A Glutathione-Consuming Bimetallic Nano-Bomb with the Combination of Photothermal and Chemodynamic Therapy for Tumors: An in vivo and in vitro Study.

Background: Chemodynamic therapy (CDT) faces challenges of low catalytic ion efficiency and ROS production. We developed a ROS nano-bomb, Cu/ZIF-8@GA-Fe, to address these issues.

Methods: The nano-bomb was synthesized by doping copper into ZIF-8 and assembling Fe and gallic acid (GA).

Cepharanthine Ameliorates Chondrocytic Inflammation and Osteoarthritis Regulating the MAPK/NF-κB-Autophagy Pathway.

Osteoarthritis is a worldwide joint disease caused by abnormal chondrocytic metabolism. However, traditional therapeutic methods aimed at anti-inflammation for early-stage disease are palliative. In the present study, we demonstrated that cepharanthine (CEP), extracted from the plant , exerted protective medicinal efficacy on osteoarthritis for the first time.

Additive Effect of Parathyroid Hormone and Zoledronate Acid on Prevention Particle Wears-Induced Implant Loosening by Promoting Periprosthetic Bone Architecture and Strength in an Ovariectomized Rat Model.

Implant-generated particle wears are considered as the major cause for the induction of implant loosening, which is more susceptible to patients with osteoporosis. Monotherapy with parathyroid hormone (PTH) or zoledronate acid (ZOL) has been proven efficient for preventing early-stage periprosthetic osteolysis, while the combination therapy with PTH and ZOL has exerted beneficial effects on the treatment of posterior lumbar vertebral fusion and disuse osteopenia. However, PTH and ZOL still have not been licensed for the treatment of implant loosening to date clinically.

The effect of mitochondrial fusion on chondrogenic differentiation of cartilage progenitor/stem cells via Notch2 signal pathway.

Background: Osteoarthritis (OA) is a debilitating disease that inflicts intractable pain, a major problem that humanity faces, especially in aging populations. Stem cells have been used in the treatment of many chronic diseases, including OA. Cartilage progenitor/stem cells (CPSCs) are a type of stem cells with the ability to self- renew and differentiate.

Effects of glutamate and aspartate on prostate cancer and breast cancer: a Mendelian randomization study.

Background: Respectively, prostate cancer (PCa) and breast cancer (BC) are the second most and most commonly diagnosed cancer in men and women, and they account for a majority of cancer-related deaths world-wide. Cancer cells typically exhibit much-facilitated growth that necessitates upregulated glycolysis and augmented amino acid metabolism, that of glutamine and aspartate in particular, which is tightly coupled with an increased flux of the tricarboxylic acid (TCA) cycle. Epidemiological studies have exploited metabolomics to explore the etiology and found potentially effective biomarkers for early detection or progression of prostate and breast cancers.

α-Mangostin inhibits LPS-induced bone resorption by restricting osteoclastogenesis via NF-κB and MAPK signaling.

Background: Excessive osteoclast activation is an important cause of imbalanced bone remodeling that leads to pathological bone destruction. This is a clear feature of many osteolytic diseases such as rheumatoid arthritis, osteoporosis, and osteolysis around prostheses. Because many natural compounds have therapeutic potential for treating these diseases by suppressing osteoclast formation and function, we hypothesized that α-mangostin, a natural compound isolated from mangosteen, might be a promising treatment as it exhibits anti-inflammatory, anticancer, and cardioprotective effects.

Pediatric and adult obesity concerns in female health: a Mendelian randomization study.

Purpose: Adulthood and childhood obesity are both associated with reproductive diseases and gynecological cancers in females. However, the causal factors associated with these observations have yet to be identified. Mendelian randomization is a process that is independent of inverse bias and confounding and can act as a random control trial in which genetic groups are settled during meiosis, thus representing an effective tool with which to investigate causality.

Genetic Associations Between IL-6 and the Development of Autoimmune Arthritis Are Gender-Specific.

Objectives: To find out the genetic association between IL6 and autoimmune arthritis.

Methods: We performed a two-sample Mendelian randomization (MR) study using multiple genome-wide association studies (GWAS) datasets. Furthermore, a sex-stratified MR study was performed to identify sexual dimorphism in the association between IL6 and autoimmune arthritis.

