Healthcare professionals' experiences of interprofessional collaboration in patient education: A systematic review.

OBJECTIVES: This study explores interprofessional collaboration amongst healthcare professionals in patient education. METHODS: A systematic review was conducted. A search in seven databases was conducted from 2011 to 2022 and screened against the inclusion criteria. Quality appraisal was done independently by two reviewers. Studies were extracted and synthesised using the data-based convergent synthesis design. RESULTS: Twenty-one studies were included. Five themes on factors affecting interprofessional collaboration in patient education emerged: 1) role clarification, 2) communication infrastructure, 3) shared space for collaboration, 4) interprofessional trust, and 5) organisational support. CONCLUSION: Findings highlighted the importance of developing trustful relationships within the multidisciplinary team in delivering patient education. Channels for additional infrastructural support, guidelines and training in patient education delivery is required. Future research could explore patients' perspectives on how their learning needs in patient education may be optimised through a multidisciplinary approach. PRACTICE IMPLICATIONS: Healthcare leaders could promote shared goals within the team by facilitating a common space and time for interprofessional team rounding, and by developing shared patient education resources and documentation processes. Interprofessional education focusing on the delivery of team-based patient education could be implemented to foster understanding of the interdependent role of multidisciplinary healthcare professionals.

Comprehensive Profiling of EBV Gene Expression and Promoter Methylation Reveals Latency II Viral Infection and Sporadic Abortive Lytic Activation in Peripheral T-Cell Lymphomas.

Epstein-Barr virus (EBV) latency patterns are well defined in EBV-associated epithelial, NK/T-cell, and B-cell malignancies, with links between latency stage and tumorigenesis deciphered in various studies. In vitro studies suggest that the oncogenic activity of EBV in T-cells might be somewhat different from that in EBV-tropic B lymphoid cells, prompting us to study this much less investigated viral gene expression pattern and its regulation in nine EBV+ peripheral T-cell lymphoma (PTCL) biopsies. Using frozen specimens, RT-PCR showed 6/7 cases with a latency II pattern of EBV gene expression. Analyses of EBNA1 promoter usage and CpG methylation status in these six cases showed that only Qp was used, while Cp, Wp, and Fp were all silent. However, the remaining case showed an exceptionally unique latency III type with lytic activation, as evidenced by EBV lytic clonality and confirmed by the full usage of Cp and Qp as well as weakly lytic Fp and Wp, fully unmethylated Cp and marginally unmethylated Wp. Further immunostaining of the eight cases revealed a few focally clustered LMP1+ cells in 7/8 cases, with rare isolated LMP1+ cells detected in another case. Double immunostaining confirmed that the LMP1+ cells were of the T-cell phenotype (CD3+). In 6/8 cases, sporadically scattered Zta+ cells were detected. Double staining of EBER-ISH with T-cell (CD45RO/UCHL1) or B-cell (CD20) markers confirmed that the vast majority of EBER+ cells were of the T-cell phenotype. Predominant type-A EBV variant and LMP1 30-bp deletion variant were present, with both F and f variants detected. In summary, the EBV gene expression pattern in PTCL was found to be mainly of latency II (BART+EBNA1(Qp)+LMP1+LMP2A+BZLF1+), similar to that previously reported in EBV-infected nasopharyngeal epithelial, NK/T-cell, and Hodgkin malignancies; however, fully lytic infection could also be detected in occasional cases. Rare cells with sporadic immediate-early gene expression were commonly detected in PTCL. These findings have implications for the future development of EBV-targeting therapeutics for this cancer.

Clinician by day, filmmaker by night: The development of a consumer inspired educational electroconvulsive therapy video.

