Functional connectivity of the amygdala in relation to high stress and low mindfulness.

BACKGROUND: High psychological stress has been associated with several brain functional changes, including functional connectivity (FC) alterations in regions such as the prefrontal cortex and the amygdala. This study explored FC alterations associated with high perceived stress, and also investigated whether these neuroimaging features were correlated with low levels of mindfulness. METHODS: This study included 29 adults (12 males and 17 females; mean age: 27.6 ± 3.2) who complained of moderate or higher perceived stress and 31 adults (17 males and 14 females; mean age: 29.2 ± 7.2) who complained of low-level stress on the questionnaire scale. Seed-based resting-state FC analysis was conducted to compare between high and low stress groups. The dorsolateral prefrontal cortex (DLPFC), the ventromedial prefrontal cortex (VMPFC) and the amygdala were selected as seeds. RESULTS: High stress group showed weaker left amygdala-based FC in the left cerebellum crus II and the left orbitofrontal cortex compared with low stress group. High stress group had weaker FC between the left DLPFC and the left inferior parietal lobule. On the contrary, high stress group had stronger FC between the left VMPFC and the left caudate compared with low stress group. Weaker FC between the amygdala and the cerebellum crus II was correlated with lower level of awareness facet of mindfulness. CONCLUSIONS: Those with high perceived stress showed low levels of mindfulness and several FC alterations centered on the prefrontal cortex and amygdala. Our findings also suggest that weak amygdala-based FC alterations associated with high psychological stress are related to low-level awareness facet of mindfulness.

The mediating effect of attentional impulsivity between mindfulness and problematic smartphone use.

OBJECTIVE: Problematic smartphone use has been linked to lower levels of mindfulness, impaired attentional function, and higher impulsivity. This study aimed to identify the psychological mechanisms of problematic smartphone use by exploring the relationship between addictive smartphone use, mindfulness, attentional function and impulsivity. METHODS: Ninety participants were evaluated with the smartphone addiction proneness scale and classified into the problematic smartphone use group (n = 42; 24 women; mean age: 27.6 ± 7.2 years) or normal use group (n = 48; 22 women; mean age: 30.1 ± 5.7 years). All participants completed self-report questionnaires evaluating their trait impulsivity and mindfulness and attention tests that assessed selective, sustained and divided attention. We compared the variables between the groups and explored the relationship between mindfulness, attentional function, impulsivity and addictive smartphone use through mediation analysis. RESULTS: The problematic smartphone use group showed higher trait impulsivity and lower mindfulness than the normal use group. There were no significant group differences in performance on attention tests. Levels of addictive smartphone use were significantly correlated with higher levels of trait impulsivity and lower levels of mindfulness, but not with performance on attention tests. Mediation analysis showed that acting with awareness, an aspect of mindfulness, reduces the degree of addictive smartphone use through attentional impulsivity, one of the trait impulsivity. CONCLUSION: Acting without sufficient awareness could influence addictive smartphone use by mediating attentional impulsivity. This supports that executive control deficits, reflected in high attentional impulsivity, contribute to problematic smartphone use. Our findings imply that mindfulness-based interventions can enhance executive control over smartphone use by promoting awareness.

Development of a cervical cancer prevention text-messaging program for women living with HIV.

Cervical cancer screening and human papillomavirus (HPV) vaccination are critical for those immunocompromised due to human immunodeficiency virus (HIV). Health education programs, including text messaging, can effectively improve knowledge of cervical cancer and recommended screening. This paper describes the data-driven development of a 4-week text-messaging intervention to improve HPV and cervical cancer knowledge among women living with HIV (WLH). This study reports data from surveys (n = 81; January 2020 to September 2021) and focus group discussions (FGDs, n = 39; April-June 2020) conducted among WLH in the DC area. While most WLH revealed that their usual sources of health information were through in-person group sessions, they pointed out that these were impractical options due to the coronavirus 2019 pandemic. They noted that a text-messaging intervention was feasible and acceptable. FGD participants' responses structured around the Protection Motivation Theory constructs informed the text-messaging library, covering topics such as (I) understanding of cervical cancer and HPV, (II) cervical cancer prevention and (III) HPV self-sampling. The utilization of low-cost and easily accessible health education interventions, such as mobile-based text messaging, can effectively increase knowledge and awareness of cervical cancer in populations that have been historically difficult to access and during times when health services are disrupted such as during a global pandemic or public health emergency.

Effect of heavy metals on the energy metabolism in the brackish water flea Diaphanosoma celebensis.

