Battling pain from osteoarthritis: causing novel cell death.

Osteoarthritis (OA) is a significant contributor to pain and disability worldwide. Pain is the main complaint of OA patients attending the clinic and has a large impact on their quality of life and economic standards. However, existing treatments for OA-related pain have not been shown to achieve good relief.

ITGB2 fosters the cancerous characteristics of ovarian cancer cells through its role in mitochondrial glycolysis transformation.

Related studies have shown that ITGB2 mediates mitochondrial glycolytic transformation in cancer-associated fibroblasts and participates in tumor occurrence, metastasis and invasion of cancer cells. Based on these studies, we tried to construct a mitochondrial glycolysis regulatory network and explored its effect on mitochondrial homeostasis and ovarian cancer cells' cancerous characteristics. Our research revealed a distinct increase in the expression of ITGB2 and associated signaling pathway elements (PI3K-AKT-mTOR) in cases of ovarian cancer.

ADAM8 silencing suppresses the migration and invasion of fibroblast-like synoviocytes via FSCN1/MAPK cascade in osteoarthritis.

Objective: Osteoarthritis (OA) is a degenerative joint disease that affects elderly populations worldwide, causing pain and disability. Alteration of the fibroblast-like synoviocytes (FLSs) phenotype leads to an imbalance in the synovial inflammatory microenvironment, which accelerates the progression of OA. Despite this knowledge, the specific molecular mechanisms of the synovium that affect OA are still unclear.

κ-Opioid receptor activation attenuates osteoarthritis synovitis by regulating macrophage polarization through the NF-κB pathway.

Osteoarthritis (OA) is a prevalent and chronic joint disease that affects the aging population, causing pain and disability. Macrophages in synovium are important mediators of synovial inflammatory activity and pathological joint pain. Previous studies have demonstrated the significant involvement of κ-opioid receptor (KOR) in the regulation of pain and inflammation.

REPIN1 regulates iron metabolism and osteoblast apoptosis in osteoporosis.

Osteoporosis is not well treated due to the difficulty of finding commonalities between the various types of it. Iron homeostasis is a vital component in supporting biochemical functions, and iron overload is recognized as a common risk factor for osteoporosis. In this research, we found that there is indeed evidence of iron accumulation in the bone tissue of patients with osteoporosis and REPIN1, as an origin specific DNA binding protein, may play a key role in this process.

MAGL inhibition relieves synovial inflammation and pain via regulating NOX4-Nrf2 redox balance in osteoarthritis.

Osteoarthritis (OA) is a degenerative joint disease characterized by cartilage injury, hyperplasia of bone and inflammatory lesions of synovium. Monoacylglycerol lipase (MAGL), a member of the α/β hydrolase superfamily, is involved in regulation of injury protection and immune-inflammation response. Autoinflammatory response of the synovium and the release of inflammatory mediators play critical roles in occurrence of early-stage OA.

LncRNA CACNA1G-AS1 up-regulates FTH1 to inhibit ferroptosis and promote malignant phenotypes in ovarian cancer cells.

Previous study revealed that ferritin heavy chain-1 (FTH1) could regulate ferritinophagy and affect intracellular Fe content in various tumors, while its N6-methyladenosine (m6A) RNA methylation was closely related the prognosis of ovarian cancer patients. However, little is known about the role of FTH1 m6A methylation in ovarian cancer (OC) and its possible action mechanisms. In this study we constructed FTH1 m6A methylation regulatory pathway (LncRNA CACNA1G-AS1/IGF2BP1) according to related bioinformatics analysis and research, through clinical sample detections we found that these pathway regulatory factors were significantly up-regulated in ovarian cancer tissues, and their expression levels were closely related to the malignant phenotype of ovarian cancer.

Dexmedetomidine alleviates osteoarthritis inflammation and pain through the CB pathway in rats.

As a common joint disease, osteoarthritis (OA) is often associated with chronic pain. Synovial inflammation is correlated with OA progression and pain. Synovial inflammation can produce a series of destructive substances, such as inflammatory factors and pain mediators, which aggravate cartilage injury and further accelerate the progression of OA.

The FDX1 methylation regulatory mechanism in the malignant phenotype of glioma.

To explore FDX1 methylation as a regulatory mechanism in the malignant phenotype of glioma, we screened for pathways involved through bioinformatic analysis, then proceeded with RIP and cell models to verify the regulation of RNAs and mitophagy. We chose Clone and Transwell assays to evaluate the malignant phenotype of glioma cells. MMP was detected by flow cytometry and mitochondrial morphology was observed by TEM.

