The role of IL-1 family cytokines in diabetic cardiomyopathy.

Diabetic cardiomyopathy (DCM) is the primary cause of heart failure in patients with diabetes and is characterised by contractile dysfunction and left ventricular hypertrophy. The complex pathological and physiological mechanisms underlying DCM have contributed to a limited number of available treatment options. A substantial body of evidence has established that DCM is a low-grade inflammatory cardiovascular disorder, with the interleukin-1 (IL-1) family of cytokines playing crucial roles in initiating inflammatory responses and shaping innate and adaptive immunity.

The effect of different dietary restriction on weight management and metabolic parameters in people with type 2 diabetes mellitus: a network meta-analysis of randomized controlled trials.

Background: Type 2 diabetes mellitus (T2DM) is a globally prevalent chronic condition. Individuals with T2DM are at increased risk of developing complications associated with both macrovascular and microvascular pathologies. These comorbidities reduce patient quality of life and increase mortality.

Targeting cell death in NAFLD: mechanisms and targeted therapies.

Nonalcoholic fatty liver disease (NAFLD) is a group of chronic liver disease which ranges from simple steatosis (NAFL) to non-alcoholic steatohepatitis (NASH) and is characterized by lipid accumulation, inflammation activation, fibrosis, and cell death. To date, a number of preclinical studies or clinical trials associated with therapies targeting fatty acid metabolism, inflammatory factors and liver fibrosis are performed to develop effective drugs for NAFLD/NASH. However, few therapies are cell death signaling-targeted even though the various cell death modes are present throughout the progression of NAFLD/NASH.

Annexin A1 binds PDZ and LIM domain 7 to inhibit adipogenesis and prevent obesity.

Obesity is a global issue that warrants the identification of more effective therapeutic targets and a better understanding of the pivotal molecular pathogenesis. Annexin A1 (ANXA1) is known to inhibit phospholipase A2, exhibiting anti-inflammatory activity. However, the specific effects of ANXA1 in obesity and the underlying mechanisms of action remain unclear.

Fecal virome transplantation: A promising strategy for the treatment of metabolic diseases.

Metabolic diseases are a group of disorders caused by metabolic abnormalities, including obesity, diabetes, non-alcoholic fatty liver disease, and more. Increasing research indicates that, beyond inherent metabolic irregularities, the onset and progression of metabolic diseases are closely linked to alterations in the gut microbiota, particularly gut bacteria. Additionally, fecal microbiota transplantation (FMT) has demonstrated effectiveness in clinically treating metabolic diseases, notably diabetes.

The Role of Immune Cells in DKD: Mechanisms and Targeted Therapies.

Diabetic kidney disease (DKD), is a common microvascular complication and a major cause of death in patients with diabetes. Disorders of immune cells and immune cytokines can accelerate DKD development of in a number of ways. As the kidney is composed of complex and highly differentiated cells, the interactions among different cell types and immune cells play important regulatory roles in disease development.

BDH1-mediated βOHB metabolism ameliorates diabetic kidney disease by activation of NRF2-mediated antioxidative pathway.

A ketogenic diet (KD) and β-hydroxybutyrate (βOHB) have been widely reported as effective therapies for metabolic diseases. β-Hydroxybutyrate dehydrogenase 1 (BDH1) is the rate-limiting enzyme in ketone metabolism. In this study, we examined the BDH1-mediated βOHB metabolic pathway in the pathogenesis of diabetic kidney disease (DKD).

Based on network pharmacology and molecular docking to explore the molecular mechanism of Ginseng and Astragalus decoction against postmenopausal osteoporosis.

Traditional Chinese medicine suggests that Ginseng and Astragalus Decoction (GAD) may effectively treat postmenopausal osteoporosis (PMO). However, the exact mechanism of action for GAD remains unclear. This study aims to utilize network pharmacology and molecular docking technology to explore the potential mechanism of GAD in treating PMO.

Bdh1 overexpression ameliorates hepatic injury by activation of Nrf2 in a MAFLD mouse model.

In 2020, a group of experts officially suggested metabolic dysfunction associated with fatty liver disease "MAFLD" as a more appropriate overarching term than NAFLD, indicating the key role of metabolism in fatty liver disease. Bdh1, as the rate-limiting enzyme of ketone metabolism, acts as an important metabolic regulator in liver. However, the role of Bdh1 in MAFLD is unclear.

Chronic Ethanol Consumption Induces Osteopenia via Activation of Osteoblast Necroptosis.

Chronic high-dose alcohol consumption impairs bone remodeling, reduces bone mass, and increases the risk of osteoporosis and bone fracture. However, the mechanisms underlying alcohol-induced osteoporosis are yet to be elucidated. In this study, we showed that excess intake of ethyl alcohol (EtOH) resulted in osteopenia and osteoblast necroptosis in mice that led to necrotic lesions and reduced osteogenic differentiation in bone marrow mesenchymal stem cells (BMMSCs).

G-quadruplex DNA: a novel target for drug design.

