Elevated level of circulating calprotectin correlates with severity and high mortality in patients with COVID-19.

BACKGROUND: Patients with coronavirus disease-2019 (COVID-19) are characterized by hyperinflammation. Calprotectin (S100A8/S100A9) is a calcium- and zinc-binding protein mainly secreted by neutrophilic granulocytes or macrophages and has been suggested to be correlated with the severity and prognosis of COVID-19. AIM: To thoroughly evaluate the diagnostic and prognostic utility of calprotectin in patients with COVID-19 by analyzing relevant studies. METHODS: PubMed, Web of Science, and Cochrane Library were comprehensively searched from inception to August 1, 2023 to retrieve studies about the application of calprotectin in COVID-19. Useful data such as the level of calprotectin in different groups and the diagnostic efficacy of this biomarker for severe COVID-19 were extracted and aggregated by using Stata 16.0 software. RESULTS: Fifteen studies were brought into this meta-analysis. First, the pooled standardized mean differences (SMDs) were used to estimate the differences in the levels of circulating calprotectin between patients with severe and non-severe COVID-19. The results showed an overall estimate of 1.84 (95% confidence interval [CI]: 1.09-2.60). Diagnostic information was extracted from 11 studies, and the pooled sensitivity and specificity of calprotectin for diagnosing severe COVID-19 were 0.75 (95% CI: 0.64-0.84) and 0.88 (95% CI: 0.79-0.94), respectively. The AUC was 0.89 and the pooled DOR was 18.44 (95% CI: 9.07-37.51). Furthermore, there was a strong correlation between elevated levels of circulating calprotectin and a higher risk of mortality outcomes in COVID-19 patients (odds ratio: 8.60, 95% CI: 2.17-34.12; p < 0.1). CONCLUSION: This meta-analysis showed that calprotectin was elevated in patients with severe COVID-19, and this atypical inflammatory cytokine might serve as a useful biomarker to distinguish the severity of COVID-19 and predict the prognosis.

Efficacy and safety of extracorporeal shockwave therapy in chronic low back pain: a systematic review and meta-analysis of 632 patients.

BACKGROUND: Extracorporeal shock wave therapy (ESWT) has been widely used for pain control in musculoskeletal disorders. Whether ESWT can relieve chronic low back pain (CLBP) and improve lumbar function is still unclear. Therefore, we conducted a meta-analysis of relevant studies to comprehensively analyse and determine the efficacy and safety of ESWT for chronic low back pain. METHODS: Four databases were systematically searched for randomized controlled trials (RCTs) on ESWT for CLBP. The quality of the included studies was evaluated according to Cochrane systematic review criteria, relevant data were extracted, and meta-analysis was performed using RevMan 5.4 software. The primary outcomes were pain intensity, disability status, and mental health. The data were expressed as standardized mean differences (SMD) or weighted mean difference (WMD) and 95% confidence intervals (CI). Heterogeneity was assessed using the I2 statistic. If I2 ≥ 50%, a random effects model was applied; otherwise, a fixed effects model was used. RESULTS: Twelve RCTs involving 632 patients were included in this meta-analysis. The ESWT group reported significantly more pain relief than the control group at 4 weeks (WMD = - 1.04; 95% CI = - 1.44 to - 0.65; P < 0.001) and 12 weeks (WMD = - 0.85; 95% CI = - 1.30 to - 0.41; P < 0.001). Regarding the dysfunction index, ESWT led to significant improvement in lumbar dysfunction compared with the control group at 4 weeks (WMD = - 4.22; 95% CI = - 7.55 to - 0.89; P < 0.001) and 12 weeks (WMD = - 4.51; 95% CI = - 8.58 to - 0.44; P = 0.03). For mental health, there was no significant difference between the ESWT group and the control group after 4 weeks of intervention (SMD = 1.17; 95% CI = - 0.10 to 2.45; P = 0.07). CONCLUSION: This systematic review and meta-analysis found that ESWT provided better pain relief and improved lumbar dysfunction compared with the other interventions included, and no serious adverse effects were found. There was no significant effect of ESWT on the mental health of patients, but we hope to obtain more RCTs for further analysis in the future. Based on the pooled results, we suggest that ESWT is effective and safe for treating chronic low back pain.

Berberine inhibits the growth of osteosarcoma through modulating MMP/NM-23 and MAPK/JNK signal pathways.