α-Synuclein-Induced Destabilized BMAL1 mRNA Leads to Circadian Rhythm Disruption in Parkinson's Disease.

Circadian dysfunction is a common non-motor symptom in Parkinson's disease (PD). The potential influence of aggravated α-synuclein (SNCA) on circadian disruption remains unclear. SNCA-overexpressing transgenic mice (SNCA mice) and wild-type (WT) littermates were used in this study.

Theaflavin-3,3'-Digallate Ameliorates Collagen-Induced Arthritis Through Regulation of Autophagy and Macrophage Polarization.

Purpose: Previous studies have presented that theaflavin-3,3'-digallate (TFDG), one of natural flavonoids, have protective effects on collagen-induced arthritis (CIA). Besides, it was reported that TFDG could affect inflammatory signaling pathways, like NF-κB, JNK, and so on, to ameliorate inflammation. However, the anti-inflammatory mechanisms mentioned above are common to natural flavonoid products including TFDG.

C-MYC Inhibited Ferroptosis and Promoted Immune Evasion in Ovarian Cancer Cells through NCOA4 Mediated Ferritin Autophagy.

Objective: We aimed to construct the ferritin autophagy regulatory network and illustrate its mechanism in ferroptosis, TME immunity and malignant phenotypes of ovarian cancer.

Methods: First, we used Western blot assays and immunohistochemistry to detect the pathway expression in ovarian cancer samples (C-MYC, NCOA4). Then, we performed RIP and FISH analysis to verify the targeted binding of these factors after which we constructed ovarian cancer cell models and detected pathway regulator expression (NCOA4).

Cardiac involvement in Wilson's disease: a retrospective cohort study.

Background And Objectives: Wilson's disease (WD) is an inherited disorder with perturbations in copper metabolism and can cause multiorgan damage. This study aims to explore cardiac findings mainly based on electrocardiography (ECG) in WD patients.

Methods: We retrospectively enrolled adult patients who were diagnosed with WD between January 2011 and December 2020.

Gut Metabolite Urolithin A Inhibits Osteoclastogenesis and Senile Osteoporosis by Enhancing the Autophagy Capacity of Bone Marrow Macrophages.

Senile osteoporosis (SOP) is a systemic bone disease that is significantly associated with age and eventually leads to deteriorated bone strength and increased fracture risk. Urolithin A (Uro-A) is a gut microbiome-derived compound that is mainly produced from pomegranates and some nuts. Uro-A has attracted great attention in recent years in view of its protective effects on aging-related diseases, including muscle dysfunction, kidney disease and knee injury.

Micro-patterned cell populations as advanced pharmaceutical drugs with precise functional control.

Human cells are both advanced pharmaceutical drugs and 'drug deliverers'. However, functional control prior to or after cell implantation remains challenging. Micro-patterning cells through geometrically defined adhesion sites allows controlling morphogenesis, polarity, cellular mechanics, proliferation, migration, differentiation, stemness, cell-cell interactions, collective cell behavior, and likely immuno-modulatory properties.

Rebalance of the Polyamine Metabolism Suppresses Oxidative Stress and Delays Senescence in Nucleus Pulposus Cells.

Intervertebral disk degeneration (IDD) is a major cause of low back pain that becomes a prevalent age-related disease. However, the pathophysiological processes behind IDD are rarely known. Here, we used bioinformatics analysis based on the microarray datasets (GSE34095) to identify the differentially expressed genes (DEGs) as biomarkers and therapeutic targets in degenerated discs.

miR-34a overexpression protects against hippocampal neuron damage caused by ketamine-induced anesthesia in immature rats through the Notch-1/NF-κB signaling pathway.

Objective: To investigate the protective effect of miR-34a overexpression on hippocampal neuron damage caused by ketamine-induced anesthesia in immature rats and the underlying mechanism.

Methods: A total of 48 male SD rats were divided into control group (CG, n=12), ketamine group (KG, n=12), negative control group (NCG, n=12), and intervention group (IG, n=12) by using the random number table method. Neurological function, cognitive function, pathological changes of brain tissues, inflammatory cytokines, as well as mRNA expression levels of Notch-1, NICD, RBP-JK, and Hes-1 in brain tissues were detected in the four groups.

