Gut microbiome and metabolites mediate the benefits of caloric restriction in mice after acute kidney injury.

The role of gut microbiome in acute kidney injury (AKI) is increasing recognized. Caloric restriction (CR) has been shown to enhance the resistance to ischemia/reperfusion injury to the kidneys in rodents. Nonetheless, it is unknown whether intestinal microbiota mediated CR protection against ischemic/reperfusion-induced injury (IRI) in the kidneys.

Pharmacology of Hydrogen Sulfide and Its Donors in Cardiometabolic Diseases.

Cardiometabolic diseases (CMDs) are major contributors to global mortality, emphasizing the critical need for novel therapeutic interventions. Hydrogen sulfide (HS) has garnered enormous attention as a significant gasotransmitter with various physiological, pathophysiological, and pharmacological impacts within mammalian cardiometabolic systems. In addition to its roles in attenuating oxidative stress and inflammatory response, burgeoning research emphasizes the significance of HS in regulating proteins via persulfidation, a well known modification intricately associated with the pathogenesis of CMDs.

Vaccarin alleviates septic cardiomyopathy by potentiating NLRP3 palmitoylation and inactivation.

Background: Sepsis often leads to significant morbidity and mortality due to severe myocardial injury. As is known, the activation of NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome crucially contributes to septic cardiomyopathy (SCM) by facilitating the secretion of interleukin (IL)-1β and IL-18. The removal of palmitoyl groups from NLRP3 is a crucial step in the activation of the NLRP3 inflammasome.

Cichoric acid ameliorates sepsis-induced acute kidney injury by inhibiting M1 macrophage polarization.

Cichoric acid (CA), a widely utilized polyphenolic compound in medicine, has garnered significant attention due to its potential health benefits. Sepsis-induced acute kidney disease (AKI) is related with an elevated risk of end-stage kidney disease (ESKD). However, it remains unclear whether CA provides protection against septic AKI.

Deficiency of neutral cholesterol ester hydrolase 1 (NCEH1) impairs endothelial function in diet-induced diabetic mice.

Background: Neutral cholesterol ester hydrolase 1 (NCEH1) plays a critical role in the regulation of cholesterol ester metabolism. Deficiency of NCHE1 accelerated atherosclerotic lesion formation in mice. Nonetheless, the role of NCEH1 in endothelial dysfunction associated with diabetes has not been explored.

Spatial Gene-Expression Profiling Unveils Immuno-oncogenic Programs of NF1-Associated Peripheral Nerve Sheath Tumor Progression.

Purpose: Plexiform neurofibromas (PNF) are benign peripheral nerve sheath tumors (PNST) associated with neurofibromatosis type 1 (NF1). Despite similar histologic appearance, these neoplasms exhibit diverse evolutionary trajectories, with a subset progressing to malignant peripheral nerve sheath tumor (MPNST), the leading cause of premature death in individuals with NF1. Malignant transformation of PNF often occurs through the development of atypical neurofibroma (ANF) precursor lesions characterized by distinct histopathologic features and CDKN2A copy-number loss.

Disrupted cardiac fibroblast BCAA catabolism contributes to diabetic cardiomyopathy via a periostin/NAP1L2/SIRT3 axis.

Background: Periostin is an extracellular matrix protein that plays a critical role in cell fate determination and tissue remodeling, but the underlying role and mechanism of periostin in diabetic cardiomyopathy (DCM) are far from clear. Thus, we aimed to clarify the mechanistic participation of periostin in DCM.

Methods: The expression of periostin was examined in DCM patients, diabetic mice and high glucose (HG)-exposed cardiac fibroblasts (CF).

Chicoric acid ameliorates sepsis-induced cardiomyopathy via regulating macrophage metabolism reprogramming.

Background: Sepsis-related cardiac dysfunction is believed to be a primary cause of high morbidity and mortality. Metabolic reprogramming is closely linked to NLRP3 inflammasome activation and dysregulated glycolysis in activated macrophages, leading to inflammatory responses in septic cardiomyopathy. Succinate dehydrogenase (SDH) and succinate play critical roles in the progression of metabolic reprogramming in macrophages.

Impact of lipid profiles on parenchymal hemorrhage and early outcome after mechanical thrombectomy.

Objective: We aimed to investigate the association of lipid parameters with parenchymal hemorrhage (PH) and early neurological improvement (ENI) after mechanical thrombectomy (MT) in stroke patients.

Methods: We retrospectively analyzed consecutive patients who underwent MT between January 2019 and February 2022 at a tertiary stroke center. PH was diagnosed and classified as PH-1 and PH-2 according to the European Cooperative Acute Stroke Study definition.

Combined CDK4/6 and ERK1/2 Inhibition Enhances Antitumor Activity in NF1-Associated Plexiform Neurofibroma.

Purpose: Plexiform neurofibromas (PNF) are peripheral nerve sheath tumors that cause significant morbidity in persons with neurofibromatosis type 1 (NF1), yet treatment options remain limited. To identify novel therapeutic targets for PNF, we applied an integrated multi-omic approach to quantitatively profile kinome enrichment in a mouse model that has predicted therapeutic responses in clinical trials for NF1-associated PNF with high fidelity.

