Coping with Non-COVID-19 Health Problems Through Communicative Action in Cyberspace.

This study investigated how the online health information behaviors of U.S. adults with illnesses unrelated to COVID-19 virus infection affected their coping with health problems and concerns during the COVID-19 pandemic. Guided by the cybercoping model (Kim & Lee, 2014), the study examined associations between these patients' online information behaviors (information seeking and information forwarding) and coping outcomes (health problems and affective states). The study further explored the mediating roles of health coping processes (problem-and emotion-focused) in the associations between these information behaviors and coping outcomes. Survey data from 687 participants were analyzed using structural equation modeling. The results highlighted the significance of information forwarding in enhancing both coping processes and outcomes, while information seeking enhanced problem-focused coping and health-problem coping outcomes alone. These associations were more pronounced among U.S. adults without chronic conditions than among those with chronic illnesses. These findings' implications, the study's limitations, and suggestions for future research were also addressed.

An Oscillatory Path to Vaccination: The Roles of Normative and Epistemic Factors in Explaining Vaccination Hesitancy in COVID-19.

This study examined the roles of normative and epistemic factors in influencing individuals' reluctance to be vaccinated during the COVID-19 pandemic. Individuals' ethical orientations (IEO; teleology vs. deontology) were introduced as normative characteristics, while COVID-19 vaccine conspiracy beliefs and vaccine knowledge were addressed as issue-specific epistemic factors. We conducted two online surveys to investigate each of these three factors' influences on the level of Americans' reluctance to receive COVID-19 vaccines. Combinations of these factors that predict COVID-19 vaccination hesitancy levels were also explored to provide integrated perspectives in the specific vaccination context. Our findings demonstrated the positive association between IEO and reluctance to receive COVID-19 vaccines. Significant interactions between 1) COVID-19 vaccine conspiracy beliefs and IEO and 2) conspiracy beliefs and vaccine knowledge were also identified. Implications, limitations, and suggestions for future study were addressed.

Downregulated pol-miR-140-3p induces the expression of the kinesin family member 5A against Streptococcus parauberis infection in olive flounder.

MicroRNAs (miRNAs) are small non-coding RNAs that participate in various biological and cellular processes by regulating target gene expression. miRNAs are also known to play vital roles in the pathogenesis of various diseases, including infections, as well as the disease progression and defense responses. In this study, we examined the expression levels of pol-miR-140-3p and its target gene, kinesin family member 5A (KIF5A), in association with the Streptococcus parauberis (S. parauberis) infection, a major bacterial pathogen that causes streptococcosis in olive flounder (Paralichthys olivaceus). KIF5A is a heavy chain isoform of kinesin-1, which is known to be brain-specific, and this study is the first examination of KIF5A expression related to the regulation of miRNA in olive flounder (named PoKIF5A). There were significant differences in expression levels between infected and healthy olive flounder as the expression of pol-miR-140-3p in the infected fish was lower than that in the control, while the expression of PoKIF5A was higher in the infected fish than in the healthy controls. These contradictory results suggest that downregulated pol-miR-140-3p induces the expression of PoKIF5A against S. parauberis infection in olive flounder.

Grape seed powder increases gastrointestinal motility.

Grape seed is an important natural bioactive product with various health benefits. Interstitial cells of Cajal (ICCs) are pacemaker cells in the gastrointestinal (GI) tract. The present study investigated the effects of grape seed powder (GSP) on ICC properties and GI motility. GSP depolarized the pacemaker potentials of ICCs in a dose­dependent manner. Y25130 or SB269970 slightly inhibited GSP­induced effects. However, Y25130 and SB269970 together completely blocked GSP-induced effects. In the presence of inhibitors of protein kinase C, protein kinase A, or mitogen-activated protein kinase, GSP­induced ICC depolarization was inhibited. GSP increased the intestinal transit rate in normal mice and in mice with acetic acid-induced GI motility disorder. In addition, the levels of motilin and substance P were elevated after GSP dosing. These results demonstrate that GSP can regulate GI motility, and therefore, it is a potential therapeutic agent for treating GI motility disorders.

Alisma canaliculatum Extract Affects AGS Gastric Cancer Cells by Inducing Apoptosis.