OBJECTIVE: To investigate the effects and mechanisms of berberine (BBR) on the migration, invasion, proliferation and apoptosis of osteosarcoma cells in vitro. METHODS: Proliferation of MG-63 and U2OS cells was measured by the CCK-8 assay. Cells migration was examined by wound-healing assay. The invasion and metastasis of cells were evaluated by transwell invasion assay. Cells apoptosis was determined by the flow cytometry. Caspase-3 activity in MG-63 and U2OS cells was measured, and Western blot was used to measure the levels of Bax, Bcl-2, MMP-2 and MMP-9 in cells. In addition, the osteosarcoma graft tumor model of mice was established. The tumorigenesis of MG-63 cells in nude mice was compared among three groups. Immunohistochemistry assay was used to measure the levels of MMP-2, MMP-9 and NM-23 in tumor tissue. RESULTS: It was showed that BBR inhibited the proliferation of MG-63 and U2OS cells in vitro in time- and concentration-dependent manners. Moreover, BBR reduced the cells migration and invasion, also down-regulated the expressions of MMP-2 and MMP-9. BBR also inhibited the cells apoptosis by down-regulating the expression of Bcl-2 and up-regulating the expression of Bax. In nude mice, BBR obviously inhibited the tumorigenesis of MG-63 cells. Compared with the negative group, BBR decreased the levels of MMP-2 and MMP-9 and increased the level of NM-23. The molecular mechanism was associated with activation of the MAPK/JNK signal transduction pathway. CONCLUSIONS: BBR significantly regulates the biological behaviors of osteosarcoma cells and inhibits the growth of osteosarcoma. The molecular mechanism may be associated with the modulation of MMP/NM-23 and MAPK/JNK signals. BBR may be a potential drug for the treatment of osteosarcoma.

Cinnamon cassia oil chitosan nanoparticles: Physicochemical properties and anti-breast cancer activity.

The aim of this study was to prepare Cinnamomum cassia essential oil (CEO) impregnated chitosan nanoparticles (CS-CEO) and assess its pharmacological activity against breast cancer. Cinnamon oil-loaded chitosan nanoparticles were investigated for their physicochemical properties, stability, and anti-cancer activities both in vitro and in vivo. The prepared CS-CEO nanoparticles have a particle size, zeta-potential, entrapment efficiency and drug loading of (215.40 ± 3.90) nm, (51.70 ± 1.90) mV, (83.37 ± 0.4)% and (26.42 ± 0.65)%, respectively. CS-CEO showed a regular, uniform, and spherical or quasi-spherical structure under a transmission electron microscope. CS-CEO remained stable upon storage at 4 °C. CS-CEO exhibited enhanced in vitro antitumor activity (52 µg/mL) compared to CEO. The mechanism might be related to the up-regulation of Caspase-3 and AIF protein expression. In in vivo experiments, CS-CEO suppressed the growth of 4T1 breast cancer cells transplanted into mice, inhibited tumor cell proliferation, and induced apoptosis by reducing the expression of the Ki-67 protein. These results indicated that CEO encapsulated in chitosan had a higher physical stability and was also more effective against 4T1 breast tumor model, which can be used as a reference for the application of volatile oil components in traditional Chinese medicine.

Development and Testing of a 5G Multichannel Intelligent Seismograph Based on Raspberry Pi.

A seismograph was designed based on Raspberry Pi. Although comprising 8 channels, the seismograph can be expanded to 16, 24, or 32 channels by using a USB interfacing with a microcontroller. In addition, by clustering more than one Raspberry Pi, the number of possible channels can be extended beyond 32. In this study, we also explored the computational intelligence of Raspberry Pi for running real-time systems and multithreaded algorithms to process raw seismic data. Also integrated into the seismograph is a Huawei MH5000-31 5G module, which provided high-speed internet real-time operations. Other hardware peripherals included a 24 bit ADS1251 analog-to-digital converter (ADC) and a STM32F407 microcontroller. Real-time data were acquired in the field for ambient noise tomography. An analysis tool called spatial autocorrelation (SPAC) was used to analyze the data, followed by inversion, which revealed the subsurface velocity of the site location. The proposed seismograph is prospective for small, medium, or commercial data acquisition. In accordance with the processing power and stability of Raspberry Pi, which were confirmed in this study, the proposed seismograph is also recommended as a template for developing high-performance computing applications, such as artificial intelligence (AI) in seismology and other related disciplines.

The tumor suppressive role of TIMP3 in the human osteosarcoma cells.

