Current career situations of Chinese pharmacovigilance professionals working for pharmaceutical companies: an exploratory survey.

BACKGROUND: Pharmacovigilance in China has experienced rapid development in the past 30 years. The implementation of Good Pharmacovigilance Practice in China since the end of 2021 heralds a new era of pharmacovigilance affairs, which puts forward higher requirements for the quantity and quality of pharmacovigilance personnel. This study aimed to preliminarily explore the current career situations of pharmacovigilance professionals working in China for pharmaceutical companies. METHODS: A questionnaire was adapted from research in the USA and Europe with the help of several pharmacovigilance experts. Snowball sampling was used to conduct an exploratory survey to obtain the frequency of basic demographic information, work status, and career expectations of pharmacovigilance professionals working for pharmaceutical companies. RESULTS: The personnel engaged in pharmacovigilance work for pharmaceutical companies were mainly medical or pharmaceutical undergraduates within 3 years of graduation. Their work intensity and pressure were relatively high. The training provided by their universities and enterprises could not well meet their needs to improve their job competence. Although they were optimistic about pharmacovigilance and will not change their career, most of them were planning to change their employers. CONCLUSION: There was a gap between the demand and supply of pharmacovigilance personnel. Relevant regulatory authorities and industry associations should guide higher education institutions to collaborate with pharmacovigilance specialists to strengthen pharmacovigilance education for medical or pharmaceutical students, on the basis of which pharmacovigilance certification courses and continuing education courses can be developed. Meanwhile, pharmaceutical enterprises should consider reasonably adjusting work intensity and income to avoid a high turnover rate.

Characterisation and preliminary functional analysis of N-acetyltransferase 13 from Schistosoma japonicum.

BACKGROUND: N-acetyltransferase 13 (NAT13) is a probable catalytic component of the ARD1A-NARG1 complex possessing alpha (N-terminal) acetyltransferase activity. RESULTS: In this study, a full-length complementary DNA (cDNA) encoding Schistosoma japonicum NAT13 (SjNAT13) was isolated from schistosome cDNAs. The 621 bp open reading frame of SjNAT13 encodes a polypeptide of 206 amino acids. Real-time PCR analysis revealed SjNAT13 expression in all tested developmental stages. Transcript levels were highest in cercariae and 21-day-old worms, and higher in male adult worms than female adult worms. The rSjNAT13 protein induced high levels of anti-rSjNAT13 IgG antibodies. In two independent immunoprotection trials, rSjNAT13 induced 24.23% and 24.47% reductions in the numbers of eggs in liver. RNA interference (RNAi) results showed that small interfering RNA (siRNA) Sj-514 significantly reduced SjNAT13 transcript levels in worms and decreased egg production in vitro. CONCLUSIONS: Thus, rSjNAT13 might play an important role in the development and reproduction of schistosomes.

UPF1 association with the cap-binding protein, CBP80, promotes nonsense-mediated mRNA decay at two distinct steps.

Nonsense-mediated mRNA decay (NMD) is an mRNA surveillance mechanism that in mammals generally occurs upon recognition of a premature termination codon (PTC) during a pioneer round of translation. This round involves newly synthesized mRNA that is bound at its 5' end by the cap-binding protein (CBP) heterodimer CBP80-CBP20. Here we show that precluding the binding of the NMD factor UPF1 to CBP80 inhibits NMD at two steps: the association of SMG1 and UPF1 with the two eukaryotic release factors (eRFs) during SURF complex formation at a PTC, and the subsequent association of SMG1 and UPF1 with an exon-junction complex. We also demonstrate that UPF1 binds PTC-containing mRNA more efficiently than the corresponding PTC-free mRNA in a way that is promoted by the UPF1-CBP80 interaction. A unifying model proposes a choreographed series of protein-protein interactions occurring on an NMD target.

SMD and NMD are competitive pathways that contribute to myogenesis: effects on PAX3 and myogenin mRNAs.