Heavy metals such as lead (Pb), cadmium (Cd), and arsenic (As) are of great concern in aquatic ecosystems because of their global distribution, persistence, and biomagnification via the food web. They can induce the expression of cellular protective systems (e.g., detoxification enzymes and antioxidant enzymes) to protect organisms from oxidative stress, which is a high-energy-consuming process. Thus, energy reserves (e.g., glycogen, lipids, and proteins) are utilized to maintain metabolic homeostasis. Although a few studies have suggested that heavy metal stress can modulate the metabolic cycle in crustaceans, information on changes in energy metabolism under metal pollution remains lacking in planktonic crustaceans. In the present study, the activity of digestive enzymes (amylase, trypsin, and lipase) and the contents of energy storage molecules (glycogen, lipid, and protein) were examined in the brackish water flea Diaphanosoma celebensis exposed to Cd, Pb, and As for 48 h. Transcriptional modulation of the three AMP-activated protein kinase (AMPK) and metabolic pathway-related genes was further investigated. Amylase activity was highly increased in all heavy metal-exposed groups, whereas trypsin activity was reduced in Cd- and As-exposed groups. While glycogen content was increased in all exposed groups in a concentration-dependent manner, lipid content was reduced at higher concentrations of heavy metals. The expression of AMPKs and metabolic pathway-related genes was distinct among heavy metals. In particular, Cd activated the transcription of AMPK-, glucose/lipid metabolism-, and protein synthesis-related genes. Our findings indicate that Cd can disrupt energy metabolism, and may be a potent metabolic toxicant in D. celebensis. This study provides insights into the molecular mode of action of heavy metal pollution on the energy metabolism in planktonic crustaceans.

Microplastics disrupt energy metabolism in the brackish water flea Diaphanosoma celebensis.

Energy metabolism is crucial for normal biological processes, such as growth, development, and reproduction. Microplastics disrupt energy homeostasis by modulating the digestive capacity and contents of energy reserves to overcome stress. This study investigated the modulation of digestive enzyme activity and energy reserves in the brackish water flea Diaphanosoma celebensis exposed to polystyrene (PS) beads (0.05-, 0.5-, 6-µm) for 48 h, and examined transcriptional changes in digestive enzyme-coding genes and AMP-activated protein kinase (AMPK) signaling pathway genes. PS particle size differentially modulated digestive enzyme activity, energy molecule content (glycogen, protein, and lipids), and metabolism-related gene expression. In particular, the 0.5-µm PS had the most significant effect on digestive enzyme activity. In contrast, the 0.05-µm PS caused significant metabolic disorder following a decrease in total energy budget (Ea). These findings suggest that PS beads can modulate energy metabolism through different modes depending on the bead size.

Metabolomic analysis of combined exposure to microplastics and methylmercury in the brackish water flea Diaphanosoma celebensis.

Owing to their widespread distribution and high bioaccumulation, microplastics (MPs) and mercury (Hg) are considered major threats to the ocean. MP interacts with Hg because of its high adsorption properties. However, their toxicological interactions with marine organisms, especially combined effects at the molecular level, are poorly understood. This study investigated the single and combined effects of MP and Hg on the metabolic profile of the brackish water flea Diaphanosoma celebensis. A total of 238 metabolites were significantly affected by MP, Hg, or MP + Hg. Metabolite perturbation patterns showed that toxicity of Hg and MP + Hg was similar and that of MP was not significant. Among the 223 metabolites affected by Hg, profiles of 32 unannotated metabolites were significantly different from those of MP + Hg, and combined effects of MP + Hg decreased the effect of Hg on 25 of these metabolites. Only 11 annotated metabolites were significantly affected by Hg or MP + Hg and were related to carbohydrate, lipid, vitamin, and ecdysteroid metabolism. Ten metabolites were decreased by Hg and MP + Hg and were not significantly different between the exposure groups. Enrichment analysis showed that galactose, starch, and sucrose metabolism were the most affected pathways. These findings suggest that MP has negligible toxic effect, and Hg can induce energy depletion, membrane damage, and disruption of growth, development, and reproduction. Although the impact of MP was negligible, the combined effects of MP + Hg could be metabolite specific. This study provides better understanding of the combined effects of MP and Hg on marine organisms.

Perceptions and patient care needs among hepatitis B patients during COVID-19.