BACKGROUND: Tissue inhibitor of metalloproteinase 3 (TIMP3) regulates a variety of cellular activities such as proliferation, viability, apoptosis, and motility. Functional loss of TIMP3 is reported in several human cancers. However, its role in osteosarcoma (OS) remains largely unclear. METHODS: In this study, we explored the mechanism underlying the modulation of TIMP3 in the growth and aggressiveness of U2OS and 143B human OS cells at both cellular and molecular levels. RESULTS: Our results show that overexpression of TIMP3 inhibits endogenous MMP activity and represses a series of oncogenic phenotypes of tumor cells independent of MMP inhibition, including reduced proliferation and survival, induced apoptosis, as well as improved sensitivity of tumor cells in response to cisplatin chemotherapy. TIMP3 overexpression also suppresses tumor cell invasion via its MMP inhibitory capacity. Importantly, TIMP3 modulates tumor cell oncogenesis via its induction of PTEN and subsequent inactivation of the PI3K/AKT pathway. CONCLUSION: Our results suggest that TIMP3 is an oncosuppressor in human OS cells. Reactivation of TIMP3 function may be considered as a potential therapy for the treatment of this bone cancer.

Research Progress of Essential Oil as a New Complementary Therapy in the Treatment of Depression.

Depression is a mood disorder or affective disorder disease with depression as the main symptom. It has become a kind of mental disease that cannot be ignored in the world that seriously endangers human physical and mental health. Antidepressants commonly used in clinics generally have some defects, including slow action, unremarkable effects, and large side-effects. Therefore, there has a huge developing space for the research of new and effective therapeutic drugs to supplement or replace traditional drugs. The essential oil has obvious advantages in the treatment of depression and other emotional diseases, its aromatic odor can directly stimulate the olfactory nerves, and the lipophilic small- molecular compounds can cross the blood-brain barrier easily to play its regulatory role of releasing neurotransmitters and hormones related to depression, or adjusting the expression of brain-derived neurotrophic factor and proinflammatory cytokines. The pathogenesis of depression and the problems in traditional medication were illustrated, the research on the antidepressant effects and mechanism of essential oils in recent years is summarized, and the antidepressant chemical components in plant essential oils are reviewed in this article. The article provides scientific basis for an essential oil to be a new choice for relieving depression and treating depression.

Critical implication of the PTEN/PI3K/AKT pathway during BMP2-induced heterotopic ossification.

Heterotopic ossification (HO) is characterized by extraskeletal ossification in soft tissue. Thus far, there is a lack of effective drug therapy against HO. Loss of PTEN in osteoblasts has been reported to accumulate bone mass in skeletal development and promote fracture healing in association with the activation of the PI3K/AKT pathway. However, the role of the PTEN/PI3K/AKT signaling in HO pathogenesis remains unknown. The present study investigated the implication of this pathway during BMP2­induced osteogenic differentiation and ectopic bone formation. It was shown that overexpression of PTEN inhibited proliferation but stimulated apoptosis in mesenchymal pluripotent C3H10T1/2 cells. PTEN also inhibited BMP2­induced osteoblast differentiation, whereas BMP2 repressed PTEN expression and subsequently activated PI3K/AKT. The PI3K inhibitor, LY294002, blocked BMP2­induced osteoblastogenesis, suggesting that the PI3K/AKT pathway is critically required for BMP2 to initiate osteoblastogenesis. In vivo, implantation of BMP2 in muscle induced ectopic endochondral ossification. Strikingly, this bone­forming capacity was notably suppressed by the PI3K inhibitor LY294002. Hence, the results of the present study demonstrated that the PI3K/AKT signaling activity is indispensable for BMP2 to induce ectopic new bone. Targeting the PI3K/AKT pathway using inhibitor(s) may represent a potential molecular therapy for the treatment against HO.

Traditional Chinese herbal medicine Astragalus Radix and its effects on intestinal absorption of aconite alkaloids in rats.