Using Genetic Variants to Evaluate the Causal Effect of Plasma Phospholipid Fatty Acids on Breast Cancer and Prostate Cancer: A Mendelian Randomization Study.

Background: Observational studies indicate that phospholipid fatty acids (FAs) have an impact on the etiology in cancers, but the results are conflicting. We aimed to investigate the causal association of phospholipid FAs with breast cancer and prostate cancer.

Methods: Fourteen single nucleotide polymorphisms (SNPs) were selected as instrumental variables to predict the level of 10 phospholipid FAs from Genome-wide association studies (GWAS).

Sex Steroids and Osteoarthritis: A Mendelian Randomization Study.

Objective: Sex steroids are thought to contribute to the pathogenesis of osteoarthritis (OA). This study investigated the causal role of sex steroids in site- and sex-specific OA and risk of joint replacement surgery using the Mendelian randomization (MR) method.

Methods: Instrumental variables for estradiol, dehydroepiandrosterone sulfate, testosterone (T), and dihydrotestosterone (DHT) were selected.

Virtual screening identified natural Keap1-Nrf2 PPI inhibitor alleviates inflammatory osteoporosis through Nrf2-mir214-Traf3 axis.

Overactive osteoclastogenesis is involved in the inflammatory bone loss and could be target for therapy. Here, we applied transcription factor enrichment analysis using public inflammatory osteolysis datasets and identified Nrf2 as the potential therapeutic target. Additionally, in-silico screening was performed to dig out Nrf2-Keap1 PPI inhibitor and Forsythoside-β was found to be the best-performing PHG compound.

A Mendelian randomization study on the role of serum parathyroid hormone and 25-hydroxyvitamin D in osteoarthritis.

Objective: Serum parathyroid hormone (PTH) and 25-hydroxyvitamin D [25(OH)D] have been demonstrated to be associated with pathogenesis and progression of osteoarthritis (OA). This study aimed to determine the potential causal relationship between serum PTH and 25(OH)D levels and risk of OA.

Design: We applied the two-sample Mendelian randomization (MR) approach to estimate the causal roles of serum PTH and 25(OH)D on OA.

Causal Associations between Serum Urea and Cancer: A Mendelian Randomization Study.

Urea is largely derived from the urea cycle reactions through hepatic detoxification of free ammonia and cleared by urination, and the serum urea level is a crucial medical indicator for measuring the kidney function in patients with nephropathy; however, investigative revelations pointing to the serum urea level as a risk factor for cancer are very scarce, and relevant studies are restricted by potential biases. We aimed to explore the causal relationships of the serum urea level with cancer development by focusing on renal cell carcinoma (RCC) using the Mendelian randomization (MR) analyses. Summary estimates were collected from the inverse-variance weighted (IVW) method based on six single nucleotide polymorphisms (SNPs).

Relationship between Serum Nutritional Factors and Bone Mineral Density: A Mendelian Randomization Study.

Purpose: Multiple risk factors have been implicated in the development of osteoporosis. This study examined potential associations between serum nutritional factors and bone mineral density (BMD).

Methods: Six nutritional factors were selected as exposures.

Genetically Predicted Sex Hormone-Binding Globulin and Bone Mineral Density: A Mendelian Randomization Study.

Previous observational studies have identified various risk factors associated with the development of osteoporosis, including sex hormone-binding globulin (SHBG). The aim of this study was to determine the potential causal effects of circulating SHBG concentrations on bone mineral density (BMD). Two-sample Mendelian randomization (MR) approach was applied in analyses.

Parathyroid Hormone and Bone Mineral Density: A Mendelian Randomization Study.

Purpose: Accumulating evidence implicates parathyroid hormone (PTH) in the development of osteoporosis. However, the causal effect of PTH on bone mineral density (BMD) remains unclear. Thus, this study is aimed at exploring the association between the concentrations of serum PTH and BMD.

Sex hormone-binding globulin and arthritis: a Mendelian randomization study.

Background: Sex hormone-binding globulin (SHBG) has been reported to be a risk factor associated with the development of arthritis by previous observational studies more so of three common forms of arthritis: osteoarthritis (OA), rheumatoid arthritis (RA), and ankylosing spondylitis (AS). This study aimed to determine whether the concentrations of circulating SHBG are causally associated with the risk of OA, RA, and AS.