BACKGROUND: The novel coronavirus of 2019 (COVID-19) has been and continues to be a rapidly developing public health crisis, that has also disrupted routine and maintenance health care for people living with chronic conditions. Some of these chronic conditions also put individuals at increased risk of COVID-19 complications, particularly if the condition is not under control. For these reasons, the exploratory study reported here examined the needs and preparedness of patients at a community health organization that specifically provides hepatitis B virus (HBV) care for high-risk groups that had previously tested positive for HBV. METHODS: Current study utilized exploratory analysis of qualitative COVID-19-related statements collected during calls to a total of 44 patients reached during April and May, 2020 in the Washington D.C. area. Researchers worked with a community based non-profit organization to reach current HBV + and HCV + patients to provide retention in care and assess patient needs in maintaining management of their condition adapted to include offering medication refills, telehealth, and other resources. We gathered emergent themes, using socio-ecological framework, regarding capacity and needs for managing their chronic condition in a vulnerable population during the initial, most interrupted, time period of a global public health crisis. RESULTS: From the notes of the calls, five thematic categories emerged: COVID-19 prevention awareness, assistance program access, medical resource access, access to knowledge and awareness about assistance programs, and needs and barriers. From these five themes, providers can develop strategies to better prepare their patients and provide care to patients with chronic conditions during major disruptions. CONCLUSIONS: Future recommendations include increasing hepatitis and COVID-19 vaccine efforts, collaborating with community partners, and screening and understanding social determinants of health that affect racial and ethnic minorities.

Process evaluation of an academic-community-government partnership to reduce liver diseases attributable to hepatitis B virus.

BACKGROUND: Racial/ethnic minorities have higher incidence and mortality rates of liver cancer, or hepatocellular carcinoma, than non-Hispanic Whites. As such, the Washington-Baltimore Metropolitan Area Hepatitis B Virus (WB-HBV) Demonstration Project, a community-based participatory research (CBPR)-driven academic-community-government (ACG) partnership, was established in 2019 to address disparities and implement strategies to improve the HBV screening and vaccination infrastructure for at-risk communities. CBPR is a partnership of community members, organizational leaders, and academic researchers with a common aim to collectively share and contribute their input at every phase of the project. Herein, we describe the process evaluation of the WB-HBV Project and extract themes and insights to benefit future ACG partnerships and community-engaged research. The process evaluation has been conducted to determine whether CBPR-driven partnership and programmatic activities have been implemented as intended and have resulted in building expanded research capacity for future ACG partnership HBV community-level initiatives. METHODS: A WB-HBV Project Task Force was convened and comprised of eight organizations: four community organizations, three government organizations, and one academic institution. Through a mixed-methods process evaluation, an online survey and key informant interviews were conducted to provide context for program implementation barriers and facilitators. Descriptive statistics were conducted, and interviews were recorded, transcribed, and thematically coded. RESULTS: The survey was completed by 14 of 20 partnership members (70.0%): two academic, eight community, and four government members. Partnership members showed general agreement across 14 domains: organization and structure of meetings; trust; decisions; impact; general satisfaction; strategic planning; ACG policy impact; community-based participatory research and government; participation in meetings; assessment of participation; partnership operations and capacity; communication; challenges/limitations associated with ACG involvement; and benefits compared to challenges associated with ACG involvement. Qualitative interviews were conducted with 15 of the 20 members (75.0%): two academic, nine community, and four government members. Four themes emerged: partnership involvement, project goals and accomplishments, project challenges and barriers, and partnership involvement in government or policy. CONCLUSIONS: The process evaluation presents insights into developing strategies to enhance partnership functioning and increase the ability of present and future ACG partnerships to improve community health outcomes.

HPV knowledge, screening barriers and facilitators, and sources of health information among women living with HIV: perspectives from the DC community during the COVID-19 pandemic.

BACKGROUND: High-risk human papillomavirus (HPV) causes 99% of cervical cancer cases. Despite available prevention methods through the HPV vaccine and two screening modalities, women continue to die from cervical cancer worldwide. Cervical cancer is preventable, yet affects a great number of women living with HIV (WLH). Low screening rates among WLH further exacerbate their already high risk of developing cervical cancer due to immunosuppression. This study explores WLH's current cervical cancer knowledge, screening barriers and facilitators, and sources of health information. METHODS: Focus group discussions were conducted with 39 WLH aged 21 years old or older, who resided in the Washington-Baltimore Metropolitan Area. Emergent themes were classified and organized into overarching domains and assembled with representative quotations. RESULTS: The women had limited knowledge of HPV and the cervical cancer screening guidelines for WLH. Coronavirus 2019 (COVID-19) pandemic has amplified screening barriers due to decreased accessibility to usual medical appointment and cervical cancer screenings. Screening facilitators included knowing someone diagnosed with cervical cancer and provider recommendations. WLH indicated that they obtained health information through in-person education (providers, peer groups) and written literature. Due to the pandemic, they also had to increasingly rely on remote and technology-based communication channels such as the internet, social media, television, radio, email, and short message service (SMS) text messaging. CONCLUSIONS: Future health interventions need to explore the possibility of sharing messages and increasing cervical cancer and HPV knowledge of WLH through the use of SMS and other technology-based channels.