Objective: Astragalus Radix (AR, Huangqi in Chinese) has been widely used as a qi (energy) restoring herb that is thought to act through reinvigorating the spleen and lung. Aconite is used to rebalance the body temperature during illness and played an irreplaceable role in disease control since ancient times, but it is limited by its strong neuro and cardiotoxicity. Since the Song Dynasty (1227), the two herbs have been commonly used as herbal pairs including in the famous Qifu Decotion, from the "Wei's Family Prescription". However, many ancient texts also record that they are not compatible using together, suggesting they can have negative outcomes when mixed. This study investigated whether Astragali Radix had either positive or negative effects on absorption of six different active alkaloids derived from aconite. Methods: Single intestinal perfusion model was used to study the effects of Astragali Radix on aconite alkaloids absorption. Response of ABC transporters and distribution of three tight junction proteins on the surface of intestinal enothelium were assessed by Reverse Transcription-Polymerase Chain Reaction (RT-PCR), Western blot and immunofluorescence microscopy, respectively. Results: The results showed that aconite alkaloids absorption could be inhibited, and different concentrations of Astragali Radix considerably increased the expression levels of the ABC transporters and tight junction proteins with Astragali Radix treatment. Conclusion: These results suggest that Astragali Radix can block absorption of aconite alkaloids through the upregulation expression of ATP-binding cassette transporters (ABC transporters) and tight junction proteins. It demonstrates that co-administration of Astragali Radix with other drugs might change the absorption profile of the second drug which is important to know in clinic therapy.

Selective Ablation of Descending Serotonin from the Rostral Ventromedial Medulla Unmasks Its Pro-Nociceptive Role in Chemotherapy-Induced Painful Neuropathy.

PURPOSE: Chemotherapy-induced painful neuropathy (CIPN) is a severe adverse effect of many anti-neoplastic drugs that is difficult to manage. Serotonin (5-hydroxytryptamine, 5-HT) is an important neurotransmitter in the rostral ventromedial medulla (RVM), which modulates descending spinal nociceptive transmission. However, the influence of the descending 5-HT from the RVM on CIPN is poorly understood. We investigated the role of 5-HT released from descending RVM neurons in a paclitaxel-induced CIPN rat model. METHODS: CIPN rat model was produced by intraperitoneally injecting of paclitaxel. Pain behavioral assessments included mechanical allodynia and heat hyperalgesia. 5-HT content was analyzed by high-performance liquid chromatography (HPLC). Western blot and immunohistochemistry were used to determine tryptophan hydroxylase (Tph) and c-Fos expression. The inhibitors p-chlorophenylalanine (PCPA) and SB203580 were administrated by stereotaxical RVM microinjection. Ondansetron was injected through intrathecal catheterization. RESULTS: The results demonstrated that Tph, the rate-limiting enzyme in 5-HT synthesis, was significantly upregulated in the RVM, and that spinal 5-HT release was increased in CIPN rats. Intra-RVM microinjection of Tph inhibitor PCPA significantly attenuated mechanical and thermal pain behavior through Tph downregulation and decreased spinal 5-HT. Intra-RVM administration of p38 mitogen-activated protein kinase (p38 MAPK) inhibitor SB203580 alleviated paclitaxel-induced pain in a similar manner to PCPA. Intrathecal injection of ondansetron, a 5-HT3 receptor antagonist, partially reversed paclitaxel-induced pain, indicating that 5-HT3 receptors were involved in descending serotoninergic modulation of spinal pain processing. CONCLUSION: The results suggest that activation of the p38 MAPK pathway in the RVM leads to increased RVM Tph expression and descending serotoninergic projection to the spinal dorsal horn and contributes to the persistence of CIPN via spinal 5-HT3 receptors.

Dkk1 acts as a negative regulator in the osteogenic differentiation of the posterior longitudinal ligament cells.

Ossification of the posterior longitudinal ligament (OPLL) is a spinal disorder characterized by progressive ectopic bone formation in the PLL of the spine. Dickkopf-1 (Dkk1) is a secreted inhibitor of the Wnt pathway that negatively regulates bone formation during skeletal development. However, whether Dkk1 impacts the pathogenesis of OPLL has not been reported. This study is to investigate the role of Dkk1 in the development of OPLL. Our results show that the serum levels of Dkk1 are decreased in OPLL patients compared with non-OPLL controls. The expression of Dkk1 is also reduced in OPLL ligament cells. Downregulation of Dkk1 in ligament cells is associated with activation of the Wnt/ß-catenin signaling, as indicated by stabilized ß-catenin and increased T-cell factor-dependent transcriptional activity. Functionally, Dkk1 exerts a growth-inhibitory effect by repressing proliferation but promoting apoptosis of ligament cells. Dkk1 also suppresses bone morphogenetic protein 2-induced entire osteogenic differentiation of ligament cells, and this suppression is mediated via its inhibition of the Wnt pathway. Our results demonstrate for the first time that Dkk1 acts as an important negative regulator in the ossification of the PLL. Targeting the Wnt pathway using Dkk1 may represent a potential therapeutic strategy for the treatment of OPLL.

A New Cable-Less Seismograph with Functions of Real-Time Data Transmitting and High-Precision Differential Self-Positioning.