UPF1 functions in both Staufen 1 (STAU1)-mediated mRNA decay (SMD) and nonsense-mediated mRNA decay (NMD), which we show here are competitive pathways. STAU1- and UPF2-binding sites within UPF1 overlap so that STAU1 and UPF2 binding to UPF1 appear to be mutually exclusive. Furthermore, down-regulating the cellular abundance of STAU1, which inhibits SMD, increases the efficiency of NMD, whereas down-regulating the cellular abundance of UPF2, which inhibits NMD, increases the efficiency of SMD. Competition under physiological conditions is exemplified during the differentiation of C2C12 myoblasts to myotubes: The efficiency of SMD increases and the efficiency of NMD decreases, consistent with our finding that more STAU1 but less UPF2 bind UPF1 in myotubes compared with myoblasts. Moreover, an increase in the cellular level of UPF3X during myogenesis results in an increase in the efficiency of an alternative NMD pathway that, unlike classical NMD, is largely insensitive to UPF2 down-regulation. We discuss the remarkable balance between SMD and the two types of NMD in view of data indicating that PAX3 mRNA is an SMD target whose decay promotes myogenesis whereas myogenin mRNA is a classical NMD target encoding a protein required for myogenesis.

Zilucoplan, a macrocyclic peptide inhibitor of human complement component 5, uses a dual mode of action to prevent terminal complement pathway activation.

Introduction: The complement system is a key component of the innate immune system, and its aberrant activation underlies the pathophysiology of various diseases. Zilucoplan is a macrocyclic peptide that binds and inhibits the cleavage/activation of human complement component 5 (C5). We present in vitro and ex vivo data on the mechanism of action of zilucoplan for the inhibition of C5 activation, including two clinically relevant C5 polymorphisms at R885. Methods: The interaction of zilucoplan with C5, including for clinical C5 R885 variants, was investigated using surface plasmon resonance (SPR), hemolysis assays, and ELISA. The interference of C5b6 formation by zilucoplan was investigated by native gel analysis and hemolysis assay. The permeability of zilucoplan in a reconstituted basement membrane was assessed by the partition of zilucoplan on Matrigel-coated transwell chambers. Results: Zilucoplan specifically bound human complement C5 with high affinity, competitively inhibited the binding of C5 to C3b, and blocked C5 cleavage by C5 convertases and the assembly of the cytolytic membrane attack complex (MAC, or C5b9). Zilucoplan fully prevented the in vitro activation of C5 clinical variants at R885 that have been previously reported to respond poorly to eculizumab treatment. Zilucoplan was further demonstrated to interfere with the formation of C5b6 and inhibit red blood cell (RBC) hemolysis induced by plasmin-mediated non-canonical C5 activation. Zilucoplan demonstrated greater permeability than a monoclonal C5 antibody in a reconstituted basement membrane model, providing a rationale for the rapid onset of action of zilucoplan observed in clinical studies. Conclusion: Our findings demonstrate that zilucoplan uses a dual mode of action to potently inhibit the activation of C5 and terminal complement pathway including wild-type and clinical R885 variants that do not respond to eculizumab treatment. These data may be relevant to the clinically demonstrated benefits of zilucoplan.

Corrigendum: Zilucoplan, a macrocyclic peptide inhibitor of human complement component 5, uses a dual mode of action to prevent terminal complement pathway activation.

[This corrects the article DOI: 10.3389/fimmu.2023.1213920.].

Diagnostic Efficacy of Plasma-Based Real-Time PCR for Schistosomiasis Japonica in Mice before and after Treatment with Praziquantel.

The prevalence of schistosomiasis japonica in China is now characterized by a low epidemic rate and low-intensity infections. Some diagnostic methods with high sensitivity and specificity are urgently needed to better monitor this disease in the current situation. In this study, the detection efficacy of a real-time fluorescent quantitative PCR (qPCR) assay was assessed for schistosomiasis japonica in mice, and before and after treatment with praziquantel (PZQ). Our results showed that the sensitivity of the qPCR was 99.3% (152/153, 95% CI: 96.41-99.98%) and its specificity was 100% (77/77, 95% CI: 95.32-100%) in mice infected with different numbers of Schistosoma japonicum. After the oral administration of PZQ, mice infected with 10 cercariae or 40 cercariae were all Schistosoma japonicum-negative 6 weeks after treatment. However, the negativity rates on a soluble egg antigen (SEA)-based enzyme-linked immunosorbent assay (ELISA) were only 34.8% (8/23, 10 cercariae group) and 6.7% (1/15, 40 cercariae group) at the sixth week after PZQ treatment. These results demonstrated that the qPCR method had good sensitivity and specificity, and suggested that its sensitivity correlated with the infection intensity in mice. Moreover, this method had better potential utility for evaluating the treatment efficacy of PZQ in schistosome-infected mice than SEA-based ELISA.