Experimental Design: Utilizing RNA sequencing combined with chemical proteomic profiling of the functionally enriched kinome using multiplexed inhibitor beads coupled with mass spectrometry, we identified molecular signatures predictive of response to CDK4/6 and RAS/MAPK pathway inhibition in PNF.

A Comprehensive Overview of the Role of Visual Cortex Malfunction in Depressive Disorders: Opportunities and Challenges.

Major depressive disorder (MDD) is a highly heterogeneous mental disorder, and its complex etiology and unclear mechanism are great obstacles to the diagnosis and treatment of the disease. Studies have shown that abnormal functions of the visual cortex have been reported in MDD patients, and the actions of several antidepressants coincide with improvements in the structure and synaptic functions of the visual cortex. In this review, we critically evaluate current evidence showing the involvement of the malfunctioning visual cortex in the pathophysiology and therapeutic process of depression.

Transcription factor cellular promoter 2 is required for upstream binding protein 1 -mediated angiogenesis.

Objective: Angiogenesis is a key process of repairing tissue damage, and it is regulated by the delicate balance between anti-angiogenesis factors. In the present study, we investigate whether transcription factor cellular promoter 2 (TFCP2) is required for upstream binding protein 1 (UBP1)-mediated angiogenesis.

Methods: Levels of UBP1 and TFCP2 in human umbilical vein endothelial cells (HUVECs) are detected by quantitative polymerase chain reaction (q-PCR) and Western blotting (WB).

Hydrogen sulfide in health and diseases: cross talk with noncoding RNAs.

Hydrogen sulfide (HS) is previously described as a potentially lethal toxic gas. However, this gasotransmitter is also endogenously generated by the actions of cystathionine-β-synthase (CBS), cystathionine-γ-lyase (CSE), and 3-mercaptopyruvate sulfurtransferase (3-MST) in mammalian systems, thus belonging to the family of gasotransmitters after nitric oxide (NO) and carbon monoxide (CO). The physiological or pathological significance of HS has been extensively expanded for decades.

Near-Infrared-Induced Photothermal Enhanced Photocatalytic H Production for 3D/2D Heterojunctions of Snowflake-like CuS/g-CN Nanosheets.

The conversion of solar power to hydrogen (H) energy efficiently encounters some obstacles due to the lack of superior catalysts and efficient catalytic approaches. Herein, three-dimensional/two-dimensional (3D/2D) CuS/g-CN photothermal catalysts were obtained via an easy, one-step hydrothermal method after pyrolysis. The favorable heterojunction interface for H production was constructed by snowflake-like CuS embedded in the graphite carbon nitride (g-CN) nanosheets, leading to the acceleration of charge transfer and separation, decrease of charge transfer distance, and perfect realization of photothermal effects (PTEs) induced by near-infrared (NIR) light.

Restoring mitochondrial cardiolipin homeostasis reduces cell death and promotes recovery after spinal cord injury.

Alterations in phospholipids have long been associated with spinal cord injury (SCI). However, their specific roles and signaling cascades in mediating cell death and tissue repair remain unclear. Here we investigated whether alterations of cardiolipin (CL), a family of mitochondrion-specific phospholipids, play a crucial role in mitochondrial dysfunction and neuronal death following SCI.

Benefits of Curcumin in the Vasculature: A Therapeutic Candidate for Vascular Remodeling in Arterial Hypertension and Pulmonary Arterial Hypertension?

Growing evidence suggests that hypertension is one of the leading causes of cardiovascular morbidity and mortality since uncontrolled high blood pressure increases the risk of myocardial infarction, aortic dissection, hemorrhagic stroke, and chronic kidney disease. Impaired vascular homeostasis plays a critical role in the development of hypertension-induced vascular remodeling. Abnormal behaviors of vascular cells are not only a pathological hallmark of hypertensive vascular remodeling, but also an important pathological basis for maintaining reduced vascular compliance in hypertension.

Selective activation of ABCA1/ApoA1 signaling in the V1 by magnetoelectric stimulation ameliorates depression via regulation of synaptic plasticity.

Emerging evidence suggests that dysfunction of the visual cortex may be involved in major depressive disorder (MDD). However, the underlying mechanisms remain unclear. We previously established that combined magnetic stimulation system treatment (c-MSST) resulted in an antidepressant effect in mice.

MiR-103a-3p aggravates renal cell carcinoma by targeting TMEM33.

Objective: We investigated the mechanism of miR-103a-3p-mediated renal cell carcinoma (RCC) progression.

Methods: The miR-103a-3p expressions were measured in clinical samples and in two RCC cell lines. MiR-103a-3p was inhibited or over-expressed in the 786-O and UO31 cell lines, respectively.

Brigatinib causes tumor shrinkage in both NF2-deficient meningioma and schwannoma through inhibition of multiple tyrosine kinases but not ALK.

Neurofibromatosis Type 2 (NF2) is an autosomal dominant genetic syndrome caused by mutations in the NF2 tumor suppressor gene resulting in multiple schwannomas and meningiomas. There are no FDA approved therapies for these tumors and their relentless progression results in high rates of morbidity and mortality. Through a combination of high throughput screens, preclinical in vivo modeling, and evaluation of the kinome en masse, we identified actionable drug targets and efficacious experimental therapeutics for the treatment of NF2 related schwannomas and meningiomas.