaneously inhibits nuclear import and activates PP2A by binding importins and PPP2R1A.

Sphingosine and constrained analogs like FTY720 and SH-BC-893 restrain tumor growth through incompletely defined mechanisms that include protein phosphatase 2A (PP2A) activation. Here we show that these compounds directly bind not only the PP2A scaffolding subunit PPP2R1A, but also the structurally related karyopherins importin-β1 (KPNB1), transportin-1 (TNPO1), importin-5 (IPO5), and importin-7 (IPO7). Binding to sphingosine-like molecules triggers reversible unfolding of these target proteins, resulting in activation of PP2A and inhibition of importins.

Overlooked Trigger of Migraine: Clinical Significance of Small- and Medium-Shunt Patent Foramen Ovale.

Introduction: Patent foramen ovale (PFO) is a prevalent congenital heart malformation closely linked with migraine. The effect of PFO size on migraine remains controversial.

Methods: This study analyzed migraine patients who underwent PFO closure at our institution from January 2020 through December 2022.

Predicting catheter removal in peritoneal dialysis peritonitis patients visiting the emergency department: a multivariable logistic regression and decision tree analysis.

Peritonitis is a debilitating complication of peritoneal dialysis (PD). Identifying high-risk patients requiring PD catheter removal based on early information in the emergency room (ER) is critical. This cross-sectional study included 518 PD patients who visited the ER in the Chang Gung Memorial Hospital, Chia-Yi branch between 2002 and 2018.

Metabolic Objectives and Trade-Offs: Inference and Applications.

Determining appropriate cellular objectives is crucial for the system-scale modeling of biological networks for metabolic engineering, cellular reprogramming, and drug discovery applications. The mathematical representation of metabolic objectives can describe how cells manage limited resources to achieve biological goals within mechanistic and environmental constraints. While rapidly proliferating cells like tumors are often assumed to prioritize biomass production, mammalian cell types can exhibit objectives beyond growth, such as supporting tissue functions, developmental processes, and redox homeostasis.

Outcomes of K-Clip Implantation for Functional Tricuspid Regurgitation Accompanied with Persistent Atrial Fibrillation.

Atrial fibrillation (AF) has been identified as a risk factor for functional tricuspid regurgitation (FTR) in the absence of other known etiologies, although limited interventional options are available. K-Clip™, a novel transcatheter tricuspid annuloplasty device, is a clip-based annular plication approach for FTR. To date, no studies have investigated the short-term outcomes of K-Clip™ for patients with severe FTR associated with AF.

Nutrient control of splice site selection contributes to methionine addiction of cancer.

Objective: Many cancer cells depend on exogenous methionine for proliferation, whereas non-tumorigenic cells can divide in media supplemented with the metabolic precursor homocysteine. This phenomenon is known as methionine dependence of cancer or methionine addiction. The underlying mechanisms driving this cancer-specific metabolic addiction are poorly understood.

Inferring metabolic objectives and trade-offs in single cells during embryogenesis.

While proliferating cells optimize their metabolism to produce biomass, the metabolic objectives of cells that perform non-proliferative tasks are unclear. The opposing requirements for optimizing each objective result in a trade-off that forces single cells to prioritize their metabolic needs and optimally allocate limited resources. Here, we present single-cell optimization objective and trade-off inference (SCOOTI), which infers metabolic objectives and trade-offs in biological systems by integrating bulk and single-cell omics data, using metabolic modeling and machine learning.

Quercetin Alleviates Cardiac Fibrosis via Regulating the SIRT3 Signaling Pathway.

Purpose: Cardiovascular diseases, exacerbated by cardiac fibrosis, are the leading causes of mortality. We aimed to determine the role of quercetin (QU) in cardiac fibrosis and the underlying mechanism.

Methods: In this study, 8-week-old mice were subjected to either transverse aortic constriction (TAC) or sham surgery, then they were administered QU or saline.

Outcome of Transcatheter Aortic Valve Replacement for Pure Native Aortic Regurgitation in Patients with Pulmonary Hypertension.

Background: In recent years, transcatheter aortic valve replacement (TAVR) has emerged as a pivotal treatment for pure native aortic regurgitation (PNAR). Given patients with severe aortic regurgitation (AR) are prone to suffer from pulmonary hypertension (PH), understanding TAVR's efficacy in this context is crucial. This study aims to explore the short-term prognosis of TAVR in PNAR patients with concurrent PH.

Short-Term Outcomes of Transcatheter Aortic Valve Replacement in Low-Risk Patients With Pure Severe Aortic Regurgitation.

Transcatheter aortic valve replacement (TAVR) has emerged as an alternative treatment for patients with pure severe aortic regurgitation (PSAR) who are contraindicated for surgery or have a high surgical risk. However, the therapeutic efficacy and safety of TAVR in low Society of Thoracic Surgeons (STS) score risk patients remain to be clarified. This study aimed to explore the feasibility of TAVR treatment in different STS-risk patients and to compare the adverse events between the groups.

Targeting Macrophages: Therapeutic Approaches in Diabetic Kidney Disease.