Prevention of Anti-HMGCR Immune-Mediated Necrotising Myopathy by C5 Complement Inhibition in a Humanised Mouse Model.

Introduction: immune-mediated necrotising myopathy (IMNM) is associated with pathogenic anti-signal recognition particle (SRP) or 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) antibodies, at least partly through activation of the classical pathway of the complement. We evaluated zilucoplan, an investigational drug, and a macrocyclic peptide inhibitor of complement component 5 (C5), in humanized mouse models of IMNM. Methods: purified immunoglobulin G (IgG) from an anti-HMGCR+ IMNM patient was co-injected intraperitoneally with human complement in C57BL/6, C5-deficient B10 (C5def) and Rag2 deficient (Rag2-/-) mice. Zilucoplan was administered subcutaneously in a preventive or interventional paradigm, either injected daily throughout the duration of the experiment in C57BL/6 and C5def mice or 8 days after disease induction in Rag2-/- mice. Results: prophylactic administration of zilucoplan prevented muscle strength loss in C5def mice (anti-HMGCR+ vs. anti-HMGCR+ + zilucoplan: p = 0.0289; control vs. anti-HMGCR+ + zilucoplan: p = 0.4634) and wild-type C57BL/6 (anti-HMGCR+ vs. anti-HMGCR+ + zilucoplan: p = 0.0002; control vs. anti-HMGCR+ + zilucoplan: p = 0.0939) with corresponding reduction in C5b-9 deposits on myofibres and number of regenerated myofibres. Interventional treatment of zilucoplan after disease induction reduced the complement deposits and number of regenerated myofibres in muscles of Rag2-/- mice, although to a lesser extent. In this latter setting, C5 inhibition did not significantly ameliorate muscle strength. Conclusion: Early administration of zilucoplan prevents the onset of myopathy at the clinical and histological level in a humanized mouse model of IMNM.

Human Neutrophils Respond to Complement Activation and Inhibition in Microfluidic Devices.

Complement activation is key to anti-microbial defenses by directly acting on microbes and indirectly by triggering cellular immune responses. Complement activation may also contribute to the pathogenesis of numerous inflammatory and immunological diseases. Consequently, intense research focuses on developing therapeutics that block pathology-causing complement activation while preserving anti-microbial complement activities. However, the pace of research is slowed down significantly by the limitations of current tools for evaluating complement-targeting therapeutics. Moreover, the effects of potential therapeutic agents on innate immune cells, like neutrophils, are not fully understood. Here, we employ microfluidic assays and measure chemotaxis, phagocytosis, and swarming changes in human neutrophils ex vivo in response to various complement-targeting agents. We show that whereas complement factor 5 (C5) cleavage inhibitor eculizumab blocks all neutrophil anti-microbial functions, newer compounds like the C5 cleavage inhibitor RA101295 and C5a receptor antagonist avacopan inhibit chemotaxis and swarming while preserving neutrophil phagocytosis. These results highlight the utility of microfluidic neutrophil assays in evaluating potential complement-targeting therapeutics.

Preoperative LMR and Serum CA125 Level as Risk Factors for Advanced Stage of Ovarian Cancer.

Objectives: This study was to analyze the relationships between lymphocyte-to-monocyte ratio (LMR) alone or combined with serum CA125 (COLC) and advanced stage of ovarian cancer (OC). Methods: The receiver-operating characteristic (ROC) curves of LMR, CA125, and COLC staging OC were constructed by a retrospective study. Furthermore, a binary logistic regression model was used to assay the independent risk factors for OC staging. Results: Two hundred and twenty-five patients with OC were identified in this cohort. Eighty-five OC patients were diagnosed at an early stage, and 140 OC patients were diagnosed at an advanced stage. The median of LMR in the early stage was higher than that in advanced stage (4.4 vs. 2.8), and the median of serum CA125 was lower than that in advanced stage (80 U/mL vs. 251.3 U/mL). Multivariate logistic regression LMR≤3.7 (OR=0.299, 95% CI: 0.093-0.962, P=0.043) and CA125>95.7 U/mL (OR=4.317, 95% CI: 1.436-12.977, P=0.009) were risk factors for stage of advanced OC whether presence or absence of malignant ascites. Furthermore, the area under the curve of COLC was higher than that of LMR (0.782 vs. 0.732) or serum CA125 (0.782 vs. 0.708) in staging OC. The specificity of COLC was higher than that of LMR (87.1% vs. 70.6%) or serum CA125 (87.1% vs. 61.2%) in staging OC. Conclusion: LMR alone or in combination with serum CA125 might be associated with OC staging. Besides, as a predictive factor, COLC may have a high specificity in staging OC.