OBJECTIVE: Electroconvulsive therapy (ECT) is a highly effective form of treatment used for major psychiatric disorders. However, significant stigma surrounds ECT and mental health consumers and they often report lack of knowledge prior to receiving ECT. They complain of inadequacies in information being provided by health professionals and difficulty finding reliable, balanced information that incorporates the experience of consumers who have received ECT. To address these limitations, a collaborative team of ECT consumers and health professionals created a new ECT video to provide consumers and their relatives with up-to-date, easy to understand information about ECT. The educational video includes evidence-based information from health professionals and genuine consumer perspectives. CONCLUSION: A gap in clinical care and service provision was identified and a collaborative project was undertaken to address these limitations. In the process of creating an ECT video, many lessons were learned and a range of recommendations were implemented, including a memory rehabilitation program and new and improved access to ECT information resources.

Effect of an Educational Video and Information Pamphlet on Knowledge and Attitudes About Electroconvulsive Therapy: A Randomized, Blind, Controlled Study.

OBJECTIVE: Electroconvulsive therapy (ECT) is considered an effective, yet underused and stigmatized form of psychiatric treatment. Public misconception can impact informed decision making, and therefore, it is important to educate the community with accurate and realistic representations of modern ECT. The aim of this study was to determine whether exposure to brief information packages developed in Australia leads to changes in attitudes and knowledge about ECT. METHODS: A sample of 100 undergraduate psychology students and 88 volunteers from the general public were randomly allocated to view 1 of 3 resource packages (each containing an information pamphlet and videos totaling ~15 minutes): Concord Centre for Mental Health-Revised, Concord Centre for Mental Health-Original, and a generic information package on depression. Participants' attitudes and knowledge of ECT were assessed before and after psychoeducation using the Questionnaire on Attitudes and Knowledge of ECT (QuAKE). RESULTS: Participants in the student and general population exposed to either ECT resource package showed significantly improved attitudes and knowledge of ECT compared with participants exposed to generic information about depression and its treatment. A fine-grained analysis of the QuAKE revealed that, although many aspects of knowledge and attitudes improved after exposure to ECT information packages, some remained unchanged. CONCLUSIONS: Brief education through information resources in video and written format can markedly improve attitudes and knowledge toward ECT. Further research is recommended to determine whether the resources contribute to informed decision making of consumers with mental illness, especially those who are candidates for ECT.

Aloin isoforms (A and B) selectively inhibits proteolytic and deubiquitinating activity of papain like protease (PLpro) of SARS-CoV-2 in vitro.

The most common host entry point of human adapted coronaviruses (CoV) including SARS-CoV-2 is through the initial colonization in the nostril and mouth region which is responsible for spread of the infection. Most recent studies suggest that the commercially available oral and nasal rinse products are effective in inhibiting the viral replication. However, the anti-viral mechanism of the active ingredients present in the oral rinses have not been studied. In the present study, we have assessed in vitro enzymatic inhibitory activity of active ingredients in the oral mouth rinse products: aloin A and B, chlorhexidine, eucalyptol, hexetidine, menthol, triclosan, methyl salicylate, sodium fluoride and povidone, against two important proteases of SARS-CoV-2 PLpro and 3CLpro. Our results indicate only aloin A and B effectively inhibited proteolytic activity of PLpro with an IC50 of 13.16 and 16.08 µM. Interestingly, neither of the aloin isoforms inhibited 3CLpro enzymatic activity. Computational structural modelling of aloin A and B interaction with PLpro revealed that, both aloin isoforms form hydrogen bond with Tyr268 of PLpro, which is critical for their proteolytic activity. Furthermore, 100 ns molecular dynamics (MD) simulation studies predicted that both aloin isoforms have strong interaction with Glu167, which is required for PLpro deubiquitination activity. Our results from the in vitro deubiquitinase inhibition assay show that aloin A and B isomers exhibit deubiquitination inhibitory activity with an IC50 value of 15.68 and 17.51 µM, respectively. In conclusion, the isoforms of aloin inhibit both proteolytic and the deubiquitinating activity of SARS-CoV-2 PLpro, suggesting potential in inhibiting the replication of SARS-CoV-2 virus.

Identification of 3-chymotrypsin like protease (3CLPro) inhibitors as potential anti-SARS-CoV-2 agents.

