Anti-Apoptotic Effects of SERPIN B3 and B4 via STAT6 Activation in Macrophages after Infection with Toxoplasma gondii

Toxoplasma gondii penetrates all kinds of nucleated eukaryotic cells but modulates host cells differently for its intracellular survival. In a previous study, we found out that serine protease inhibitors B3 and B4 (SERPIN B3/B4 because of their very high homology) were significantly induced in THP-1-derived macrophages infected with T. gondii through activation of STAT6. In this study, to evaluate the effects of the induced SERPIN B3/B4 on the apoptosis of T. gondii-infected THP-1 cells, we designed and tested various small interfering (si-) RNAs of SERPIN B3 or B4 in staurosporine-induced apoptosis of THP-1 cells. Anti-apoptotic characteristics of THP-1 cells after infection with T. gondii disappeared when SERPIN B3/B4 were knock-downed with gene specific si-RNAs transfected into THP-1 cells as detected by the cleaved caspase 3, poly-ADP ribose polymerase and DNA fragmentation. This anti-apoptotic effect was confirmed in SERPIN B3/B4 overexpressed HeLa cells. We also investigated whether inhibition of STAT6 affects the function of SERPIN B3/B4, and vice versa. Inhibition of SERPIN B3/B4 did not influence STAT6 expression but SERPIN B3/B4 expression was inhibited by STAT6 si-RNA transfection, which confirmed that SERPIN B3/B4 was induced under the control of STAT6 activation. These results suggest that T. gondii induces SERPIN B3/B4 expression via STAT6 activation to inhibit the apoptosis of infected THP-1 cells for longer survival of the intracellular parasites themselves

Effects of uncertainty and spousal support on infertility-related quality of life in women undergoing assisted reproductive technologies

Purpose The purpose of this study was to investigate the effects of uncertainty and spousal support on infertility-related quality of life (QoL) in women undergoing assisted reproductive technologies. Methods In this correlational survey study, 172 infertile women undergoing assisted reproductive technologies for infertility treatment at M hospital in Seoul participated. Data collection took place at the outpatient department of M hospital using a self-report questionnaire from July to August 2019. Data were analyzed using SPSS for Windows version 28.0. Results The mean scores for uncertainty, spousal support, and infertility-related quality of life (QoL) were 28.35 (out of 50), 86.67 (out of 115), and 57.98 (out of 100), respectively. Infertility-related quality of life (QoL) was positively correlated with spousal support and negatively correlated with uncertainty. According to the regression analysis, infertility-related quality of life (QoL) was significantly affected by uncertainty, total number of assisted reproductive technology treatments, marriage duration, subjective health status, the financial burden of infertility testing, and the presence of a burdensome person. These variables had an explanatory power of 35.0% for infertility-related quality of life (QoL). Conclusion Uncertainty was an important factor influencing infertility-related quality of life (QoL) among women undergoing assisted reproductive technologies. It is necessary to develop and implement a nursing intervention program focused on reducing various forms of uncertainty during assisted reproductive procedures and to consider other factors affecting infertility-related quality of life (QoL) in the clinical setting

Effects of stress, depression, and spousal and familial support on maternal identity in pregnant women

Purpose The objective of this study was to identify the factors influencing maternal identity in pregnant women. Methods Using a descriptive research design, a cross-sectional survey was conducted. In total, 127 pregnant women were recruited from a tertiary hospital in Korea from January to April 2019. Measurements included maternal identity, stress, depression, spousal and familial support, and demographic and obstetric characteristics. Data were analyzed by descriptive statistics, the independent t-test, one-way ANOVA, Pearson correlation coefficients, and stepwise multiple regression using SPSS version 25.0. Results The mean score for maternal identity was 131.15 out of 160, and the mean scores for stress, depression, and spousal and familial support were 14.59 (out of 40), 6.82 (out of 30), and 109.04 (out of 132), respectively. Stress (r=–.38, p<.001), depression (r=–.37, p<.001), and spousal and familial support (r=.37, p<.001) were significantly correlated with maternal identity. In multiple regression analysis, stress (β=–0.27, p=.005) and spousal and familial support (β=0.23, p=.014) were found to be significant factors influencing maternal identity in pregnant women (F=14.19, p<.001). Conclusion It is necessary to develop effective strategies to mitigate stress and to encourage spousal and familial support in pregnant women. Such strategies could further enable pregnant women to enhance their maternal identity