Cervical Cancer Prevention and High-Risk HPV Self-Sampling Awareness and Acceptability among Women Living with HIV: A Qualitative Investigation from the Patients' and Providers' Perspectives.

Routine cervical cancer screening is important for women living with HIV (WLH) due to the greater incidence and persistence of high-risk HPV (HR-HPV) infection. HR-HPV self-sampling has been proposed to overcome barriers to in-office cervical cancer screening in underserved populations. However, little is known about baseline knowledge of HR-HPV and the acceptability of HR-HPV self-sampling among WLH. This paper describes WLH's experiences and needs regarding cervical cancer screening, specifically HR-HPV self-sampling, and seeks to reconcile their experiences with the views of their providers. In total, 10 providers and 39 WLH participated in semi-structured interviews and group discussions, respectively. Knowledge of cervical cancer and HR-HPV was generally limited among WLH; when present, it was often due to personal experience of or proximity to someone affected by cervical cancer. Most WLH were not familiar with HR-HPV self-sampling but, despite some of the providers' skepticism, expressed their willingness to participate in a mail-based HR-HPV self-sampling intervention and highlighted convenience, ease of use, and affordability as facilitators to the uptake of HR-HPV self-sampling. The experiences identified can be used to guide patient-centered communication aimed at improving cervical cancer knowledge and to inform interventions, such as HR-HPV self-sampling, designed to increase cervical cancer screening among under-screened WLH.

Development and evaluation of a mobile-optimized daily self-rating depression screening app: A preliminary study.

The aims of this study were to design a mobile app that would record daily self-reported Korean version of the Center for Epidemiologic Studies Depression Scale-Revised (K-CESD-R) ratings in a "Yes" or "No" format, develop two different algorithms for converting mobile K-CESD-R scores in a binary format into scores in a 5-point response format, and determine which algorithm would be more appropriately applied to the newly developed app. Algorithm (A) was designed to improve the scoring system of the 2-week delayed retrospective recall-based original K-CESD-R scale, and algorithm (B) was designed to further refine the scoring of the 24-hour delayed prospective recall-based mobile K-CESD-R scale applied with algorithm (A). To calculate total mobile K-CESD-R scores, each algorithm applied certain cut-off criteria for a 5-point scale with different inter-point intervals, defined by the ratio of the total number of times that users responded "Yes" to each item to the number of days that users reported daily depressive symptom ratings during the 2-week study period. Twenty participants were asked to complete a K-CESD-R Mobile assessment daily for 2 weeks and an original K-CESD-R assessment delivered to their e-mail accounts at the end of the 2-week study period. There was a significant difference between original and mobile algorithm (B) scores but not between original and mobile algorithm (A) scores. Of the 20 participants, 4 scored at or above the cut-off criterion (≥13) on either the original K-CESD-R (n = 4) or the mobile K-CESD-R converted with algorithm (A) (n = 3) or algorithm (B) (n = 1). However, all participants were assessed as being below threshold for a diagnosis of a mental disorder during a clinician-administered diagnostic interview. Therefore, the K-CESD-R Mobile app using algorithm (B) could be a more potential candidate for a depression screening tool than the K-CESD-R Mobile app using algorithm (A).

Spatial variation of bone biomechanical properties around a dental implant using nanoindentation: a case study.

The aim of the study was to evaluate the spatial variations in the biomechanical properties of the bone around the implants retrieved from human subjects due to fixture head fracture after almost 20 years of loading. The implant-in-bone specimens were prepared for the histomorphometry and nanoindentation test to measure the bone-to-implant contact ratio (BIC ratio) and elastic modulus (E) of peri-implant bone. The indentations were performed in the up, center, down, and away regions of the bone tissues within all the thread spaces. The BIC ratios were 91.0% for Patient #1 and 95.8% for Patient #2. The E values assessed from the up region within the thread spaces were significantly higher than those measured from the center region. The elastic properties assessed from center and down regions within the thread spaces were similar to those assessed from the away region. The representative E values showed no significant thread-dependent linear trend. Within the limitation of this study, the peri-implant bone tissue showed spatial variation of its elastic modulus after long-term functioning.