The anti-cancer effects of Alisma canaliculatum extracts (ACE) were identified in AGS gastric cancer cells. Our results showed that ACE inhibited the growth of AGS cells, increased the proportion of sub-G1 phase cells, and depolarized the membrane potential of mitochondria. ACE-induced gastric cancer cell death was associated with Bcl-2, survivin and Bax level changes, and it activated caspase-3 and -9. In addition, it was involved in the activation of MAPKs and increased the reactive oxygen species (ROS). These results suggest that ACE induces apoptosis in AGS gastric cancer cells, and therefore, ACE may have the potential to treat gastric cancer.

Mechanics of Rumor Mills and Epistemic Motivational Processes of Food-related Rumor Spread: Interplay between Attitude and Issue Motivation.

This study tested the manner in which attitude toward an object of rumor affects people's epistemic motivation to solve a problem and to share a rumor, specifically on social media, using two rumors regarding food safety issues including McDonald's and genetically modified food. An online survey administered to 184 undergraduate students who use Twitter showed that negative attitudes increased the likelihood of rumor sharing, mediated by issue-related epistemic motivation. However, positive attitudes showed no effects on issue-related motivation and the likelihood of rumor sharing. Theoretical and practical implications are discussed.

Anticancer Activity of Continentalic Acid in B-Cell Lymphoma.

Aralia continentalis has been used in Korea as a folk remedy for arthralgia, rheumatism, and inflammation. However, its anti-lymphoma effect remains uncharacterized. Here, we demonstrate that A. continentalis extract and its three diterpenes efficiently kill B-lymphoma cells. Our in vitro and in vivo results suggest that the cytotoxic activities of continentalic acid, a major diterpene from A. continentalis extract, are specific towards cancer cells while leaving normal murine cells and tissues unharmed. Mechanistically, continentalic acid represses the expression of pro-survival Bcl-2 family members, such as Mcl-1 and Bcl-xL. It dissociates the mitochondrial membrane potential, leading to the stimulation of effector caspase 3/7 activities and, ultimately, cell death. Intriguingly, this agent therapeutically synergizes with roflumilast, a pan-PDE4 inhibitor that has been successfully repurposed for the treatment of aggressive B-cell malignancies in recent clinical tests. Our findings unveiled that A. continentalis extract and three of the plant's diterpenes exhibit anti-cancer activities. We also demonstrate the synergistic inhibitory effect of continentalic acid on the survival of B-lymphoma cells when combined with roflumilast. Taken in conjunction, continentalic acid may hold significant potential for the treatment of B-cell lymphoma.

Peptides encoded in the Streptococcus mutans RcrRPQ operon are essential for thermotolerance.

The MarR-like transcriptional regulator and two ABC transporters encoded by the rcrRPQ operon in the dental caries pathogen Streptococcus mutans have important regulatory roles related to oxidative stress tolerance, genetic competence and (p)ppGpp metabolism. A unique feature of the rcrRPQ operon, when compared to other bacteria, is the presence of two peptides, designated Pep1 and Pep2, encoded in alternative reading frames at the 3' end of rcrQ. Here, we show that the rcrRPQ operon, including Pep1 and 2, is essential for S. mutans to survive and maintain viability at elevated temperatures. No major changes in the levels of the heat shock proteins DnaK or GroEL that could account for the thermosensitivity of rcrRPQ mutants were observed. By introducing a single amino acid substitution into the comX gene that deletes an internally encoded peptide, XrpA, we found that XrpA is a contributing factor to the thermosensitive phenotype of a ΔrcrR strain. Overexpression of XrpA on a plasmid also caused a significant growth defect at 42 °C. Interestingly, loss of the gene for the RelA/SpoT homologue (RSH) enzyme, relA, restored growth of the ΔrcrR strain at 42 °C. During heat stress and when a stringent response was induced, levels of (p)ppGpp were elevated in the ΔrcrR strain. Deletion of relA in the ΔrcrR strain lowered the basal levels of (p)ppGpp to those observed in wild-type S. mutans. Thus, (p)ppGpp pools are dysregulated in ΔrcrR, which likely leads to aberrant control of transcriptional/translational processes and the thermosensitive phenotype. In summary, the genes and peptides encoded in the rcrRPQ operon are critical for thermotolerance, and in some strains these phenotypes are related to altered (p)ppGpp metabolism and increased production of the XrpA peptide.