Emerging outbreak of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection is a major threat to public health. The morbidity is increasing due to lack of SARS-CoV-2 specific drugs. Herein, we have identified potential drugs that target the 3-chymotrypsin like protease (3CLpro), the main protease that is pivotal for the replication of SARS-CoV-2. Computational molecular modeling was used to screen 3987 FDA approved drugs, and 47 drugs were selected to study their inhibitory effects on SARS-CoV-2 specific 3CLpro enzyme in vitro. Our results indicate that boceprevir, ombitasvir, paritaprevir, tipranavir, ivermectin, and micafungin exhibited inhibitory effect towards 3CLpro enzymatic activity. The 100 ns molecular dynamics simulation studies showed that ivermectin may require homodimeric form of 3CLpro enzyme for its inhibitory activity. In summary, these molecules could be useful to develop highly specific therapeutically viable drugs to inhibit the SARS-CoV-2 replication either alone or in combination with drugs specific for other SARS-CoV-2 viral targets.

Randomized, placebo-controlled, double-blind, pilot trial to investigate safety and efficacy of Cerebrolysin in patients with aneurysmal subarachnoid hemorrhage.

ASBTRACT: BACKGROUND: There are limited neuroprotective treatment options for patients with aneurysmal subarachnoid hemorrhage (SAH). Cerebrolysin, a brain-specific proposed pleiotropic neuroprotective agent, has been suggested to improve global functional outcomes in ischemic stroke. We investigated the efficacy, safety and feasibility of administering Cerebrolysin for SAH patients. METHODS: This was a prospective, randomized, double-blind, placebo-controlled, single-center, parallel-group pilot study. Fifty patients received either daily Cerebrolysin (30 ml/day) or a placebo (saline) for 14 days (25 patients per study group). The primary endpoint was a favorable Extended Glasgow Outcome Scale (GOSE) of 5 to 8 (moderate disability to good recovery) at six-months. Secondary endpoints included the modified Ranking Scale (mRS), the Montreal Cognitive Assessment (MOCA) score, occurrence of adverse effects and the occurrence of delayed cerebral ischemia (DCI). RESULTS: No severe adverse effects or mortality attributable to Cerebrolysin were observed. No significant difference was detected in the proportion of patients with favorable six-month GOSE in either study group (odds ratio (OR): 1.49; 95% confidence interval (CI): 0.43-5.17). Secondary functional outcome measures for favorable six-month recovery i.e. a mRS of 0 to 3 (OR: 3.45; 95% CI 0.79-15.01) were comparable for both groups. Similarly, there was no difference in MOCA neurocognitive performance (p-value: 0.75) and in the incidence of DCI (OR: 0.85 95% CI: 0.28-2.59). CONCLUSIONS: Use of Cerebrolysin in addition to standard-of-care management of aneurysmal SAH is safe, well tolerated and feasible. However, the neutral results of this trial suggest that it does not improve the six-month global functional performance of patients. CLINICAL TRIAL REGISTRATION: Name of Registry: ClinicalTrials.gov Trial Registration Number: NCT01787123 . Date of Registration: 8th February 2013.

Lipocalin-2 deficiency may predispose to the progression of spontaneous age-related adiposity in mice.

Lipocalin-2 (Lcn2) is an innate immune protein elevated by several orders of magnitude in various inflammatory conditions including aging and obesity. Recent studies have shown that Lcn2 is secreted by adipocytes in response to inflammation and is categorized as a new adipokine cross-linking innate immunity and metabolic disorders including obesity. However, the involvement of Lcn2 and its function during the progression of obesity is largely unknown. Recently, browning of white adipose tissue (WAT) has gained attention as a therapeutic strategy to combat obesity. Herein, we have shown that treatment of mature 3T3-L1 adipocytes with recombinant Lcn2 (rec-Lcn2) resulted in the up-regulation of thermogenic and beige/brown markers (UCP1, PRDM16, ZIC-1 and TBX1) and increased mitochondrial activity. Additionally, global Lcn2 genetic knockout (Lcn2KO) mice exhibited accelerated weight gain and visceral fat deposition with age, when compared to wild type (WT) mice. Taken together, both in vitro and in vivo studies suggest that Lcn2 is a naturally occurring adipokine, and may serve as an anti-obesity agent by upregulating the thermogenic markers resulting in the browning of WAT. Therefore, Lcn2 and its downstream signaling pathways could be a potential therapeutic target for obesity.