Homeobox gene Dlx-2 is implicated in metabolic stress-induced necrosis

<p>Abstract</p> <p>Background</p> <p>In contrast to tumor-suppressive apoptosis and autophagic cell death, necrosis promotes tumor progression by releasing the pro-inflammatory and tumor-promoting cytokine high mobility group box 1 (HMGB1), and its presence in tumor patients is associated with poor prognosis. Thus, necrosis has important clinical implications in tumor development; however, its molecular mechanism remains poorly understood.</p> <p>Results</p> <p>In the present study, we show that Distal-less 2 (Dlx-2), a homeobox gene of the Dlx family that is involved in embryonic development, is induced in cancer cell lines dependently of reactive oxygen species (ROS) in response to glucose deprivation (GD), one of the metabolic stresses occurring in solid tumors. Increased Dlx-2 expression was also detected in the inner regions, which experience metabolic stress, of human tumors and of a multicellular tumor spheroid, an <it>in vitro </it>model of solid tumors. Dlx-2 short hairpin RNA (shRNA) inhibited metabolic stress-induced increase in propidium iodide-positive cell population and HMGB1 and lactate dehydrogenase (LDH) release, indicating the important role(s) of Dlx-2 in metabolic stress-induced necrosis. Dlx-2 shRNA appeared to exert its anti-necrotic effects by preventing metabolic stress-induced increases in mitochondrial ROS, which are responsible for triggering necrosis.</p> <p>Conclusions</p> <p>These results suggest that Dlx-2 may be involved in tumor progression via the regulation of metabolic stress-induced necrosis.</p

JNK pathway is involved in the inhibition of inflammatory target gene expression and NF-kappaB activation by melittin

<p>Abstract</p> <p>Background</p> <p>Bee venom therapy has been used to treat inflammatory diseases including rheumatoid arthritis in humans and in experimental animals. We previously found that bee venom and melittin (a major component of bee venom) have anti-inflammatory effect by reacting with the sulfhydryl group of p50 of nuclear factor-kappa B (NF-κB) and IκB kinases (IKKs). Since mitogen activated protein (MAP) kinase family is implicated in the NF-κB activation and inflammatory reaction, we further investigated whether activation of MAP kinase may be also involved in the anti-inflammatory effect of melittin and bee venom.</p> <p>Methods</p> <p>The anti-inflammatory effects of melittin and bee venom were investigated in cultured Raw 264.7 cells, THP-1 human monocytic cells and Synoviocytes. The activation of NF-κB was investigated by electrophoretic mobility shift assay. Nitric oxide (NO) and prostaglandin E₂(PGE₂) were determined either by Enzyme Linked Immuno Sorbent Assay or by biochemical assay. Expression of IκB, p50, p65, inducible nitric oxide synthetase (iNOS), cyclooxygenase-2 (COX-2) as well as phosphorylation of MAP kinase family was determined by Western blot.</p> <p>Results</p> <p>Melittin (0.5–5 μg/ml) and bee venom (5 and 10 μg/ml) inhibited lipopolysaccharide (LPS, 1 μg/ml) and sodium nitroprusside (SNP, 200 μM)-induced activation of c-Jun NH2-terminal kinase (JNK) in RAW 264.7 cells in a dose dependent manner. However, JNK inhibitor, anthra [1,9-cd]pyrazole-6 (2H)-one (SP600215, 10–50 μM) dose dependently suppressed the inhibitory effects of melittin and bee venom on NF-κB dependent luciferase and DNA binding activity via suppression of the inhibitory effect of melittin and bee venom on the LPS and SNP-induced translocation of p65 and p50 into nucleus as well as cytosolic release of IκB. Moreover, JNK inhibitor suppressed the inhibitory effects of melittin and bee venom on iNOS and COX-2 expression, and on NO and PGE₂generation.</p> <p>Conclusion</p> <p>These data show that melittin and bee venom prevent LPS and SNP-induced NO and PGE₂production via JNK pathway dependent inactivation of NF-κB, and suggest that inactivation of JNK pathways may also contribute to the anti-inflammatory and anti-arthritis effects of melittin and bee venom.</p

Does a nurse-led postpartum self-care program for first-time mothers in Bangladesh improve postpartum fatigue, depressive mood, and maternal functioning?: a non-synchronized quasi-experimental study

Purpose This study aimed to test the efficacy of a nurse-led postpartum self-care (NLPPSC) intervention at reducing postpartum fatigue (PPF) and depressive mood and promoting maternal functioning among first-time mothers in Bangladesh. Methods A non-synchronized quasi-experimental design was used. First-time mothers were recruited during postpartum and assigned to the experimental or control group (34 each). The experimental group received the NLPPSC in the hospital, a 1-day intervention that focused on increasing self-efficacy. The control group received usual care. Data on PPF, depressive mood, maternal functioning, self-care behaviors, postpartum self-efficacy, and self-care knowledge were collected at postpartum 2 weeks (attrition 23.5%) and 6 weeks (attrition 16.1%). Data were analyzed using descriptive statistics, bivariate statistics, and linear mixed model analysis. Results One-third (33.3%) of new mothers experienced depressive mood (Edinburgh Postnatal Depression Scale scores of ≥13 points). The NLPPSC intervention was statistically significant in decreasing PPF (β=–6.17, SE=1.81, t=–3.39, p<.01) and increased maternal functioning at postpartum 6 weeks in the experimental group (β=13.72, t=3.73, p<.01) compared to the control. Knowledge was also statistically significant for increased maternal functioning over time (β=.37, SE=.18, t=2.03, p<.05). However, there were no statistically significant differences in depressive mood over time. Conclusion The NLPPSC intervention was feasible and effective in improving fatigue and maternal functioning in Bangladeshi mothers by postpartum 6 weeks. Postpartum care knowledge was effective in improved maternal functioning and thus supports implementing the NLPPSC intervention for new mothers after childbirth