The Traditional Medicine Banhasasim-Tang Depolarizes Pacemaker Potentials of Cultured Interstitial Cells of Cajal through M3 Muscarinic and 5-HT3 Receptors in Murine Small Intestine.

BACKGROUND: Banhasasim-tang (BHSST) is a classic herbal formulation in traditional Chinese medicine widely used for gastrointestinal (GI) tract motility disorder. We investigated the effects of BHSST on the pacemaker potentials of cultured interstitial cells of Cajal (ICCs) in small intestine in vitro and its effects on GI motor functions in vivo. METHODS: We isolated ICCs from the small intestines and recorded pacemaker potentials in cultured ICCs with the whole-cell patch-clamp configuration in vitro. Intestinal transit rates (ITR%) were investigated in normal mice and GI motility dysfunction (GMD) mouse models in vivo. RESULTS: BHSST (20-50 mg/mL) depolarized pacemaker potentials and decreased their amplitudes in a concentration-dependent manner. Pretreatment with methoctramine (a muscarinic M2 receptor antagonist) did not inhibit BHSST-induced pacemaker potential depolarization. However, when we applied 1,1-dimethyl-4-diphenylacetoxypiperidinium iodide (4-DAMP; a muscarinic M3 receptor antagonist), BHSST-induced effects were blocked. Pretreatment with Y25130 (a 5-HT3 receptor antagonist) blocked BHSST-induced effects in ICCs. In addition, when we applied 4-DAMP and Y25130 together, BHSST-induced effects were completely blocked. Pretreatment with Ca2+-free solution or thapsigargin inhibited BHSST-induced effects. Moreover, BHSST blocked both the transient receptor potential melastatin (TRPM) 7 and voltage-sensitive calcium-activated chloride (anoctamin-1, ANO1) channels. In normal mice, ITR% values were significantly increased by BHSST in a dose-dependent manner. The ITR% of GMD mice was significantly reduced relative to those of normal mice, which were significantly reversed by BHSST in a dose-dependent manner. CONCLUSION: These results suggested that BHSST depolarizes the pacemaker potentials of ICCs in a dose-dependent manner through the M3 and 5-HT3 receptors via internal and external Ca2+-dependent and TRPM7- and ANO1-independent pathways in vitro. Moreover, BHSST increased ITR% in vivo in normal mice and GMD mouse models. Taken together, the results of this study showed that BHSST had the potential for development as a prokinetic agent in GI motility function.

Rikkunshito Depolarizes Pacemaker Potentials of Cultured Interstitial Cells of Cajal through Ghrelin Receptors in Murine Small Intestine.

BACKGROUND: Rikkunshito has been used to treat gastrointestinal (GI) disorders. The purpose of this study was to investigate the effects of Rikkunshito, a traditional Japanese herbal medicine, on the pacemaker potentials of interstitial cells of Cajal (ICCs) from the small intestines of mice. METHODS: We isolated ICCs from the small intestines of mice, and the whole-cell patch-clamp configuration was used to record the pacemaker potentials in cultured ICCs and membrane currents. RESULTS: Rikkunshito depolarized ICC pacemaker potentials in a dose-dependent manner. Pretreatment with GSK1614343 or (D-Lys3)-growth hormone-releasing peptide-6 inhibited Rikkunshito-induced depolarization of pacemaker potentials. Intracellular GDP-ß-S inhibited Rikkunshito-induced effects. In Ca2+-free solution or in the presence of thapsigargin, Rikkunshito did not depolarize pacemaker potentials. Moreover, in the presence of U-73122 or xestospongin C, Rikkunshito-induced effects were inhibited. However, in the presence of staurosporine, Go6976 or Rottlerin, Rikkunshito depolarized pacemaker potentials. Furthermore, Rikkunshito inhibited both transient receptor potentials melastatin 7 (TRPM7) and Ca2+-activated Cl- channels (ANO1) currents. CONCLUSION: Rikkunshito depolarized pacemaker potentials of ICCs via ghrelin receptor and G protein through internal or external Ca2+-, phospholipase C-, and inositol triphosphate-dependent and protein kinase C-, TRPM7-, and ANO1-independent pathways. The study shows that Rikkunshito may alleviate GI motility disorders through its depolarizing effects on ICCs.

Effects of Chaihu-Shugan-San on Small Intestinal Interstitial Cells of Cajal in Mice.