This study developed a new cable-less seismograph system, which can transmit seismic data in real-time and automatically perform high-precision differential self-positioning. Combining the ZigBee technology with the high-precision differential positioning module, this new seismograph system utilized the wireless personal area network (WPAN) and real-time kinematic (RTK) technologies to improve its on-site performances and to make the field quality control (QC) and self-positioning possible. With the advantages of low-cost, good scalability, and good compatibility, the proposed new cable-less seismograph system can improve the field working efficiency and data processing capability. It has potential applications in noise seismology and mobile seismic monitoring.

Circular RNA circ_0011269 sponges miR-122 to regulate RUNX2 expression and promotes osteoporosis progression.

Circular RNAs (circRNAs) are a novel class of noncoding RNAs that are widely expressed in human disease. However, circRNAs expression profile and potential mechanism in osteoporosis pathogenesis remain to be further studied. In the present study, a total of 69 circRNAs were identified to be abnormally expressed in osteoporosis patient samples by microarray and bioinformatics analyses. We found that circ_0011269 was notably downregulated in osteoporosis (fold change, 3.94). By means of miRanda algorithm, we constructed the interaction network of circ_0011269-miRNAs in osteoporosis based on target binding and miR-122 was enrolled in the network. Dual-luciferase reporter assay verified the target relationship of miR-122 and circ_0011269/RUNX2. The expression of circ_0011269 and RUNX2 were gradually increased during osteogenic differentiation while miR-122 exhibited a decreased expression. Moreover, overexpression of circ_0011269 could promote RUNX2 expression and inhibit osteoporosis. In summary, this study found that circ_0011269 sponges miR-122 to regulate RUNX2 expression and promotes osteoporosis progression.

The PI3K/AKT pathway promotes fracture healing through its crosstalk with Wnt/ß-catenin.

PI3K/AKT is one of the key pathways that regulate cell behaviors including apoptosis, proliferation, and differentiation. Although previous studies have demonstrated that this pathway is a crucial regulator of osteoblasts, the role of PI3K/AKT in fracture healing remains unclear. It is well known that the Wnt/ß-catenin pathway plays an essential role in bone regeneration. However, whether there exists crosstalk between Wnt/ß-catenin and PI3K/AKT in regulating osteoblasts and bone repair has not been reported. To address these issues, we establish a stabilized fracture model in mice and show that PI3K inhibitor LY294002 substantially inhibits the bone healing process, suggesting that PI3K/AKT promotes fracture repair. More importantly, we report that PI3K/AKT increases phosphorylation of GSK-3ß at Ser9 and phosphorylation of ß-catenin at Ser552 in fracture callus and murine osteoblastic MC3T3-E1 cells, both of which lead to ß-catenin stabilization, nuclear translocation, as well as ß-catenin-mediated TCF-dependent transcription, suggesting that ß-catenin is activated downstream of PI3K/AKT. Furthermore, we show that ICG001, the inhibitor of ß-catenin transcriptional activity, attenuates PI3K/AKT-induced osteoblast proliferation, differentiation, and mineralization, indicating that the PI3K/AKT/ß-catenin axis is functional in regulating osteoblasts. Notably, the PI3K/AKT pathway is also activated by Wnt3a and is involved in Wnt3a-induced osteoblast proliferation and differentiation. Hence, our results reveal the existence of a Wnt/PI3K/AKT/ß-catenin signaling nexus in osteoblasts, highlighting complex crosstalk between PI3K/AKT and Wnt/ß-catenin pathways that are critically implicated in fracture healing.

miR-522 stimulates TGF-ß/Smad signaling pathway and promotes osteosarcoma tumorigenesis by targeting PPM1A.

Osteosarcoma (OS) is identified as an aggressive malignancy of the skeletal system and normally occurs among young people. It is well accepted that microRNAs are implicated in biological activities of diverse tumors. Although miR-522 has been proved to elicit oncogenic properties in a wide range of human cancers, the physiological function and latent mechanism of miR-522 in OS tumorigenesis remain largely to be probed. In the current study, we certified that miR-522 was highly expressed in OS cells and presented carcinogenic function by contributing to cell proliferation, migration, and EMT progression whereas dampening cell apoptosis. In addition, miR-522 provoked TGF-ß/Smad pathway through targeting PPM1A. Finally, the results of mechanism experiments elucidated that miR-522 stimulated TGF-ß/Smad pathway to induce the development of OS via targeting PPM1A, which exposed that miR-522 may become a promising curative target for OS patients.

