Research progress of cPLA2 in cardiovascular diseases (Review).

Cytoplasmic phospholipase A2 (cPLA2) is a vital member of the PLA2 family. Studies have demonstrated that cPLA2 plays a key role in various inflammatory‑related diseases and cancers. However, limited research has focused on cPLA2 in cardiovascular diseases.

Tau is a receptor with low affinity for glucocorticoids and is required for glucocorticoid-induced bone loss.

Glucocorticoids (GCs) are the most prescribed anti-inflammatory and immunosuppressive drugs. However, their use is often limited by substantial side effects, such as GC-induced osteoporosis (GIO) with the underlying mechanisms still not fully understood. In this study, we identify Tau as a low-affinity binding receptor for GCs that plays a crucial role in GIO.

Ellagic acid promotes osteoblasts differentiation via activating SMAD2/3 pathway and alleviates bone mass loss in OVX mice.

Characterized by bone mass loss, osteoporosis is an orthopedic disease typically found in postmenopausal women and aging individuals. Consistent with its pathogenesis summarized as an imbalance in bone formation/resorption, current pharmacologically therapeutic strategies for osteoporosis mainly aim to promote bone formation or/and inhibit bone resorption. However, few effective drugs with mild clinical side effects have been developed, making it a well-concerned issue to seek appropriate drugs for osteoporosis.

Vital role of SHMT2 in diverse disease.

One-carbon metabolism is essential for our human cells to carry out nucleotide synthesis, methylation, and reductive metabolism through one-carbon units, and these pathways ensure the high proliferation rate of cancer cells. Serine hydroxymethyltransferase 2 (SHMT2) is a key enzyme in one-carbon metabolism. This enzyme can convert serine into a one-carbon unit bound to tetrahydrofolate and glycine, ultimately supporting the synthesis of thymidine and purines and promoting the growth of cancer cells.

Phase Transformation and Performance of Mg-Based Hydrogen Storage Material by Adding ZnO Nanoparticles.

ZnO nanoparticles in a spherical-like structure were synthesized via filtration and calcination methods, and different amounts of ZnO nanoparticles were added to MgH via ball milling. The SEM images revealed that the size of the composites was about 2 μm. The composites of different states were composed of large particles with small particles covering them.

Periplocin targets low density lipoprotein receptor-related protein 4 to attenuate osteoclastogenesis and protect against osteoporosis.

Osteoporosis is a common inflammaging-related condition, where long-term accumulation of pro-inflammatory cytokines causes massive bone loss. Periplocin, a cardiotonic steroid isolated from Periploca forrestii, has been proved to reduce inflammation in several inflammatory diseases, such as rheumatoid arthritis. However, its effect and mechanism of inflammation in osteoporosis, in which pro-inflammatory factors accelerate bone loss, has not been well demonstrated.

Higenamine Promotes Osteogenesis Via IQGAP1/SMAD4 Signaling Pathway and Prevents Age- and Estrogen-Dependent Bone Loss in Mice.

Osteoporosis is a common bone disease caused by an imbalance of bone resorption and formation that results in a loss of total bone density. SMAD2/3 signal transduction is known to play a crucial role in osteogenic differentiation through transforming growth factor-beta (TGF-β). By screening a library of small-molecule compounds, the current study identifies higenamine (HG) as an active osteogenic agent that could be a therapeutic candidate for osteoporosis.

DEPDC1 as a crucial factor in the progression of human osteosarcoma.

Objective: Novel therapeutic strategies are emerging with the increased understanding of the underlying mechanisms of human osteosarcoma. This current study tends to decipher the potentially critical role of DEP domain-containing 1 (DEPDC1), a tumor-related gene, during the progression of osteosarcoma.

Methods: Bioinformatics analysis of 25,035 genes from the National Center for Biotechnology Information (NCBI) databases was performed to screen differentially expressed genes between osteosarcoma and normal control groups, complemented by the examination of 85 clinical osteosarcoma specimens.

Penfluridol targets acid sphingomyelinase to inhibit TNF signaling and is therapeutic against inflammatory autoimmune diseases.

Background: Penfluridol, isolated from an FDA-approved small-molecule drug library as an inhibitor of tumor necrosis factor α (TNFα)-stimulated NF-κB activation, is clinically used to treat chronic schizophrenia and related disorders. This study is aimed to investigate the therapeutic effect of penfluridol on TNFα-stimulated inflammatory autoimmune diseases, particularly inflammatory arthritis.