Chaihu-Shugan-San (CSS) has been widely used as an alternative treatment for gastrointestinal (GI) diseases in East Asia. Interstitial cells of Cajal (ICCs) are pacemakers in the GI tract. In the present study, we examined the action of CSS on pacemaker potentials in cultured ICCs from the mouse small intestine in vitro and on GI motility in vivo. We used the electrophysiological methods to measure the pacemaker potentials in ICCs. GI motility was investigated by measuring intestinal transit rates (ITR). CSS inhibited the pacemaker potentials in a dose-dependent manner. The capsazepine did not block the effect of CSS. However, the effects of CSS were blocked by glibenclamide. In addition, NG-nitro-L-arginine methyl ester (L-NAME) also blocked the CSS-induced effects. Pretreatment with SQ-22536 or with KT-5720 did not suppress the effects of CSS; however, pretreatment with ODQ or KT-5823 did. Furthermore, CSS significantly suppressed murine ITR enhancement by neostigmine in vivo. These results suggest that CSS exerts inhibitory effects on the pacemaker potentials of ICCs via nitric oxide (NO)/cGMP and ATP-sensitive K+ channel dependent and transient receptor potential vanilloid 1 (TRPV1) channel independent pathways. Accordingly, CSS could provide the basis for the development of new treatments for GI motility dysfunction.

Radix Sophorae Flavescentis induces apoptosis through by Caspase, MAPK Activation and ROS Signaling Pathways in 5637 Human Bladder Cancer Cells.

The anti-cancer mechanisms of Radix Sophorae Flavescentis were investigated in 5637 bladder cancer cells. Radix Sophorae Flavescentis extract (RSF) (50­400 µg/ml) inhibited the proliferation of 5637 cells and increased sub­G1 phase ratios. RSF­induced cell death was associated with the down-regulation of B­cell lymphoma 2 (Bcl­2) and the up-regulation of Bcl­2 X­associated protein (Bax). RSF also activated caspase­3 and -9 and regulated the activations of mitogen-activated protein kinases (MAPKs). In addition, RSF increased intracellular reactive oxygen species (ROS) levels and depolarized the mitochondrial membrane potential. These findings suggest RSF induces apoptosis in 5637 bladder cancer cells and that it has potential use as a novel anti-cancer drug for bladder cancer.

Depolarization of pacemaker potentials by caffeic acid phenethyl ester in interstitial cells of Cajal from the murine small intestine.

Interstitial cells of Cajal (ICCs) are pacemaker cells in the gastrointestinal (GI) tract and generate pacemaker potentials. In this study, we investigated the effects of caffeic acid phenethyl ester (CAPE) on the pacemaker potentials of ICCs from the mouse small or large intestine. Using the whole-cell patch-clamp configuration, we found that CAPE depolarized the pacemaker potentials of cultured ICCs from the murine small intestine in a dose-dependent manner. The estrogen receptor (ER) ß antagonist PHTPP completely inhibited CAPE-induced depolarization, but the ERα antagonist BHPI did not. Intracellular GDP-ß-S and pretreatment with Ca2+-free solution or thapsigargin also blocked CAPE-induced depolarization. To investigate the mechanisms of CAPE-mediated depolarization of ICCs, we used the nonselective cation channel (NSCC) inhibitor flufenamic acid, the Cl- channel blocker, mitogen-activated protein kinase (MAPK) inhibitors PD98059, SB203580, or SP600125, and PI3 kinase inhibitor LY294002. All inhibitors blocked the CAPE-induced pacemaker potential depolarization of ICCs. These results suggest that CAPE induces pacemaker potential depolarization through ERß in a G protein, NSCC, Cl- channel, MAPK- and PI3 kinase dependent manner via intracellular and extracellular Ca2+ regulation in the murine small intestine. CAPE may therefore modulate GI motility by acting on ICCs in the murine small intestine.

Ashamed Caregivers: Self-Stigma, Information, and Coping among Dementia Patient Families.