Urolithin A suppresses RANKL-induced osteoclastogenesis and postmenopausal osteoporosis by, suppresses inflammation and downstream NF-κB activated pyroptosis pathways.

Osteoporosis (OP) is characterized by decreased trabecular bone volume and microarchitectural deterioration in the medullary cavity. Urolithin A (UA) is a biologically active metabolite generated by the gut microbiota. UA is the measurable product considered the most relevant urolithin as the final metabolic product of polyphenolic compounds.

Punicalagin ameliorates collagen-induced arthritis by downregulating M1 macrophage and pyroptosis via NF-κB signaling pathway.

Rheumatoid arthritis (RA) is a chronic inflammatory disease that eventually leads to disability. Inflammatory cell infiltration, severe joint breaking and systemic bone loss are the main clinical symptoms. In this study, we established a collagen-induced arthritis (CIA) model and found a large number of M1 macrophages and pyroptosis, which are important sources of proinflammatory cytokines.

Human bone mesenchymal stem cells-derived exosomal miRNA-361-5p alleviates osteoarthritis by downregulating DDX20 and inactivating the NF-κB signaling pathway.

Osteoarthritis (OA) is a chronic disease featured by joint hyperplasia, deterioration of articular cartilage, and progressive degeneration. Abnormal expression of microRNAs (miRNAs) has been found to be implicated in the pathological process of OA. In this study, the role of miR-361-5p transferred by exosomes derived from human bone mesenchymal stem cells (hBMSCs) in OA was investigated.

The type 2 diabetes mellitus susceptibility gene CDKAL1 polymorphism is associated with depressive symptom in first-episode drug-naive schizophrenic patients.

Background: Patients with schizophrenia have an increased prevalence of type 2 diabetes mellitus that has shown a significant association with the rs7754840 polymorphism in the gene encoding the cyclin-dependent kinase 5 (CDK5) regulatory subunit-associated protein 1-like 1 (CDKAL1).

Objective: To examine whether this polymorphism was involved in the susceptibility in first-episode drug-naive schizophrenic patients (FDSP), and further influenced their clinical symptoms.

Methods: This polymorphism was genotyped in 239 FDSP and 368 healthy controls.

Theaflavin-3,3'-Digallate Promotes the Formation of Osteoblasts Under Inflammatory Environment and Increases the Bone Mass of Ovariectomized Mice.

Postmenopausal osteoporosis is a disease of bone mass reduction and structural changes due to estrogen deficiency, which can eventually lead to increased pain and fracture risk. Chronic inflammatory microenvironment leading to the decreased activation of osteoblasts and inhibition of bone formation is an important pathological factor that leads to osteoporosis. Theaflavin-3,3'-digallate (TFDG) is an extract of black tea, which has potential anti-inflammatory and antiviral effects.

Protective effects of sirtuin 3 on titanium particle-induced osteogenic inhibition by regulating the NLRP3 inflammasome via the GSK-3β/β-catenin signalling pathway.

Periprosthetic osteolysis (PPO) remains the key factor in implant failure and subsequent revision surgery and is mainly triggered by wear particles. Previous studies have shown that inhibition of osteoblastic differentiation is the most widespread incident affecting the interface of trabecular and loosening prostheses. Additionally, the NLRP3 inflammasome is activated by prosthetic particles.

Exosomes derived from miR-155-5p-overexpressing synovial mesenchymal stem cells prevent osteoarthritis via enhancing proliferation and migration, attenuating apoptosis, and modulating extracellular matrix secretion in chondrocytes.

Synovial mesenchymal stem cells (SMSCs) have the potential to attenuate osteoarthritis (OA)-induced injury. The role and mechanism of SMSC-derived exosomes (SMSC-Exos), pivotal paracrine factors of stem cells, in OA-associated injury remain unclear. We aimed to confirm the effect of SMSC-Exos with specific modifications on OA-induced damage and to investigate the potential molecular mechanisms.

Electroacupuncture Alleviates Osteoarthritis by Suppressing NLRP3 Inflammasome Activation in Guinea Pigs.

Osteoarthritis (OA) is an increasingly prevalent disease affecting synovial joints, which includes joint degeneration, inflammation, and joint pain. The activation of nucleotide-binding and oligomerization domain-like receptor containing protein 3 (NLRP3) could promote synovial inflammation. Previous studies have shown that electroacupuncture (EA) has potential anti-inflammatory effect.