G-quadruplex (G4) DNA is a type of quadruple helix structure formed by a continuous guanine-rich DNA sequence. Emerging evidence in recent years authenticated that G4 DNA structures exist both in cell-free and cellular systems, and function in different diseases, especially in various cancers, aging, neurological diseases, and have been considered novel promising targets for drug design. In this review, we summarize the detection method and the structure of G4, highlighting some non-canonical G4 DNA structures, such as G4 with a bulge, a vacancy, or a hairpin.

A Toolbox for Site-Specific Labeling of RecQ Helicase With a Single Fluorophore Used in the Single-Molecule Assay.

Fluorescently labeled proteins can improve the detection sensitivity and have been widely used in a variety of biological measurements. In single-molecule assays, site-specific labeling of proteins enables the visualization of molecular interactions, conformational changes in proteins, and enzymatic activity. In this study, based on a flexible linker in the RecQ helicase, we established a scheme involving a combination of fluorophore labeling and sortase A ligation to allow site-specific labeling of the HRDC domain of RecQ with a single Cy5 fluorophore, without inletting extra fluorescent domain or peptide fragment.

Protein Phosphatase 6 Protects Prophase I-Arrested Oocytes by Safeguarding Genomic Integrity.

Mammalian oocytes are arrested at prophase of the first meiotic division in the primordial follicle pool for months, even years, after birth depending on species, and only a limited number of oocytes resume meiosis, complete maturation, and ovulate with each reproductive cycle. We recently reported that protein phosphatase 6 (PP6), a member of the PP2A-like subfamily, which accounts for cellular serine/threonine phosphatase activity, functions in completing the second meiosis. Here, we generated mutant mice with a specific deletion of Ppp6c in oocytes from the primordial follicle stage by crossing Ppp6cF/F mice with Gdf9-Cre mice and found that Ppp6cF/F; GCre+ mice are infertile.

Oocyte-specific deletion of N-WASP does not affect oocyte polarity, but causes failure of meiosis II completion.

Study Question: There is an unexplored physiological role of N-WASP (neural Wiskott-Aldrich syndrome protein) in oocyte maturation that prevents completion of second meiosis.

Summary Answer: In mice, N-WASP deletion did not affect oocyte polarity and asymmetric meiotic division in first meiosis, but did impair midbody formation and second meiosis completion.

What Is Known Already: N-WASP regulates actin dynamics and participates in various cell activities through the RHO-GTPase-Arp2/3 (actin-related protein 2/3 complex) pathway, and specifically the Cdc42 (cell division cycle 42)-N-WASP-Arp2/3 pathway.

Geminin deletion in mouse oocytes results in impaired embryo development and reduced fertility.

Geminin controls proper centrosome duplication, cell division, and differentiation. We investigated the function of geminin in oogenesis, fertilization, and early embryo development by deleting the geminin gene in oocytes from the primordial follicle stage. Oocyte-specific disruption of geminin results in low fertility in mice.

LKB1 acts as a critical gatekeeper of ovarian primordial follicle pool.

Liver Kinase b1 (LKB1/STK11)is a tumor suppressor responsible for the Peutz-Jeghers syndrome, an autosomal-dominant, cancer-prone disorder in which patients develop neoplasms in several organs, including the oviduct, ovary, and cervix. Besides, the C allele of a SNP in the Lkb1 gene impedes the likelihood of ovulation in polycystic ovary syndrome (PCOS) in women treated with metformin, a known LKB1-AMPK activator. It is very likely that LKB1 plays roles in female fertility.

Loss of protein phosphatase 6 in oocytes causes failure of meiosis II exit and impaired female fertility.

Dynamic protein phosphorylation and dephosphorylation, mediated by a conserved cohort of protein kinases and phosphatases, regulate cell cycle progression. Among the well-known PP2A-like protein phosphatases, protein phosphatase 6 (PP6) has been analyzed in mammalian mitosis, and Aurora A has recently been identified as its key substrate. However, the functions of PP6 in meiosis are still entirely unknown.

Scaffold subunit Aalpha of PP2A is essential for female meiosis and fertility in mice.

Ppp2r1a encodes the scaffold subunit Aalpha of protein phosphatase 2A (PP2A), which is an important and ubiquitously expressed serine threonine phosphatase family and plays a critical role in many fundamental cellular processes. To identify the physiological role of PP2A in female germ cell meiosis, we selectively disrupted Ppp2r1a expression in oocytes by using the Cre-Loxp conditional knockout system. Here we report for the first time that oocyte-specific deletion of Ppp2r1a led to severe female subfertility without affecting follicle survival, growth, and ovulation.

Specific deletion of Cdc42 does not affect meiotic spindle organization/migration and homologous chromosome segregation but disrupts polarity establishment and cytokinesis in mouse oocytes.

Mammalian oocyte maturation is distinguished by highly asymmetric meiotic divisions during which a haploid female gamete is produced and almost all the cytoplasm is maintained in the egg for embryo development. Actin-dependent meiosis I spindle positioning to the cortex induces the formation of a polarized actin cap and oocyte polarity, and it determines asymmetric divisions resulting in two polar bodies. Here we investigate the functions of Cdc42 in oocyte meiotic maturation by oocyte-specific deletion of Cdc42 through Cre-loxP conditional knockout technology.