The Chemical Synthesis of Knob Domain Antibody Fragments.

Cysteine-rich knob domains found in the ultralong complementarity determining regions of a subset of bovine antibodies are capable of functioning autonomously as 3-6 kDa peptides. While they can be expressed recombinantly in cellular systems, in this paper we show that knob domains are also readily amenable to a chemical synthesis, with a co-crystal structure of a chemically synthesized knob domain in complex with an antigen showing structural equivalence to the biological product. For drug discovery, following the immunization of cattle, knob domain peptides can be synthesized directly from antibody sequence data, combining the power and diversity of the bovine immune repertoire with the ability to rapidly incorporate nonbiological modifications. We demonstrate that, through rational design with non-natural amino acids, a paratope diversity can be massively expanded, in this case improving the efficacy of an allosteric peptide. As a potential route to further improve stability, we also performed head-to-tail cyclizations, exploiting the proximity of the N and C termini to synthesize functional, fully cyclic antibody fragments. Lastly, we highlight the stability of knob domains in plasma and, through pharmacokinetic studies, use palmitoylation as a route to extend the plasma half-life of knob domains in vivo. This study presents an antibody-derived medicinal chemistry platform, with protocols for solid-phase synthesis of knob domains, together with the characterization of their molecular structures, in vitro pharmacology, and pharmacokinetics.

Combined Preoperative LMR and CA125 for Prognostic Assessment of Ovarian Cancer.

Objectives: To investigate the role of inflammation-related factors, lymphocyte-to-monocyte ratio (LMR) alone and combined detection with cancer antigen 125 (CA125), in the prognostic assessment of ovarian cancer (OC). Methods: A retrospective clinicopathologic review was performed. The receiver-operating characteristic (ROC) curves of LMR, CA125, and COLC predicting mortality in OC patients were constructed. Besides, Kaplan-Meier and Cox logistic regression models were used to plot the survival curves and determine the independent prognostic factors. Results: A total of 214 OC patients were identified in this cohort. The mean duration of follow-up was 64 months (minimum 8 months, maximum 116 months). In this cohort, 135 cases died (63.1%), and the median progression-free survival (PFS) and overall survival (OS) were 20 and 39.5 months, respectively. Results of the multivariate Cox regression model showed that LMR≤3.8 (HR = 0.494, 95% CI: 0.329-0.742, P = 0.001) and CA125>34 U/ml (HR = 1.641, 95% CI: 1.057-2.550, P = 0.027) were significantly associated with poor PFS; and LMR≤3.8 (HR = 0.459, 95% CI: 0.306-0.688, P = <0.001) and CA125>34 U/ml (HR = 1.946, 95% CI: 1.256-3.015, P = 0.003) were significantly associated with OS. Furthermore, the area under the curve of COLC was higher (0.713) than that of LMR (0.709) or CA125 (0.583), the specificity of COLC was higher (75.9%) than that of LMR (62%) or CA125 (40.5%) in predicting mortality in OC patients. Conclusions: LMR alone and combined with CA125 might be used as predictive markers in OC. Furthermore, as a prognostic factor, COLC might have a higher specificity to predict the outcome.

Development of a Chitosan-based Nanoparticle Formulation for Ophthalmic Delivery of Honokiol.

BACKGROUND: Retinal neovascularization (NV) is the leading cause of blindness in the majority of ocular diseases. Several treatment approaches have been developed for retinal NV; of these methods, instillation of nanoparticles into the conjunctival sac has shown potential for retinal NV treatment because it does not cause physical damage and is easy to operate. METHODS: In this study, honokiol-loaded chitosan/sulfobutylether-ß-cyclodextrin nanoparticles (HKCS- NPs) were prepared for ophthalmic drug delivery systems. An inclusion complex of honokiol and sulfobutylether-ß-cyclodextrin was used to incorporated insoluble honokiol into chitosan nanoparticles, which were prepared through ionotropic gelation. RESULTS: HK-CS-NPs featured a spherical surface with a narrow size distribution of polydispersity index less than 0.250, a mean size range of 373-523 nm, a positive surface charge of +19.9 to +24.2 mV, and an entrapment efficiency of 84.92%. In vitro release studies showed an initial burst release phase and a sustained release phase of nanoparticles. Moreover, in vivo study showed that HK-CS-NPs exhibited good ocular tolerability and could improve ophthalmic bioavailability of honokiol. In particular, the maximum concentration of honokiol after administration of HK-CS-NPs was enhanced by 1.65 times compared with that after instillation of the honokiol suspension alone. CONCLUSION: This study proposes HK-CS-NPs as a potential ophthalmic delivery system.