The Molecular Differentiation of Anatomically Paired Left and Right Mantles of the Pacific Oyster Crassostrea gigas.

Left-right (L-R) asymmetry is controlled by gene regulation pathways for the L-R axis, and in vertebrates, the gene Pitx2 in TGF-ß signaling pathway plays important roles in the asymmetrical formation of organs. However, less is known about the asymmetries of anatomically identical paired organs, as well as the transcriptional regulation mechanism of the gene Pitx in invertebrates. Here, we report the molecular biological differences between the left and right mantles of an invertebrate, the Pacific oyster Crassostrea gigas, and propose one possible mechanism underlying those differences. RNA sequencing (RNA-seq) analysis indicated that the paired organs showed different gene expression patterns, suggesting possible functional differences in shell formation, pheromone signaling, nerve conduction, the stress response, and other physiological processes. RNA-seq and real-time qPCR analysis indicated high right-side expression of the Pitx homolog (cgPitx) in oyster mantle, supporting a conserved role for Pitx in controlling asymmetry. Methylation-dependent restriction-site associated DNA sequencing (MethylRAD) identified a methylation site in the promoter region of cgPitx and showed significantly different methylation levels between the left and right mantles. This is the first report, to our knowledge, of such a difference in methylation in spiralians, and it was further confirmed in 18 other individuals by using a pyrosequencing assay. The miRNome analysis and the TGF-ß receptor/Smad inhibition experiment further supported that several genes in TGF-ß signaling pathway may be related with the L/R asymmetry of oyster mantles. These results suggested that the molecular differentiation of the oyster's paired left and right mantles is significant, TGF-ß signaling pathway could be involved in establishing or maintaining the asymmetry, and the cgPitx gene as one of genes in this pathway; the different methylation levels in its promoter regions between L/R mantles was the one of possible mechanisms regulating the left-right functional differentiation.

The effect of noncoherent red light irradiation on proliferation and osteogenic differentiation of bone marrow mesenchymal stem cells.

Mesenchymal stem cells (MSCs) are promising for use in regenerative medicine. Low-level light irradiation (LLLI) has been shown to modulate various processes in different biological systems. The aim of our study was to investigate the effect of red light emitted from a light-emitting diode (LED) on bone marrow MSCs with or without osteogenic supplements. MSCs both with and without osteogenic supplements were divided into four groups, and each group was irradiated at doses of 0, 1, 2 and 4 J/cm(2). Cellular proliferation was evaluated using WST-8 and 5-ethynyl-2'-deoxyuridine (EdU) fluorescence staining. The alkaline phosphatase activity, mineralization, and expression of osteoblast master genes (Col1α1, Alpl, Bglap and Runx2) were monitored as indicators of MSC differentiation towards osteoblasts. In groups without osteogenic supplements, red light at all doses significantly stimulated cellular proliferation, whereas the osteogenic phenotype of the MSCs was not enhanced. In groups with osteogenic supplements, red light increased alkaline phosphatase activity and mineralized nodule formation, and stimulated the expression of Bglap and Runx2, but decreased cellular proliferation. In conclusion, nonconherent red light can promote proliferation but cannot induce osteogenic differentiation of MSCs in normal media, while it enhances osteogenic differentiation and decreases proliferation of MSCs in media with osteogenic supplements.

The poly(ADP-ribose) polymerase-1 inhibitor 3-aminobenzamide suppresses cell growth and migration, enhancing suppressive effects of cisplatin in osteosarcoma cells.

Pharmacological inhibition of DNA repair pathways has been emerging as an effective tool for cancer treatment. Poly(ADP-ribose) polymerase (PARP) is involved in DNA repair and transcriptional regulation and is now recognized as a key regulator of cell survival and cell death. In vitro and in vivo data suggest that PARP inhibitors could be used not only as chemo/radiotherapy sensitizers but also as single agents to selectively kill cancer cells in certain types of tumors. In the present study, we investigate the effects of 3-aminobenzamide (3-AB), a potent inhibitor of PARP, on human osteosarcoma cells and whether or not it can sensitize the tumor cells to chemotherapeutic agents. The results indicated that 3-AB suppressed U2OS cell growth in a time- and dose-dependent manner, and the suppressive effects of 3-AB were associated with increased cell apoptosis. In addition, 3-AB suppressed cell invasion in vitro and enhanced the suppressive effects of cisplatin in U2OS cells. Our work suggests that this PARP-1 inhibitor may be developed into an effective agent for the treatment of human osteosarcoma.