Methods: Various in vitro studies to confirm the inhibitory effect of penfluridol on TNFα-induced NF-κB activity in bone marrow-derived macrophages or Raw 264.

CircPrkcsh, a circular RNA, contributes to the polarization of microglia towards the M1 phenotype induced by spinal cord injury and acts via the JNK/p38 MAPK pathway.

Spinal cord injury (SCI) is a complex pathological change that includes primary SCI and gradually evolves into secondary SCI. Accumulating evidence demonstrates that circular RNAs (circRNAs) are involved in the pathology of a variety of neurological diseases and injuries. However, the characteristics and function of circRNAs in SCI have yet to be elucidated.

Cytosolic Phospholipase A2 Is Required for Fexofenadine's Therapeutic Effects against Inflammatory Bowel Disease in Mice.

Inflammatory Bowel Disease (IBD) is an autoimmune condition with complicated pathology and diverse clinical signs. TNFα is believed to play a crucial role in the pathogenesis of IBD. We recently identified fexofenadine, a well-known antagonist of histamine H1 receptor, as a novel inhibitor of TNFα signaling.

Fexofenadine Protects Against Intervertebral Disc Degeneration Through TNF Signaling.

Fexofenadine (FFD) is an antihistamine drug with an anti-inflammatory effect. The intervertebral disc (IVD) degeneration process is involved in inflammation in which tumor necrosis factor-α (TNF-α) plays an important role. This study aims to investigate the role of FFD in the pathological process of IVD degeneration.

14-3-3 epsilon is an intracellular component of TNFR2 receptor complex and its activation protects against osteoarthritis.

Objectives: Osteoarthritis (OA) is the most common joint disease; however, the indeterminate nature of mechanisms by which OA develops has restrained advancement of therapeutic targets. TNF signalling has been implicated in the pathogenesis of OA. TNFR1 primarily mediates inflammation, whereas emerging evidences demonstrate that TNFR2 plays an anti-inflammatory and protective role in several diseases and conditions.

Asenapine maleate inhibits angiotensin II-induced proliferation and activation of cardiac fibroblasts via the ROS/TGFβ1/MAPK signaling pathway.

Background: Cardiac fibrosis will increase wall stiffness and diastolic dysfunction, which will eventually lead to heart failure. Asenapine maleate (AM) is widely used in the treatment of schizophrenia. In the current study, we explored the potential mechanism underlying the role of AM in angiotensin II (Ang II)-induced cardiac fibrosis.

Reactive Astrogliosis: Implications in Spinal Cord Injury Progression and Therapy.

Astrocytes are the most populous glial cells in the central nervous system (CNS). They are essential to CNS physiology and play important roles in the maintenance of homeostasis, development of synaptic plasticity, and neuroprotection. Nevertheless, under the influence of certain factors, astrocytes may also exert detrimental effects through a process of reactive astrogliosis.

Progranulin deficiency exacerbates spinal cord injury by promoting neuroinflammation and cell apoptosis in mice.

Purpose: Spinal cord injury (SCI) often results in significant and catastrophic dysfunction and disability and imposes a huge economic burden on society. This study aimed to determine whether progranulin (PGRN) plays a role in the progressive damage following SCI and evaluate the potential for development of a PGRN derivative as a new therapeutic target in SCI.

Methods: PGRN-deficient (Gr) and wild-type (WT) littermate mice were subjected to SCI using a weight-drop technique.

Progranulin promotes diabetic fracture healing in mice with type 1 diabetes.

Type 1 diabetes mellitus (T1DM) is an autoimmune disease characterized by insulin deficiency, and patients with diabetes have an increased risk of bone fracture and significantly impaired fracture healing. Proinflammatory cytokine tumor necrosis factor-alpha is significantly upregulated in diabetic fractures and is believed to underlie delayed fracture healing commonly observed in diabetes. Our previous genetic screen for the binding partners of progranulin (PGRN), a growth factor-like molecule that induces chondrogenesis, led to the identification of tumor necrosis factor receptors (TNFRs) as the PGRN-binding receptors.

Downregulation of can enhance the radiosensitivity of osteosarcoma and .

To investigate the effect of gene on radiotherapy for osteosarcoma. Gene Expression Omnibus database, RT-qPCR and immunohistochemical analysis were performed. Cell proliferation and cell cycle experiments were conducted after knockdown of .

Fexofenadine inhibits TNF signaling through targeting to cytosolic phospholipase A2 and is therapeutic against inflammatory arthritis.

