Osteoporosis, a bone disease resulting in the loss of bone density and microstructure quality, is often associated with fragility fractures, and the latter imposes a great burden on the patient and society. Although there are several different treatments available for osteoporosis such as hormone replacement therapy, bisphosphonates, Denosumab, and parathyroid hormone, some concerns have been raised regarding the inherent side effects of their long term use. It would be of great relevance to search for alternative natural compounds, which could complementarily overcome the limitations of the currently available therapy. Herein, we review current literature on natural compounds that might have therapeutic values for osteoporosis. Search terms included bone resorption, bone density, osteoporosis, postmenopausal, osteoporosis or bone density conservation agents, and any of the terms related to traditional, herbal, natural therapy, natural health, diet, or phytoestrogens. All the compounds and herbs included in the review are naturally bioactive or are used in folk herbal medicine and have been reported to be capable of attenuating osteopenia or osteoporosis in vivo or in vitro, through various mechanisms - estrogen-like activity, antioxidant and anti-inflammatory properties, or by modulating the key signaling pathways in the pathogenesis of osteoporosis. Through our assessment of the therapeutic potential and outlook of alternative medicine, we aim to provide an appealing perspective for the consideration of the application of a complementary anti-osteoporotic treatment option and prevention strategy for osteoporosis or osteolytic bone disorders.
Background: Cell-free DNA (cf-DNA)-based liquid biopsy is emerging as a revolutionary new method in individualized cancer treatment and prognosis monitoring, although detecting early-stage cancers using cf-DNA remains challenging, partially because of the undefined biological background of cf-DNA. Materials and methods: We investigated somatic mutations in the cf-DNA of 259 cancer-free individuals with a median age of 47 years using an endogenous barcoding duplex method with an ultralow base error rate (2 Â 10 À7) and compared the variant allele frequencies (VAFs) of these mutations between the cf-DNA and the corresponding blood cell DNA. Results: Sixty percent (155/259) of the samples showed at least one nonsynonymous mutation on either of two similar target panels covering 508 and 559 cancer-related genes. For individuals older than 50 years of age, the positive rate increased to 76%. Most cf-DNA mutations were also present at similar VAFs in the paired blood cell DNA. The most frequently mutated genes were driver genes of hematologic malignancies, including DNMT3A, TET2, AXSL1, and JAK2. However, the other 58.4% (192/329) of the mutations were likely 'passenger mutations' of clonal hematopoiesis, including mutations in NOTCH2, FAT3, EXT2, ERBB4, and ARID2, which are driver genes of solid tumors. Conclusion: Hematopoietic clone-derived mutations, including 'driver mutations' and 'passenger mutations', are prevalent in the cf-DNA of both healthy individuals and cancer patients and may be a potential source of false positives in the liquid biopsy. Our results also suggest the ineffectiveness for distinguishing clonal hematopoietic mutations of low VAF (0.1%) from tumorderived mutations using conventional next-generation sequencing of blood cell DNA. However, an error correction model with an ultralow error rate and high coverage depth is required for blood cell DNA sequencing, which is difficult and costly to achieve with current technologies.
Objective. Despite an extensive body of research on nonsteroidal antiinflammatory drugs (NSAIDs) in osteoarthritis, the duration of their efficacy and timeline of adverse event (AE) onset have been understudied. We conducted a systematic review and meta-analyses from 2 to 26 weeks to characterize the efficacy and AE trajectories of oral NSAIDs in knee osteoarthritis.Methods. We searched MEDLINE, Embase, Web of Science, Google Scholar, and the Cochrane Database from inception to May 2018. Randomized controlled trials assessing the efficacy and/or safety of Federal Drug Administration-approved NSAIDs in knee osteoarthritis patients were included. Two independent reviewers assessed quality and extracted data. We calculated standardized mean differences (SMDs) and risk ratios (RRs) with 95% confidence intervals (95% CIs).Results. We included 72 randomized controlled trials (26,424 participants). NSAIDs demonstrated moderate, statistically significant effects on pain that peaked at 2 weeks (SMD -0.43 [95% CI -0.48, -0.38]), but the magnitude of the effects decreased over time. The results for function were similar. The incidence of gastrointestinal (GI) AEs was significantly higher in NSAID users than placebo users as early as 4 weeks (RR 1.38 [95% CI 1.21, 1.57]). The incidence of cardiovascular (CV) AEs in NSAID users was not significantly different from placebo. Most GI and CV AEs were transient and of minor severity.Conclusion. NSAIDs produced significant pain and function improvements that peaked at 2 weeks but decreased over time. The incidence of minor GI and CV AEs consistently rose, reaching significance as early as 4 weeks. Clinicians should weigh the durability of efficacy with the early onset of minor AEs along with patient tolerability and preferences when formulating an NSAID regimen.