High resistance of water buffalo against reinfection with Schistosoma japonicum.

Schistosomiasis is a zoonotic parasitic disease threatening tens of millions people and farm animals. Water buffalos are a major reservoir for schistosomiasis and a control target. Epidemiological surveys suggest that buffalos can develop resistance against Schistosoma japonicum reinfection. In the present paper, relative to control animals, we report an over 97% worm burden reduction after two rounds of infection with S. japonicum and treatment with Praziquantel (PZQ). Relative to control animals, shorter length of female worms, and lower egg counts (over 87.7% reduction rates) were observed in reinfected buffalos. We also found that the reinfected buffalos had significantly higher levels of IL-4, IL-10, and IFN-γ, 4-9 weeks after the secondary infection, and a significantly higher level of specific IgG antibodies before infection. Our results confirmed that after infection buffalos develop resistance against S. japonicum reinfection, and that this resistance is mainly due to acquired immunity. These findings may aid in the future vaccine design for water buffalos.

A Novel Microbubble Capable of Ultrasound-Triggered Release of Drug-Loaded Nanoparticles.

Drug-loaded microbubbles have shown attractive potential in disease treatment applications. The present work presents a unique ultrasound (US)-triggered system in which drug-loaded nanoparticles and perfluorocarbon gas are encapsulated within the internal space of microbubbles. The prepared curcumin-loaded albumin nanoparticle payload microbubbles (CcmANP-MB) exhibited a mean diameter of 4895.1 nm ± 421.2 nm and a drug-loading efficiency of 2.23% ± 0.08% (297% increase compared with the drug loading of common drug-loaded microbubbles). US allowed the release of the internal payload. In vitro US-triggered drug release experiments showed that the drug release of CcmANP-MB was delayed by lipid membranes and significantly increased after sonication. In vitro and in vivo US imaging experiments demonstrated that CcmANP-MB evidently enhances US imaging, which indicates that the microbubbles possess good acoustic properties even after encapsulation of nanoparticles. Tumor bearing mice were administered with CcmANP-MB through the tail vein and were then exposed to ultrasound, which resulted in an enhanced drug accumulation in tumor tissues and a significant increase in tumor growth inhibition rate (57.1%) compared with CcmANP-MB alone (28.8%) as well as curcumin-loaded albumin nanoparticle (26.2%). Therefore, the combination of lecithin microbubbles and albumin nanoparticles provides a platform for targeted drug delivery in clinical therapy and disease diagnosis.

Synthesis, characterization, and in vitro evaluation of curcumin-loaded albumin nanoparticles surface-functionalized with glycyrrhetinic acid.

We have designed and developed curcumin (Ccn)-loaded albumin nanoparticles (BNPs) surface-functionalized with glycyrrhetinic acid (Ccn-BNP-GA) for GA receptor-mediated targeting. Ccn-BNP-GA was prepared by conjugating GA as a hepatoma cell-specific binding molecule onto the surface of BNPs. Ccn-BNP-GA showed a narrow distribution with an average size of 258.8±6.4 nm, a regularly spherical shape, an entrapment efficiency of 88.55%±5.54%, and drug loading of 25.30%±1.58%. The density of GA as the ligand conjugated to BNPs was 140.48±2.784 µg/g bovine serum albumin. Cytotoxicity assay results indicated that Ccn-BNP-GA was significantly more cytotoxic to HepG2 cells and in a concentration-dependent manner. Ccn-BNP-GA also appeared to be taken up to a greater extent by HepG2 cells than undecorated groups, which might be due to the high affinity of GA for GA receptors on the HepG2 cell surface. These cytotoxicity assay results were corroborated by analysis of cell apoptosis and the cell cycle. Further, Ccn-BNP-GA showed an approximately twofold higher rate of cell apoptosis than the other groups. Moreover, proliferation of HepG2 cells was arrested in G2/M phase based on cell cycle analysis. These results, which were supported by the GA receptor-mediated endocytosis mechanism, indicate that BNPs surface-functionalized with GA could be used in targeted cancer treatment with high efficacy, sufficient targeting, and reduced toxicity.