Clinical MetaData ontology: a simple classification scheme for data elements of clinical data based on semantics

Background The increasing use of common data elements (CDEs) in numerous research projects and clinical applications has made it imperative to create an effective classification scheme for the efficient management of these data elements. We applied high-level integrative modeling of entire clinical documents from real-world practice to create the Clinical MetaData Ontology (CMDO) for the appropriate classification and integration of CDEs that are in practical use in current clinical documents. Methods CMDO was developed using the General Formal Ontology method with a manual iterative process comprising five steps: (1) defining the scope of CMDO by conceptualizing its first-level terms based on an analysis of clinical-practice procedures, (2) identifying CMDO concepts for representing clinical data of general CDEs by examining how and what clinical data are generated with flows of clinical care practices, (3) assigning hierarchical relationships for CMDO concepts, (4) developing CMDO properties (e.g., synonyms, preferred terms, and definitions) for each CMDO concept, and (5) evaluating the utility of CMDO. Results We created CMDO comprising 189 concepts under the 4 first-level classes of Description, Event, Finding, and Procedure. CMDO has 256 definitions that cover the 189 CMDO concepts, with 459 synonyms for 139 (74.0%) of the concepts. All of the CDEs extracted from 6 HL7 templates, 25 clinical documents of 5 teaching hospitals, and 1 personal health record specification were successfully annotated by 41 (21.9%), 89 (47.6%), and 13 (7.0%) of the CMDO concepts, respectively. We created a CMDO Browser to facilitate navigation of the CMDO concept hierarchy and a CMDO-enabled CDE Browser for displaying the relationships between CMDO concepts and the CDEs extracted from the clinical documents that are used in current practice. Conclusions CMDO is an ontology and classification scheme for CDEs used in clinical documents. Given the increasing use of CDEs in many studies and real-world clinical documentation, CMDO will be a useful tool for integrating numerous CDEs from different research projects and clinical documents. The CMDO Browser and CMDO-enabled CDE Browser make it easy to search, share, and reuse CDEs, and also effectively integrate and manage CDEs from different studies and clinical documents.This research was supported by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (grant number:HI18C2386). KHIDI had no participation in the study design or data collection and analysis process. KHIDI did not participate in the writing of the manuscript

Combined effects of aerobic exercise and 40-Hz light flicker exposure on early cognitive impairments in Alzheimer’s disease of 3×Tg mice

Alzheimer’s disease (AD) is a progressive degenerative brain disease and the primary cause of dementia. At an early stage, AD is generally characterized by short-term memory impairment, owing to dysfunctions of the cortex and hippocampus. We previously reported that a combination of exercise and 40-Hz light flickering can protect against AD-related neuroinflammation, gamma oscillations, reduction in Aβ, and cognitive decline. Therefore, we sought to extend our previous findings to the 5-mo-old 3×Tg-AD mouse model to examine whether the same favorable effects occur in earlier stages of cognitive dysfunction. We investigated the effects of 12 wk of exercise combined with 40-Hz light flickering on cognitive function by analyzing neuroinflammation, mitochondrial function, and neuroplasticity in the hippocampus in a 3×Tg-AD mouse model. Five-month-old 3×Tg-AD mice performed 12 wk of exercise with 40-Hz light flickering administered independently and in combination. Spatial learning and memory, long-term memory, hippocampal Aβ, tau, neuroinflammation, proinflammatory cytokine expression, mitochondrial function, and neuroplasticity were analyzed. Aβ and tau proteins levels were significantly reduced in the early stage of AD, resulting in protection against cognitive decline by reducing neuroinflammation and proinflammatory cytokines. Furthermore, mitochondrial function improved, apoptosis was reduced, and synapse-related protein expression increased. Overall, exercise with 40-Hz light flickering was significantly more effective than exercise or 40-Hz light flickering alone, and the improvement was comparable to the levels in the nontransgenic aged-match control group. Our results indicate a synergistic effect of exercise and 40-Hz light flickering on pathological improvements in the hippocampus during early AD-associated cognitive impairment