Incidence, Presentation, and Risk Factors for Sodium Valproate-Associated Hyperammonemia in Neurosurgical Patients: A Prospective, Observational Study.

OBJECTIVE: Sodium valproate (VPA) is a commonly prescribed antiepileptic drug (AED) in daily neurosurgical practice. However, the incidence of VPA-associated hyperammonemia (VAH) and its life-threatening consequence, VPA-induced hyperammonemic encephalopathy (VHE), in neurosurgical patients is unknown. We determined the incidence, clinical presentation, and risk factors for VAH. METHODS: This prospective cohort study was performed on adult neurosurgical patients prescribed VPA for at least a week over a 22-month period. Blood tests for ammonia, VPA, and liver function were performed at the time of recruitment. The primary end point was VAH. Secondary end points were VHE and liver dysfunction. RESULTS: In total, 252 patients were recruited. The commonest disease etiology was brain tumors (27%, 69), followed by aneurysmal subarachnoid hemorrhage (SAH; 26%, 65). VPA was prescribed for primary seizure prophylaxis in 110 patients (44%). The mean daily dose was 1148 mg for a mean duration of 48 months. The mean serum VPA level was 417 µmol/L. In total, 92 patients (37%) were prescribed an additional AED, the most common being phenytoin (65%, 60/92). The mean serum ammonia level was 47 µmol/L. In total, 28% (71/252) of patients had VAH and only 0.7% had VHE. Independent factors were aneurysmal SAH (adjusted odds ratio [aOR] 2.1; 95% confidence interval [CI] 1.1-4.2), concomitant phenytoin (aOR 1.9; 95% CI 1.0-3.5), and phenobarbital (aOR 4.6; 95% CI 1.1-20.0). No associations with VPA dose, duration, serum levels, and liver function were observed. CONCLUSIONS: Although VAH is common among neurosurgical patients, VHE is rare. Patients with aneurysmal SAH or on concomitant enzyme-inducing AEDs are at risk. Clinicians should be vigilant for VHE symptoms in these patients.

A rare cause of sciatica discovered during digital rectal examination: case report of an intrapelvic sciatic notch schwannoma.

Intrapelvic sciatic nerve schwannomas are rare causes for non-discogenic sciatica. We describe a 44-year-old female who had a palpable mass on digital rectal examination that exhibited a positive Tinel's sign. The schwannoma was excised by a posterior transgluteal approach. Patients with negative spinal imaging should undergo pelvic scanning to rule out these tumors.

Decision making and support available to individuals considering and undertaking electroconvulsive therapy (ECT): a qualitative, consumer-led study.

BACKGROUND: Electroconvulsive therapy (ECT) is one of the most controversial treatments in psychiatry. This controversy and diverse and often strongly held opinions can make decision making processes around ECT more complex. METHOD: This consumer-led project explored the experiences of individuals who had received ECT in terms of the information they received, their experience of ECT and suggestions for ways that decision making processes and experiences of ECT can be improved. Interviews were conducted by consumer researchers who had also received ECT and transcripts were analysed using constant comparative techniques. RESULTS: Seventeen individuals participated. Four overarching categories were identified from participant interviews: Information matters; Preparation and decisions before ECT; Experience of ECT; and Suggestions for improvement. Most participants suggested that more information was required and that this information should be made available more regularly to support decision making. Additional suggestions included greater involvement of family and friends (including having a family member or friend present during the ECT procedure), opportunities to gain information from individuals who had received ECT and more support for managing memory and cognitive side effects. CONCLUSION: This study provides valuable consumer-provided insights and recommendations for psychiatrists and mental health clinicians working within ECT clinics and with consumers considering or preparing for ECT.

