Omnidirectional improvement of mitochondrial health in Alzheimer's disease by multi-targeting engineered activated neutrophil exosomes.

Alzheimer's disease (AD) is one kind of devasting neurodegenerative disorders affecting over 50 million people worldwide. Multi-targeted therapy has emerged as a new treatment for diagnosing and alleviating the pathogenesis process of AD; however, the current strategy is limited by its unsatisfactory efficiency. In our study, engineered activated neutrophil-derived exosomes (MP@Cur-MExo) were developed to improve the mitochondrial function in neurons by targeting and alleviating Aβ-induced neurotoxicity.

Mechanical loading on osteocytes regulates thermogenesis homeostasis of brown adipose tissue by influencing osteocyte-derived exosomes.

Background: Osteocytes are the main stress-sensing cells in bone. The substances secreted by osteocytes under mechanical loading play a crucial role in maintaining body homeostasis. Osteocytes have recently been found to release exosomes into the circulation, but whether they are affected by mechanical loading or participate in the regulation of systemic homeostasis remains unclear.

Oncostatin M-driven macrophage-fibroblast circuits as a drug target in autoimmune arthritis.

Background: Recent single-cell RNA sequencing (scRNA-seq) analysis revealed the functional heterogeneity and pathogenic cell subsets in immune cells, synovial fibroblasts and bone cells in rheumatoid arthritis (RA). JAK inhibitors which ameliorate joint inflammation and bone destruction in RA, suppress the activation of various types of cells in vitro. However, the key cellular and molecular mechanisms underlying the potent clinical effects of JAK inhibitors on RA remain to be determined.

Bifunctional TRPV1 Targeted Magnetothermal Switch to Attenuate Osteoarthritis Progression.

Transient receptor potential vanilloid family member 1 (TRPV1) has been revealed as a therapeutic target of osteoarthritis (OA), the most common deteriorating whole joint disease, by impeding macrophagic inflammation and chondrocytes ferroptosis. However, the clinical application for capsaicin as the TRPV1 agonist is largely limited by its chronic toxicity. To address this issue, we developed a bifunctional controllable magnetothermal switch targeting TRPV1 for the alleviation of OA progression by coupling of magnetic nanoparticles (MNPs) to TRPV1 monoclonal antibodies (MNPs-TRPV1).

Effect of JAK inhibitors on the three forms of bone damage in autoimmune arthritis: joint erosion, periarticular osteopenia, and systemic bone loss.

Background: The types of bone damage in rheumatoid arthritis (RA) include joint erosion, periarticular osteoporosis, and systemic osteoporosis. Janus kinase (JAK) inhibitors ameliorate inflammation and joint erosion in RA, but their effect on the three types of bone loss have not been reportedly explored in depth. We aimed to clarify how JAK inhibitors influence the various types of bone loss in arthritis by modulating osteoclastic bone resorption and/or osteoblastic bone formation.

Corrigendum: Influence of lecithin cholesterol acyltransferase alteration during different pathophysiologic conditions: A 45 years bibliometrics analysis.

[This corrects the article DOI: 10.3389/fphar.2022.

Manipulating PP2Acα-ASK-JNK signaling to favor apoptotic over necroptotic hepatocyte fate reduces the extent of necrosis and fibrosis upon acute liver injury.

In the widely used Carbon tetrachloride (CCl)-induced acute liver injury (ALI) mouse model, hepatocytes are known to die from programmed cell death (PCD) processes including apoptosis and necroptosis. Both in vivo and in vitro experiments showed that CCl treatment could induce both apoptosis and necroptosis. Treatment of mice with the apoptosis inducer SMAC mimetic reduced necroptosis, led to less pronounced liver damage, and improved overall liver function.

Atrophic skeletal muscle fibre-derived small extracellular vesicle miR-690 inhibits satellite cell differentiation during ageing.

Background: Sarcopenia is a common and progressive skeletal muscle disorder characterized by atrophic muscle fibres and contractile dysfunction. Accumulating evidence shows that the number and function of satellite cells (SCs) decline and become impaired during ageing, which may contribute to impaired regenerative capacity. A series of myokines/small extracellular vesicles (sEVs) released from muscle fibres regulate metabolism in muscle and extramuscular tissues in an autocrine/paracrine/endocrine manner during muscle atrophy.