The number of people living with dementia increases almost every year, and the majority of the care system for these individuals is often made up of close family members. This study investigates the relationship between family caregivers' cross-checking of information with healthcare providers and patient health outcomes. Specifically, we examined whether this relationship was mediated by caregivers' enhanced coping efficacy. We also tested the moderation effect of family caregivers' affiliate stigma on information cross-checking, coping efficacy, and coping outcomes. Using a survey of 226 family caregivers of dementia patients in South Korea, this study tested the moderated mediation model with the PROCESS macro. Results indicate that low affiliate stigma moderates coping efficacy on the relationship between information cross-checking and dementia patients' health outcomes. Further implications for family caregiving and general dementia care are discussed.

Anticariogenic Potential of Korean Native Plant Extracts against Streptococcus mutans.

Numerous chemically synthesized compounds are widely used in oral hygiene products. However, due to their potential risk, there is a need to improve the safety and quality of dental care by seeking alternative control agents such as those naturally found in plant materials. Here we assessed antibacterial potentials of extracts from 100 species of Korean native plants against Streptococcus mutans on cariogenesis. Among those, extracts from five plants (Arctii Fructus, Caryopteris incana, Aralia continentalis, Symplocarpus renifolius, and Lamium amplexicaule) showed a growth inhibition of S. mutans. The five extracts were further individually evaluated for their minimal inhibitory concentration and minimal bactericidal concentration. Interestingly, a synergistic antibacterial activity was observed with the combination of sodium fluoride and the plant extracts. To determine the anti-biofilm activity of plant extracts, S. mutans was treated with increasing concentrations of the extracts in the range from 1250 to 3750 µg/mL. When S. mutans was grown in the defined biofilm medium containing the individual extracts of 47 species, the biofilm amount markedly decreased compared to that of a negative control. Notably, the extract of S. renifolius significantly downregulated the gtf and spaP genes for synthesis of glucan and adhesive proteins in S. mutans, and L. amplexicaule decreased the expression of gtfD gene. Therefore, these results demonstrate that the five plant extracts modulate survival and pathogenesis of S. mutans by growth inhibition and downregulation of the gene(s) implicated in biofilm formation.

Digital Networked Information Society and Public Health: Problems and Promises of Networked Health Communication of Lay Publics.

This special issue of Health Communication compiles 10 articles to laud the promise and yet confront the problems in the digital networked information society related to public health. We present this anthology of symphony and cacophony of lay individuals' communicative actions in a digital networked information society. The collection of problems and promise of the new digital world may be a cornerstone joining two worlds-pre- and postdigital network society-and we hope this special issue will help better shape our future states of public health.

Justificatory Information Forefending in Digital Age: Self-Sealing Informational Conviction of Risky Health Behavior.

This study proposes the idea of justificatory information forefending, a cognitive process by which individuals accept information that confirms their preexisting health beliefs, and reject information that is dissonant with their attitudes. In light of the sheer volume of often contradictory information related to health that is frequently highlighted by the traditional media, this study sought to identify antecedents and outcomes of this justificatory information forefending. Results indicate that individuals who are exposed to contradictory health information, currently engage in risky health behavior, are comfortable using the Internet to search for information, and are currently taking steps to maintain their health are likely to actively select health information that confirms their preexisting notions about their health, and to reject information that is contradictory to their beliefs. Additionally, individuals who engage in justificatory information forefending were also found to continue to engage in risky health behavior. Implications for theory and practice are discussed.

CcpA and CodY Coordinate Acetate Metabolism in Streptococcus mutans.