Intra-arterial revascularization therapy for basilar artery occlusion-a systematic review and analysis.

Acute basilar artery occlusion has been managed aggressively with various modalities due to its potentially debilitating outcome. While intra-arterial mechanical thrombectomy with stentriever has established clear evidence for anterior circulation stroke with large vessel occlusion as an adjunct to intravenous thrombolysis or the sole modality in intravenous thrombolysis ineligible patients, similar high-level evidence was not available for intra-arterial mechanical thrombectomy of posterior circulation stroke with acute basilar artery occlusion. We hence perform a systematic review of current literature to compare intra-arterial pharmacological thrombolysis (IA-P) and intra-arterial mechanical thrombectomy (IA-MT) for acute basilar artery occlusion. Forty-one studies published between 1996 and 2015 were compared and studied by odds ratio analysis using Mantel-Haenszel risk ratio estimation, and time trend analysis using meta-regression. Patients in the IA-MT group were older, presented with more severe stroke, and more likely received treatment more than 12 h since onset of stroke. At 3 months, survival and clinical outcome were superior in the IA-MT group than the IA-P group, associated with higher recanalization rate. There were no difference between proportion of dependent survivors, and rate of symptomatic intracerebral hemorrhage across groups. Intra-arterial thrombolysis with mechanical devices led to improved survival, better short-term clinical outcome and higher recanalization rate than intra-arterial pharmacological thrombolysis.

Downregulation of the gli transcription factors regulator Kif7 facilitates cell survival and migration of choriocarcinoma cells.

The kinesin protein Kif7 has been recognized as an integral component of hedgehog signalling. Aberrant activation of hedgehog signalling has been implicated in many human solid tumours. Gestational trophoblastic disease includes frankly malignant choriocarcinoma and potentially malignant hydatidiform mole. Here we investigated the hedgehog signalling components expression profiles in gestational trophoblastic disease. Downregulation of Gli1, Gli2, Gli3 and Kif7 was demonstrated in clinical samples of choriocarcinoma and hydatidiform moles as well as choriocarcinoma cell lines when compared with normal placentas. Ectopic expression of Kif7 in two choriocarcinoma cell lines JAR and JEG-3 led to a decrease in cell growth and increase in apoptosis demonstrated by MTT and TUNEL assays, respectively. Overexpression of Kif7 also led to suppressed cell migration through transwell assay. In contrast, knocking down Kif7 in HTR-8/SVneo, an immortalized trophoblast cell line, increased cell number over time and increased the migratory ability of the cells. Taken together, Kif7 may contribute to pathogenesis of gestational trophoblastic disease through enhancing survival and promoting dissemination of trophoblasts.

IL-15 and macrophage secretory factors facilitate immune activation of neonatal natural killer cells by lipoteichoic acid.

Neonates possess a relatively "naive", yet inducible immune system. Our hypothesis is that upon strategic antigen exposure, cytokine priming and sensitization by accessory cells, natural killer (NK) cells could be activated to become a functional phenotype. We investigated the in vitro stimulation of cord blood (CB) and adult NK cells upon challenge with lipoteichoic acid (LTA), interleukin (IL)-15 and LTA-primed autologous macrophage-conditioned medium, using CD107a and CD69 phenotypes as indicators of activation. We also examined response of CB macrophages to LTA, in terms of P44/42 extracellular signal-regulated kinases (ERK1/2) activation and cytokine secretion. LTA significantly induced secretion of inflammatory cytokines tumor necrotic factor (TNF)-α, IL-6, IL-12 and activated the upstream signal of ERK1/2 phosphorylation in neonatal macrophages. The magnitude of responses to stimulation differed between neonatal and adult NK cells. Co-stimulation with IL-15 was critical for expansion of the CD69 and CD107a NK subpopulations in both neonatal and adult cells, upon a LTA challenge. NK cell activation could be enhanced by LTA-primed autologous macrophages through secretory factors. Our results indicated that neonatal macrophages and NK cells can evoke immunologic responses to a Gram-positive bacterial antigen. The combinatory priming strategy is relevant for development of novel protocols, such as IL-15 treatment, to compensate for the immaturity of the innate immune system in newborns against bacterial infections.