Aim: To retrospectively investigate the features of renal involvements in patients with primary Sj€ ogren's syndrome (pSS) with biopsy results. Results: One hundred and three pSS nephritis (inpatients had biopsy-proven renal involvement. Tubulointerstitial 53, 51.5%) was the prominent pathologic pattern with glomerulonephritis (GN) present in 50 (48.5%) of the renal lesions. The patterns of GN lesions included membranous nephropathy (37, 35.9%), mesangial proliferative glomerulonephritis (six, 5.8%) or immunoglobulin A nephropathy (three, 2.9%), minimal change disease (four, 3.9%) and focal segmental glomerulosclerosis (three, 2.9%). Compared to SS-only patients, SS-renal patients had fewer dry eyes and positive objective xerostomia (P < 0.05). They presented with a significantly lower incidence of interstitial lung disease (ILD), leukocytopenia and elevated immunoglobulin G levels (P < 0.05). They received a larger initial dosage of corticosteroid and had a higher mortality rate (P < 0.05).Conclusion: This Chinese SS-renal population with biopsy results has diverse pathologic patterns and distinct clinical features. They are characterized with prominent renal-associated and mild SS-associated features. They received more vigorous treatment but had poorer prognosis.
Osteoporosis is a devastating disease that features reduced bone quantity and microstructure, which causes fragility fracture and increases mortality, especially in the aged population. Due to the long-term side-effects of current drugs for osteoporosis, it is of importance to find other safe and effective medications. Ellagic acid (EA) is a phenolic compound found in nut galls, plant extracts, and fruits, and exhibits antioxidant and antineoplastic effects. Here, we showed that EA attenuated the formation and function of osteoclast dose-dependently. The underlying mechanism was further discovered by western blot, immunofluorescence assay, and luciferase assay, which elucidated that EA suppressed osteoclastogenesis and bone resorption mainly through attenuating receptor activator of nuclear factor-κB (NF-κB) ligand-induced NF-κB activation and extracellular signal-regulated kinase signaling pathways, accompanied by decreased protein expression of nuclear factor of activated T-cells calcineurin-dependent 1 and c-Fos. Moreover, EA inhibits osteoclast marker genes expression including Dc-stamp, Ctsk, Atp6v0d2, and Acp5. Intriguingly, we also found that EA treatment could significantly protect ovariectomy-induced bone loss in vivo. Conclusively, this study suggested that EA might have the therapeutic potentiality for preventing or treating osteoporosis. K E Y W O R D S ellagic acid, ERK, NF-κB, osteoclast, osteoporosis, RANKL Xixi Lin and Guixin Yuan contributed equally to this work.
Congenital anomalies of wingless-type mouse mammary tumor virus (MMTV) integration site family (Wnt) are frequently accompanied with tooth and dentin abnormality. The aim of this study was to investigate the effects of Wnt signaling on odontoblast differentiation of mouse dental papilla cells (MDPs). Mouse dental papilla cells were cultured in α-modified minimum essential medium containing 10% fetal bovine serum and antibiotics. Odontoblast differentiation was induced by bone morphogenic protein 2 (BMP2), and the expression of odontoblast-specific markers and Wnt-related signaling molecules was analyzed by real-time reverse transcription-polymerase chain reaction and immunohistochemistry. Odontoblast differentiation was evaluated by dentin sialophosphoprotein (Dspp) and dentin matrix protein (DMP) 1 expression. Localization of β-catenin in MDPs was detected by immunocytochemistry using an anti-β-catenin antibody. Dspp expression in MDPs was upregulated in the presence of BMP2. Wnt5a, Wnt11, Lef1 and Tcf4 expression was upregulated in BMP2-treated MDPs. Wnt11 expression was detected in rat dental pulp in vivo, and particularly strong expression of Wnt11 was detected in odontoblasts. Enhanced Dspp and DMP1 expression and alkaline phosphatase activity induced by BMP2 were completely negated by the Wnt antagonist: IWR-1-endo treatment. Nuclear translocation of β-catenin observed in BMP2-treated MDPs was also negated by IWR-1-endo treatment. These results indicate that Wnt signaling upregulates odontoblast marker expression in MDPs, suggesting a promoting effect of Wnt signaling on odontoblast differentiation.
Photoacoustic imaging (PAI) is an emerging imaging strategy with a unique combination of rich optical contrasts, high ultrasound spatial resolution, and deep penetration depth without ionizing radiation.Taking advantage of the features mentioned above, PAI has been widely applied to preclinical studies in diverse fields, such as vascular biology, cardiology, neurology, ophthalmology, dermatology, gastroenterology, and oncology. Among various biomedical applications, photoacoustic brain imaging has great importance due to the brain's complex anatomy and the variability of brain disease. In this review, we aimed to introduce a novel and effective imaging modality for diagnosing brain diseases. Firstly, a brief overview of two major types of PAI system was provided. Then, PAI's major preclinical applications in brain diseases were introduced, including early diagnosis of brain tumors, subtle changes in the chemotherapy response, epileptic activity and brain injury, foreign body, and brain plaque. Finally, a perspective of the remaining challenges of PAI was given for future advancements.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.