Encapsulation of honokiol into self-assembled pectin nanoparticles for drug delivery to HepG2 cells.

Self-assembled pectin nanoparticles was prepared and evaluated for delivering the hydrophobic drug, honokiol (HK), to HepG2 cells. These hydrophobic drug-loaded nanoparticles were developed without using any surfactant and organic solvent. Hydroxypropyl-ß-cyclodextrin (HCD) was used to fabricate an inclusion complex with HK (HKHCD) to increase the solubility of the drug and thus facilitate its encapsulation and dispersion in the pectin nanoparticles. Investigation of the in vitro release indicated that the drug-loaded nanoparticles exhibited a higher drug release rate than free honokiol and an effective sustained-release. Cytotoxicity, cell apoptosis and cellular uptake studies further confirmed that the pectin nanoparticles with galactose residues generated higher cytotoxicity than free honokiol on HepG2 cells which highly expressed asialoglycoprotein receptors (ASGR). Nevertheless, these findings were not observed in ASGR-negative A549 cells under similar condition. Therefore, pectin nanoparticles demonstrated a specific active targeting ability to ASGR-positive HepG2 cells and could be used as a potential drug carrier for treatment of liver-related tumors.

[Effect of diet composition on expression of uncoupling protein-1 gene of rat].

In order to explore the effect of different diet composition on uncoupling proteins 1(UCP1) gene expression in brown adipose tissue, male Wistar rats are fed with different diets (basic diet, high protein diet, high fat diet, high calorie diet 1 and 2) for 2 months. The effects of different diets on weight and the ratio of fat mass to body weight are observed. Reverse transcription-polymerase chain reaction and western blotting technique are used to measure UCP1 mRNA and protein content of rat brown adipose tissue(BAT). The results show that body weight and the ratio of fat mass to body weight in high calorie 1 and 2 diet groups are obviously higher than those in groups of basic diet, high protein, and high fat diet (P < 0.05), but there is no significant difference among the last three groups (P > 0.05). UCP1 gene expression increases in both high calorie diet 1 group and 2 group, but it is not significantly different among basic diet, high protein and high fat diet groups with equal energy, indicating that energy can induce UCP1 gene expression of rat BAT.

Investigation of inclusion complex of honokiol with sulfobutyl ether-ß-cyclodextrin.

This study aimed to prepare and characterize an inclusion complex of honokiol (HNK) with sulfobutyl ether-ß-cyclodextrin (SB-ß-CD). The inclusion complex (HNK/CD COMP) was prepared utilizing a freeze-drying method. Phase-solubility curves were employed to obtain stability constants and thermodynamic parameters. The phase-solubility diagram showed a typical A(L)-type, indicating that the 1:1 (HNK:SB-ß-CD) inclusion complex was formed. The solid inclusion complex was then characterized by differential scanning calorimetry and Fourier transform infrared spectroscopy. Results showed that HNK/CD COMP exhibited a higher drug release rate than free HNK in vitro. A comparative study of the pharmacokinetics between HNK/CD COMP and free HNK was also performed in rats. In vivo results indicated that AUC0-t and Cmax of HNK/CD COMP increased by approximately 158% and 123% compared with those of the free HNK, respectively. These results suggest that SB-ß-CD will be potentially useful in the delivery of poorly soluble drugs, such as HNK.

mRNA-mRNA duplexes that autoelicit Staufen1-mediated mRNA decay.

We report a new mechanism by which human mRNAs cross-talk: an Alu element in the 3' untranslated region (3' UTR) of one mRNA can base-pair with a partially complementary Alu element in the 3' UTR of a different mRNA, thereby creating a Staufen1 (STAU1)-binding site (SBS). STAU1 binding to a 3'-UTR SBS was previously shown to trigger STAU1-mediated mRNA decay (SMD) by directly recruiting the ATP-dependent RNA helicase UPF1, which is also a key factor in the mechanistically related nonsense-mediated mRNA decay (NMD) pathway. In the case of a 3'-UTR SBS created by mRNA-mRNA base-pairing, we show that SMD targets both mRNAs in the duplex, provided that both mRNAs are translated. If only one mRNA is translated, then it alone is targeted for SMD. We demonstrate the functional importance of mRNA-mRNA-triggered SMD in cell migration and invasion.