Rehabilitation of everyday memory deficits in paediatric brain injury: self-instruction and diary training.

Memory problems that interfere with everyday living are frequently reported in children who have sustained acquired brain injury (ABI), but their nature and rehabilitation is under-researched. This study aimed to (1) determine neuropsychological correlates of everyday memory deficits in children with ABI, and (2) investigate the effectiveness of a newly developed programme for their rehabilitation. We assessed everyday memory, verbal memory, attention and behaviour in 15 children with ABI. The children attended the everyday memory rehabilitation programme: six weekly sessions that involved diary training, self-instruction training and case examples. At the onset we found that everyday memory problems were related to impaired attention and behavioural difficulties. On completion of the programme there was a significant increase in children's abilities to perform daily routines that demanded recall of information and events. In addition, children used diaries more frequently. Moreover, significant secondary gains were found in attention and mood (anxiety and depression). In conclusion, the results provided preliminary evidence that our six week programme could be effective in reducing everyday memory difficulties and improving psychological well-being in children with ABI.

p21-Activated kinase-1 promotes aggressive phenotype, cell proliferation, and invasion in gestational trophoblastic disease.

Gestational trophoblastic disease (GTD) includes hydatidiform mole (HM), which can develop persistent gestational trophoblastic neoplasia requiring chemotherapy; choriocarcinoma, which is a frankly malignant tumor; placental site trophoblastic tumor; and epithelioid trophoblastic tumor. p21-Activated kinases (PAKs) promote malignant tumor progression. Therefore, this study investigated PAK1, PAK2, and p-PAK2 Ser(20) in the pathogenesis of GTD. By real-time PCR, PAK1 mRNA was significantly higher in HMs, particularly metastatic HMs (P = 0.046) and HMs that developed persistent disease (P = 0.011), when compared with normal placentas. By immunohistochemistry, significantly increased cytoplasmic PAK1 immunoreactivity in cytotrophoblasts was also detected in HMs (P = 0.042) and choriocarcinomas (P = 0.003). In addition, HMs that developed persistent disease displayed higher PAK1 immunoreactivity than those that regressed (P = 0.016), and elevated PAK1 immunoreactivity was observed in placental site trophoblastic tumors. Indeed, there was significant positive correlation between PAK1 expression and the proliferative indices Ki-67 (P = 0.016) and MCM7 (P = 0.026). Moreover, higher PAK1 mRNA and protein expression was confirmed in the choriocarcinoma cell-lines JEG-3 and JAR; however, PAK2 mRNA and p-PAK2 immunoreactivity showed a similar expression pattern in normal first trimester placentas and GTD. Knockdown of PAK1 in JEG-3 and JAR reduced cell proliferation, migration, and invasion ability, up-regulated p16, and down-regulated vascular endothelial growth factor and MT1-MMP expression. This is the first report revealing the involvement of PAK1 in the pathogenesis and clinical progress of GTD.

Reliability and validity of the Euthanasia Attitude Scale (EAS) for Hong Kong medical doctors.

This study aimed to examine the reliability and validity of the Euthanasia Attitude Scale (EAS) in Hong Kong medical doctors. A total of 107 medical doctors (61.7% men) participated in a survey at clinical settings in 2008. The 21-item EAS was used to assess their attitudes toward euthanasia. The mean (standard deviation) and median of the EAS were 63.60 (60.31) and 63.00. Total EAS scores correlated well with ''Ethical Considerations,'' ''Practical Considerations,'' and ''Treasuring Life'' (Spearman rho =.37-.96, P < .001) but not ''Naturalistic Beliefs.'' The construct validity of the 3-factor model was appropriate (Kaiser-Meyer-Olkin [KMO] value = 0.90) and showed high internal consistency (Cronbach alpha =.79-.92). Euthanasia Attitude Scale may be a reliable and valid measure for assessing the attitudes toward euthanasia in medical professionals.