Targeting macrophagic SHP2 for ameliorating osteoarthritis TLR signaling.

Osteoarthritis (OA), in which M1 macrophage polarization in the synovium exacerbates disease progression, is a major cause of cartilage degeneration and functional disabilities. Therapeutic strategies of OA designed to interfere with the polarization of macrophages have rarely been reported. Here, we report that SHP099, as an allosteric inhibitor of src-homology 2-containing protein tyrosine phosphatase 2 (SHP2), attenuated osteoarthritis progression by inhibiting M1 macrophage polarization.

Exercised accelerated the production of muscle-derived kynurenic acid in skeletal muscle and alleviated the postmenopausal osteoporosis through the Gpr35/NFκB p65 pathway.

Background: Reduced serum estrogen levels in postmenopausal patients not only aggravate bone loss but also impact myokine secretion. Emerging evidence has revealed the importance of myokines in bone metabolism, and exercise can interfere with the secretion of myokines. However, few studies have explored the impact of exercise on myokine secretion in the postmenopausal osteoporosis (PMOP) process.

The accuracy of an extramedullary femoral cutting system in total knee arthroplasty in patients with severe coronal femoral bowing: a radiographic study.

Background: Intramedullary (IM) femoral alignment instrument is imprecise for the coronal alignment in total knee arthroplasty (TKA) in patients with severe lateral bowing of the femur, while the extramedullary (EM) alignment system does not depend on the structure of the femoral medullary cavity. The aim of this retrospective study was to compare the accuracy of postoperative limb alignment with the two femoral alignment techniques for patients with severe coronal femoral bowing.

Methods: From January 2017 to December 2019, patients with end-stage knee osteoarthritis and coronal femoral bowing angle (cFBA) ≥ 5° who underwent total knee arthroplasty TKA at our institution were enrolled in the study.

Bone targeting antioxidative nano-iron oxide for treating postmenopausal osteoporosis.

Osteoporosis is the most common degenerative orthopedic disease in the elderly. Recently, the therapeutic methods for osteoporosis have shifted towards the regulation of local immunity in bone tissues, which could provide a suitable environment for the positive regulation of bone metabolism, promoting osteogenic differentiation and inhibiting osteoclast differentiation. Our previous work demonstrated that iron oxide nanoparticles (IONPs) could positively regulate bone metabolism .

Defects in a liver-bone axis contribute to hepatic osteodystrophy disease progression.

Hepatic osteodystrophy (HOD) is a metabolic bone disease that is often associated with chronic liver disease and is marked by bone loss. Here, we demonstrate that hepatic expression of the phosphatase PP2Acα is upregulated during HOD, leading to the downregulation of expression of the hepatokine lecithin-cholesterol acyltransferase (LCAT). Loss of LCAT function markedly exacerbates the bone loss phenotype of HOD in mice.

Intraarticular injection of SHP2 inhibitor SHP099 promotes the repair of rabbit full-thickness cartilage defect.

Background: Cartilage repair has been a challenge in the field of orthopaedics for decades, highlighting the significance of investigating potential therapeutic drugs. In this study, we explored the effect of the SHP2 inhibitor SHP099, a small-molecule drug, on cartilage repair.

Methods: Human synovial mesenchymal stem cells (SMSCs) were isolated, and their three-way differentiation potential was examined.

Impaired delay discounting and time sensitivity in methcathinone use disorder.

Substance use disorder (SUD) is characterized by continued drug use despite adverse consequences. Methcathinone is a new type of psychoactive substance that is associated with high excitement and impulsive behaviors. However, it is unclear if individuals with methcathinone use disorders (MCUD) are with impaired decision-making ability.

METTL3-mediated mA modification of ATG7 regulates autophagy-GATA4 axis to promote cellular senescence and osteoarthritis progression.

Objective: The aim of the study was to investigate the role and regulatory mechanisms of fibroblast-like synoviocytes (FLSs) and their senescence in the progression of osteoarthritis (OA).