Objective: Tumour necrosis factor alpha (TNF-α) signalling plays a central role in the pathogenesis of various autoimmune diseases, particularly inflammatory arthritis. This study aimed to repurpose clinically approved drugs as potential inhibitors of TNF-α signalling in treatment of inflammatory arthritis.

Methods: In vitro and in vivo screening of an Food and Drug Administration (FDA)-approved drug library; in vitro and in vivo assays for examining the blockade of TNF actions by fexofenadine: assays for defining the anti-inflammatory activity of fexofenadine using TNF-α transgenic (TNF-tg) mice and collagen-induced arthritis in DBA/1 mice.

Silencing miR-21 induces polarization of astrocytes to the A2 phenotype and improves the formation of synapses by targeting glypican 6 the signal transducer and activator of transcription-3 pathway after acute ischemic spinal cord injury.

Ischemic spinal cord injury (ISCI) results in the motor sensory dysfunction of the limbs below the injury site. In response to the injury, astrocytes develop into neuroprotective astrocytes [(neurotrophic reactive astrocytes (A2s)] to mitigate the damage. MicroRNA (miR)-21 can promote the development of neuroinflammation in previous studies.

Clinical Application of Teriparatide in Fracture Prevention: A Systematic Review.

Background: Teriparatide, a 1-34 fragment of parathyroid hormone (PTH) that maintains most of the biological activities of PTH, has been employed since 2002 as an anabolic agent for osteoporotic individuals who are at high risk of fracture. The purpose of the present review is to provide a systematic summary and timely update on treatment with teriparatide for fracture prevention.

Methods: Electronic databases, including OVID MEDLINE, OVID Embase, and the Cochrane Library, were searched on February 9, 2018, to identify published systematic reviews and meta-analyses addressing treatment with teriparatide for fracture prevention, and A Measurement Tool to Assess Systematic Reviews 2 (AMSTAR 2) was used to assess the quality of included studies.

microRNA-21 regulates astrocytic reaction post-acute phase of spinal cord injury through modulating TGF-β signaling.

Astrogliosis following spinal cord injury (SCI) was considered as a negative factor for neural regeneration. We found that miR-21 was significantly upregulated after SCI. So, we aim to determine whether miR-21 acts in a positive manner post SCI.

Knockdown of MicroRNA-21 Promotes Neurological Recovery After Acute Spinal Cord Injury.

To assess the therapeutic effects of microRNA-21 (miR-21) knockdown (KD) for acute thoracic spinal cord contusion using a mouse model. Forty C57/BL6 mice were randomly divided into four groups: mice in the sham-operated (Sham) group received surgical procedure without spinal cord contusion; the spinal cord injury (SCI) group mice underwent spinal cord contusion without treatment; mice in the miR-21 KD group underwent spinal cord contusion followed by a single dose subdural injection of miR-21 KD vectors (1 × 10 TU); and the negative control (NC) group mice were given subdural injection of comparable amount of NC vectors (1 × 10 TU) after spinal cord contusion. The Basso Mouse Scale (BMS) was employed to assess hindlimb motor functions.

MicroRNA-21a-5p promotes fibrosis in spinal fibroblasts after mechanical trauma.

Traumatic spinal cord injury (SCI) causes permanent disability to at least 180,000 people per year worldwide. Early regulation of spinal fibroblast proliferation may inhibit fibrotic scar formation, allowing the creation of a favorable environment for neuronal regeneration and thereby enhancing recovery from traumatic SCIs. In this study, we aimed to identify the role of microRNA-21a-5p (miR-21a-5p) in regulating spinal fibroblasts after mechanical trauma and to investigate the dysregulation of miR-21a-5p in the pathological process of spinal SCI.

MicroRNA-21-5p mediates TGF-β-regulated fibrogenic activation of spinal fibroblasts and the formation of fibrotic scars after spinal cord injury.

Little regeneration of transected axons occurs after the damage caused by traumatic spinal cord injury (SCI), and unidirectional and irreversible fibrotic scars are thought to be the main chemical and physical obstacle for axonal regrowth in SCI pathology. We previously demonstrated that microRNA (miR)-21-5p and transforming growth factor (TGF)-β1, a central pathological mediator of fibrotic diseases, were significantly up-regulated in the lesion epicenter after SCI. Here, we found that TGF-β1 enhanced miR-21-5p expression in primary spinal fibroblasts, and regulated the expression of fibrosis-related genes.