Diabetes is not solely a metabolic disorder but also involves inflammatory processes. The immune response it incites is a primary contributor to damage in target organs. Research indicates that during the initial phases of diabetic nephropathy, macrophages infiltrate the kidneys alongside lymphocytes, initiating a cascade of inflammatory reactions.

Discovery of compounds that reactivate p53 mutants in vitro and in vivo.

The tumor suppressor p53 is the most frequently mutated protein in human cancer. The majority of these mutations are missense mutations in the DNA binding domain of p53. Restoring p53 tumor suppressor function could have a major impact on the therapy for a wide range of cancers.

New Insights into the Treatment of Glomerular Diseases: When Mechanisms Become Vivid.

Treatment for glomerular diseases has been extrapolated from the experience of other autoimmune disorders while the underlying pathogenic mechanisms were still not well understood. As the classification of glomerular diseases was based on patterns of juries instead of mechanisms, treatments were typically the art of try and error. With the advancement of molecular biology, the role of the immune agent in glomerular diseases is becoming more evident.

Relationship Between Serum Concentration of Adrenomedullin and Myocardial Ischemic T Wave Changes in Patients With Lung Cancer.

Background: Patients with lung cancer are at increased risk for the development of cardiovascular diseases. Molecular markers for early diagnosis of cardiac ischemia are of great significance for the early prevention of cardiovascular events in patients with lung cancer. By evaluating the relationship between adrenomedullin (ADM) and myocardial ischemic T wave changes, the clinical value of circulating ADM as a predictor of myocardial ischemia in patients with lung cancer is confirmed.

Metabolic remodelling during early mouse embryo development.

During early mammalian embryogenesis, changes in cell growth and proliferation depend on strict genetic and metabolic instructions. However, our understanding of metabolic reprogramming and its influence on epigenetic regulation in early embryo development remains elusive. Here we show a comprehensive metabolomics profiling of key stages in mouse early development and the two-cell and blastocyst embryos, and we reconstructed the metabolic landscape through the transition from totipotency to pluripotency.

Next-Generation Genome-Scale Metabolic Modeling through Integration of Regulatory Mechanisms.

Genome-scale metabolic models (GEMs) are powerful tools for understanding metabolism from a systems-level perspective. However, GEMs in their most basic form fail to account for cellular regulation. A diverse set of mechanisms regulate cellular metabolism, enabling organisms to respond to a wide range of conditions.

Localized Proteolysis for the Construction of Intracellular Asymmetry in .

Protein-level regulations have gained importance in building synthetic circuits, as they offer a potential advantage in the speed of operation compared to gene regulation circuits. In nature, localized protein degradation is prevalent in polarizing cellular signaling. We, therefore, set out to systematically investigate whether localized proteolysis can be employed to construct intracellular asymmetry in .

Association of furosemide or hydrochlorothiazide use with risk of atrial fibrillation post pacemaker implantation among elderly patients.

Background: Atrial fibrillation (AF) induced by artificial pacing is directly related to atrial remodeling. Previous basic research has shown that furosemide aggravates pathologic myocardial remodeling while hydrochlorothiazide alleviates it. However, whether furosemide or hydrochlorothiazide plays a role in developing AF after pacemaker implantation remains unknown.

Lipid remodeling in response to methionine stress in MDA-MBA-468 triple-negative breast cancer cells.

Methionine (Met) is an essential amino acid and critical precursor to the cellular methyl donor S-adenosylmethionine. Unlike nontransformed cells, cancer cells have a unique metabolic requirement for Met and are unable to proliferate in growth media where Met is replaced with its metabolic precursor, homocysteine. This metabolic vulnerability is common among cancer cells regardless of tissue origin and is known as "methionine dependence", "methionine stress sensitivity", or the Hoffman effect.

Construction of intracellular asymmetry and asymmetric division in Escherichia coli.

The design principle of establishing an intracellular protein gradient for asymmetric cell division is a long-standing fundamental question. While the major molecular players and their interactions have been elucidated via genetic approaches, the diversity and redundancy of natural systems complicate the extraction of critical underlying features. Here, we take a synthetic cell biology approach to construct intracellular asymmetry and asymmetric division in Escherichia coli, in which division is normally symmetric.

A New Monitoring Effort for Asia: The Asia Pacific Mercury Monitoring Network (APMMN).

The Asia Pacific Mercury Monitoring Network (APMMN) cooperatively measures mercury in precipitation in a network of sites operating in Asia and the Western Pacific region. The network addresses significant data gaps in a region where mercury emission estimates are the highest globally, and available measurement data are limited. The reduction of mercury emissions under the Minamata Convention on Mercury also justifies the need for continent-wide and consistent observations that can help determine the magnitude of the problem and assess the efficacy of reductions over time.

Eight-year dry deposition of atmospheric mercury to a tropical high mountain background site downwind of the East Asian continent.

Atmospheric deposition, either dry or wet, has been identified as an important pathway of mercury (Hg) input to terrestrial and aquatic systems. Although East Asia is the major atmospheric Hg emission source region, very few studies have been conducted to quantify atmospheric Hg deposition in its downwind region. In this study, 8-year (2009-2016) atmospheric Hg dry deposition was reported at the Lulin Atmospheric Background Station (LABS), a high mountain forest site in central Taiwan.