Methods: Synovial tissues from normal patients and patients with OA were collected. Synovium FLS senescence was analysed by immunofluorescence and western blotting.

Network Pharmacology-Based Strategy for the Investigation of the Anti-Osteoporosis Effects and Underlying Mechanism of Zhuangguguanjie Formulation.

As the society is aging, the increasing prevalence of osteoporosis has generated huge social and economic impact, while the drug therapy for osteoporosis is limited due to multiple targets involved in this disease. Zhuangguguanjie formulation (ZG) is extensively used in the clinical treatment of bone and joint diseases, but the underlying mechanism has not been fully described. This study aimed to examine the therapeutic effect and potential mechanism of ZG on postmenopausal osteoporosis.

The influence of different THA surgical approaches on Patient's early postoperative anxiety and depression.

Introduction: Total hip arthroplasty (THA) is generally considered to be one of the most successful orthopedic surgical procedures. However, no research has been conducted on the postoperative mental health of patients who underwent different approaches of THA. This paper seeks to compare the differences among three THA approaches: the normal lateral approach (NLA), the direct anterior approach (DAA) and the orthopädische chirurgie münchen (OCM) regarding their influence on patients' postoperative anxiety and depression.

Several FDA-Approved Drugs Effectively Inhibit SARS-CoV-2 Infection in vitro.

To identify drugs that are potentially used for the treatment of COVID-19, the potency of 1403 FDA-approved drugs were evaluated using a robust pseudovirus assay and the candidates were further confirmed by authentic SARS-CoV-2 assay. Four compounds, Clomiphene (citrate), Vortioxetine, Vortioxetine (hydrobromide) and Asenapine (hydrochloride), showed potent inhibitory effects in both pseudovirus and authentic virus assay. The combination of Clomiphene (citrate), Vortioxetine and Asenapine (hydrochloride) is much more potent than used alone, with IC50 of 0.

Specific determination of hepatitis B e antigen by antibodies targeting precore unique epitope facilitates clinical diagnosis and drug evaluation against hepatitis B virus infection.

Hepatitis B e antigen (HBeAg) is a widely used marker both for chronic hepatitis B (CHB) clinical management and HBV-related basic research. However, due to its high amino acid sequence homology to hepatitis B core antigen (HBcAg), most of available anti-HBe antibodies are cross-reactive with HBcAg resulting in high interference against accurate measurement of the status and level of HBeAg. In the study, we generated several monoclonal antibodies (mAbs) targeting various epitopes on HBeAg and HBcAg.

Development of a novel polysaccharide-based iron oxide nanoparticle to prevent iron accumulation-related osteoporosis by scavenging reactive oxygen species.

In this work, the biological polysaccharide-based antioxidant polyglucose-sorbitol-carboxymethyl ether (PSC) was used as the precursor to synthesize FeO@PSC nanoparticles, which are expected to scavenge excess reactive oxygen species (ROS) to inhibit osteogenesis and promote osteoclast differentiation in iron accumulation (IA)-related osteoporosis. The FeO@PSC nanoparticles obtained were of a uniform particle size of 7.3 nm with elemental O/Fe/Cl/C at a ratio of 190:7:2:88.

Serum levels of leptin, osteopontin, and sclerostin in patients with and without knee osteoarthritis.

Objective: To investigate the relationship between leptin, osteopontin (OPN), sclerostin (SOST) and severity of knee osteoarthritis (KOA).

Methods: The study included 148 consecutive patients with knee OA and 101 non-KOA subjects enrolled in this cross-sectional study. All patients fulfilled the American College of Rheumatology criteria for primary knee OA.

Trehalose reduces bone loss in experimental biliary cirrhosis rats via ERK phosphorylation regulation by enhancing autophagosome formation.

Bone loss is a severe complication of primary biliary cirrhosis (PBC). Trehalose was intermittently administered in bile duct-ligated (BDL) male rats, a PBC-related osteoporosis model, for 4 weeks to reduce osteoporosis. Femoral bones were assessed ex vivo by micro computed tomography (CT) and histomorphometry.