NKp44 receptor mediates interaction of the envelope glycoproteins from the West Nile and dengue viruses with NK cells.

Dengue virus (DV) and West Nile virus (WNV) have become a global concern due to their widespread distribution and their ability to cause a variety of human diseases. Antiviral immune defenses involve NK cells. In the present study, we investigated the interaction between NK cells and these two flaviviruses. We show that the NK-activating receptor NKp44 is involved in virally mediated NK activation through direct interaction with the flavivirus envelope protein. Recombinant NKp44 directly binds to purified DV and WNV envelope proteins and specifically to domain III of WNV envelope protein; it also binds to WNV virus-like particles. These WNV-virus-like particles and WNV-domain III of WNV envelope protein directly bind NK cells expressing high levels of NKp44. Functionally, interaction of NK cells with infective and inactivated WNV results in NKp44-mediated NK degranulation. Finally, WNV infection of cells results in increased binding of rNKp44 that is specifically inhibited by anti-WNV serum. WNV-infected target cells induce IFN-gamma secretion and augmented lysis by NKp44-expressing primary NK cells that are blocked by anti-NKp44 Abs. Our findings show that triggering of NK cells by flavivirus is mediated by interaction of NKp44 with the flavivirus envelope protein.

Proline-rich tyrosine kinase 2 (Pyk2) promotes proliferation and invasiveness of hepatocellular carcinoma cells through c-Src/ERK activation.

The aim of the current study is to elucidate the mechanism of proline-rich tyrosine kinase 2 (Pyk2)-mediated cell proliferation and invasiveness in hepatocellular carcinoma (HCC) cells. Human HCC cell lines PLC and MHCC97L were stably transfected with either full-length Pyk2 or C-terminal non-kinase region of Pyk2 (PRNK). Functional studies on cell proliferation and invasion were conducted in vitro by colony formation assay, adhesion assay, migration assay and wound-healing assay. For the in vivo study, an orthotopic nude mice liver tumor model was applied to investigate the effects of Pyk2 overexpression on tumor growth and metastasis. Overexpression of Pyk2 in PLC cells resulted in an upregulation of colony formation (P = 0.021) and adhesion toward laminin (P = 0.018). Pyk2 promoted wound recovery by stimulation of actin stress fiber polymerization. In the in vivo study, transfection of PRNK in MHCC97L cells significantly decreased tumor volume (P = 0.001) and the incidence of lung metastasis (P = 0.014). Overexpression of Pyk2 promoted the activation of c-Src, formation of Pyk2/c-Src complex and activated the extracellular signal-regulated kinase (ERK)/mitogen-activated protein kinase (MAPK)-signaling pathway. Pyk2 upregulated the activation of ERK1/2 that is insensitive to MAPK/ERK kinase (MEK)1/2 inhibition. On the contrary, PRNK overexpression downregulated the activation of c-Src and ERK/MAPK-signaling pathways. Immunofluorescence staining showed that the focal adhesion localization of Pyk2 is a major determinant for c-Src and ERK/MAPK activation. In conclusion, our results showed that Pyk2 promoted cell proliferation and invasiveness by upregulation of the c-Src and ERK/MAPK-signaling pathways.

H5-type influenza virus hemagglutinin is functionally recognized by the natural killer-activating receptor NKp44.

Antiviral immune defenses involve natural killer (NK) cells. We previously showed that the NK-activating receptor NKp44 is involved in the functional recognition of H1-type influenza virus strains by NK cells. In the present study, we investigated the interaction of NKp44 and the hemagglutinin of a primary influenza virus H5N1 isolate. Here we show that recombinant NKp44 recognizes H5-expressing cells and specifically interacts with soluble H5 hemagglutinin. H5-pseudotyped lentiviral particles bind to NK cells expressing NKp44. Following interaction with target cells expressing H5, pseudotyped lentiviral particles, or membrane-associated H5, NK cells show NKp44-mediated induced activity. These findings indicate that NKp44-H5 interactions induce functional NK activation.