In the dental caries pathogen Streptococcus mutans, phosphotransacetylase (Pta) and acetate kinase (Ack) convert pyruvate into acetate with the concomitant generation of ATP. The genes for this pathway are tightly regulated by multiple environmental and intracellular inputs, but the basis for differential expression of the genes for Pta and Ack in S. mutans had not been investigated. Here, we show that inactivation in S. mutans of ccpA or codY reduced the activity of the ackA promoter, whereas a ccpA mutant displayed elevated pta promoter activity. The interactions of CcpA with the promoter regions of both genes were observed using electrophoretic mobility shift and DNase protection assays. CodY bound to the ackA promoter region but only in the presence of branched-chain amino acids (BCAAs). DNase footprinting revealed that the upstream region of both genes contains two catabolite-responsive elements (cre1 and cre2) that can be bound by CcpA. Notably, the cre2 site of ackA overlaps with a CodY-binding site. The CcpA- and CodY-binding sites in the promoter region of both genes were further defined by site-directed mutagenesis. Some differences between the reported consensus CodY binding site and the region protected by S. mutans CodY were noted. Transcription of the pta and ackA genes in the ccpA mutant strain was markedly different at low pH relative to transcription at neutral pH. Thus, CcpA and CodY are direct regulators of transcription of ackA and pta in S. mutans that optimize acetate metabolism in response to carbohydrate, amino acid availability, and environmental pH.IMPORTANCE The human dental caries pathogen Streptococcus mutans is remarkably adept at coping with extended periods of carbohydrate limitation during fasting periods. The phosphotransacetylase-acetate kinase (Pta-Ack) pathway in S. mutans modulates carbohydrate flux and fine-tunes the ability of the organisms to cope with stressors that are commonly encountered in the oral cavity. Here, we show that CcpA controls transcription of the pta and ackA genes via direct interaction with the promoter regions of both genes and that branched-chain amino acids (BCAAs), particularly isoleucine, enhance the ability of CodY to bind to the promoter region of the ackA gene. A working model is proposed to explain how regulation of pta and ackA genes by these allosterically controlled regulatory proteins facilitates proper carbon flow and energy production, which are essential functions during infection and pathogenesis as carbohydrate and amino acid availability continually fluctuate.

Genetics and Physiology of Acetate Metabolism by the Pta-Ack Pathway of Streptococcus mutans.

In the dental caries pathogen Streptococcus mutans, phosphotransacetylase (Pta) catalyzes the conversion of acetyl coenzyme A (acetyl-CoA) to acetyl phosphate (AcP), which can be converted to acetate by acetate kinase (Ack), with the concomitant generation of ATP. A ΔackA mutant displayed enhanced accumulation of AcP under aerobic conditions, whereas little or no AcP was observed in the Δpta or Δpta ΔackA mutant. The Δpta and Δpta ΔackA mutants also had diminished ATP pools compared to the size of the ATP pool for the parental or ΔackA strain. Surprisingly, when exposed to oxidative stress, the Δpta ΔackA strain appeared to regain the capacity to produce AcP, with a concurrent increase in the size of the ATP pool compared to that for the parental strain. The ΔackA and Δpta ΔackA mutants exhibited enhanced (p)ppGpp accumulation, whereas the strain lacking Pta produced less (p)ppGpp than the wild-type strain. The ΔackA and Δpta ΔackA mutants displayed global changes in gene expression, as assessed by microarrays. All strains lacking Pta, which had defects in AcP production under aerobic conditions, were impaired in their abilities to form biofilms when glucose was the growth carbohydrate. Collectively, these data demonstrate the complex regulation of the Pta-Ack pathway and critical roles for these enzymes in processes that appear to be essential for the persistence and pathogenesis of S. mutans.

Discovery of novel peptides regulating competence development in Streptococcus mutans.

A MarR-like transcriptional repressor (RcrR) and two predicted ABC efflux pumps (RcrPQ) encoded by a single operon were recently shown to be dominant regulators of stress tolerance and development of genetic competence in the oral pathogen Streptococcus mutans. Here, we focused on polar (ΔrcrR-P) and nonpolar (ΔrcrR-NP) rcrR mutants, which are hyper- and nontransformable, respectively, to dissect the mechanisms by which these mutations impact competence. We discovered two open reading frames (ORFs) in the 3' end of the rcrQ gene that encode peptides of 27 and 42 amino acids (aa) which are also dramatically upregulated in the ΔrcrR-NP strain. Deletion of, or start codon mutations in, the ORFs for the peptides in the ΔrcrR-NP background restored competence and sensitivity to competence-stimulating peptide (CSP) to levels seen in the ΔrcrR-P strain. Overexpression of the peptides adversely affected competence development. Importantly, overexpression of mutant derivatives of the ABC exporters that lacked the peptides also resulted in impaired competence. FLAG-tagged versions of the peptides could be detected in S. mutans, and FLAG tagging of the peptides impaired their function. The competence phenotypes associated with the various mutations, and with overexpression of the peptides and ABC transporters, were correlated with the levels of ComX protein in cells. Collectively, these studies revealed multiple novel mechanisms for regulation of competence development by the components of the rcrRPQ operon. Given their intimate role in competence and stress tolerance, the rcrRPQ-encoded peptides may prove to be useful targets for therapeutics to diminish the virulence of S. mutans.