Methods: The two-sample Mendelian randomization (MR) approach was used for this study.

Catalpol suppresses osteoclastogenesis and attenuates osteoclast-derived bone resorption by modulating PTEN activity.

Excessive activation of osteoclast activity is responsible for many bone diseases, such as osteoporosis, rheumatoid arthritis, periprosthetic osteolysis, and periodontitis. Natural compounds that inhibit osteoclast formation and/or function have therapeutic potential for treating these diseases. Catalpol, a bioactive iridoid extracted from a traditional herbal medicine Rehmannia glutinosa, exhibits various pharmacological properties, including anti-inflammatory, antioxidant, antidiabetic, and antitumor effects.

Stachydrine prevents LPS-induced bone loss by inhibiting osteoclastogenesis via NF-κB and Akt signalling.

Osteoclast overactivation-induced imbalance in bone remodelling leads to pathological bone destruction, which is a characteristic of many osteolytic diseases such as rheumatoid arthritis, osteoporosis, periprosthetic osteolysis and periodontitis. Natural compounds that suppress osteoclast formation and function have therapeutic potential for treating these diseases. Stachydrine (STA) is a bioactive alkaloid isolated from Leonurus heterophyllus Sweet and possesses antioxidant, anti-inflammatory, anticancer and cardioprotective properties.

Dehydrocostus lactone attenuates osteoclastogenesis and osteoclast-induced bone loss by modulating NF-κB signalling pathway.

Osteolysis is characterized by overactivated osteoclast formation and potent bone resorption. It is enhanced in many osteoclast-related diseases including osteoporosis and periprosthetic osteolysis. The shortage of effective treatments for these pathological processes emphasizes the importance of screening and identifying potential regimens that could attenuate the formation and function of osteoclasts.

Low-intensity pulsed ultrasound inhibits RANKL-induced osteoclast formation via modulating ERK-c-Fos-NFATc1 signaling cascades.

Low-intensity pulsed ultrasound (LIPUS), which is a noninvasive form of mechanical energy, has been utilized as a clinical therapy for bone fracture healing. However, the mechanism how LIPUS affects osteoclast formation and osteoclast activity, has not been fully detailed. Here we found that LIPUS inhibited RANKL-induced osteoclast differentiation in vitro, characterized by decreased number and area of tartrate-resistant acid phosphatase (TRAP) positive cells.

Stevioside Prevents Wear Particle-Induced Osteolysis by Inhibiting Osteoclastogenesis and Inflammatory Response via the Suppression of TAK1 Activation.

Aseptic loosening and periprosthetic osteolysis are the leading causes of total joint arthroplasty failure, which occurs as a result of chronic inflammatory response and enhanced osteoclast activity. Here we showed that stevioside, a natural compound isolated from , exhibited preventative effects on titanium particle-induced osteolysis in a mouse calvarial model. Further histological assessment and real-time PCR analysis indicated that stevioside prevented titanium particle-induced osteolysis by inhibiting osteoclast formation and inflammatory cytokine expression .

A novel anti-osteoporotic agent that protects against postmenopausal bone loss by regulating bone formation and bone resorption.

Aims: Postmenopausal osteoporosis is a bone metabolism disease that is caused by an imbalance between bone-resorbing osteoclast and bone-forming osteoblast actions. Herein, we describe the role of troxerutin (TRX), a trihydroxyethylated derivative of rutin, in ovariectomy (OVX)-induced osteoporosis and its effects on the regulation of osteoclasts and osteoblasts.

Main Methods: In vivo, OVX female mice were intraperitoneally injected with either saline, 50 mg/kg TRX, or 150 mg/kg TRX for 6 weeks and then sacrificed for micro-computed tomography analyses, histological analyses, and biomechanical testing.

Artemether attenuates LPS-induced inflammatory bone loss by inhibiting osteoclastogenesis and bone resorption via suppression of MAPK signaling pathway.

Osteolysis is an osteolytic lesion featured by enhanced osteoclast formation and potent bone erosion. Lacking of effective regimen for treatment of the pathological process highlights the importance of identifying agents that can suppress the differentiation and function of osteoclast. Artemether is a natural compound derived from Artemisia annua L.