Transcatheter intra-arterial infusion of doxorubicin loaded porous magnetic nano-clusters with iodinated oil for the treatment of liver cancer.

A promising strategy for liver cancer treatment is to deliver chemotherapeutic agents with multifunctional carriers into the tumor tissue via intra-arterial (IA) transcatheter infusion. These carriers should release drugs within the target tissue for prolonged periods and permit intra-procedural multi-modal imaging of selective tumor delivery. This targeted transcatheter delivery approach is enabled via the arterial blood supply to liver tumors and utilized in current clinical practice which is called chemoembolization or radioembolization. During our study, we developed Doxorubicin (Dox) loaded porous magnetic nano-clusters (Dox-pMNCs). The porous structure and carboxylic groups on the MNCs achieved high-drug loading efficiency and sustained drug release, along with magnetic properties resulting in high MRI T2-weighted image contrast. Dox-pMNC within iodinated oil, Dox-pMNCs, and Dox within iodinated oil were infused via hepatic arteries to target liver tumors in a rabbit model. MRI and histological evaluations revealed that the long-term drug release and retention of Dox-pMNCs within iodinated oil induced significantly enhanced liver cancer cell death.

Development of a multimodal imaging probe by encapsulating iron oxide nanoparticles with functionalized amphiphiles for lymph node imaging.

AIM: We tried to develop a multimodal iron oxide nanoparticles (IO NP) imaging probe by an encapsulation method using specific amphiphiles for (68)Ga-labeling and lymph node-targeting. MATERIALS & METHODS: Nanoparticles (NPs) were encapsulated with a solution containing polysorbate 60 and the amphiphiles. The prepared NPs were labeled with (68)Ga and tested in vitro and in vivo. RESULTS: Prepared 1,4,7-triazacyclononane-1,4,7-triacetic acid-IO-Mannose (NOTA-IO-Man) showed a narrow size distribution, and no significant aggregation or degradation under harsh conditions. The relaxivity coefficient of (68)Ga-NOTA-IO-Man was higher than that of ferumoxide. The accumulation of (68)Ga-NOTA-IO-Man in the lymph node after injection into rat's footpad was confirmed by both positron emission tomography and MRI. CONCLUSION: We successfully developed PET/MRI dual-modality imaging probe targeting lymph nodes by using the facile encapsulation method.

High resolution in vivo 31P-MRS of the liver: potential advantages in the assessment of non-alcoholic fatty liver disease.

BACKGROUND: Biopsy remains the current gold-standard for assessing non-alcoholic fatty liver disease (NAFLD). To develop a non-invasive means of assessing the disease, 31P magnetic resonance spectroscopy (31P-MRS) has been explored, but the severe spectral overlaps and low signal-to-noise-ratio in 31P-MRS spectra at clinical field strength are clearly limiting factors. PURPOSE: To investigate potential advantages of high resolution in vivo 31P-MRS in assessing NAFLD. MATERIAL AND METHODS: The study was conducted at 9.4T in control and carbon tetrachloride (CCl4)-treated rats. Rats were divided according to histopathologic findings into a control group (n = 15), a non-alcoholic steatohepatitis group (n = 17), and a cirrhosis group (n = 12). Data were presented with different reference peaks that are commonly used for peak normalization such as total phosphorous signal, phosphomonoester + phosphodiester (PME + PDE), and nucleotide triphosphate (NTP). Then, multivariate analyses were performed. RESULTS: In all spectra PME and PDE were well resolved into phosphoethanolamine (PE) and phosphocholine (PC), and into glycerophosphorylethanolamine (GPE) and glycerophosphorylcholine (GPC), respectively. Those MRS measures quantifiable only in highly resolved spectra had higher correlations with histology than those conventional MRS measures such as PME, PDE, and NTP. The optimized partial least-squares discriminant analysis (PLS-DA) model correctly classified 79% (22/28) of the rats in the training set and correctly predicted 69% (11/16) of the rats in the test set. CONCLUSION: PE, PC, GPE, GPC, and nicotinamide adenine dinucleotide phosphate (NADP) that can be separately quantifiable in highly resolved spectra may further improve the potential efficacy of 31P-MRS in the diagnosis of NAFLD.

The intratumoral administration of ferucarbotran conjugated with doxorubicin improved therapeutic effect by magnetic hyperthermia combined with pharmacotherapy in a hepatocellular carcinoma model.

BACKGROUND: Local hyperthermia of tumor in conjunction with chemotherapy is a promising strategy for cancer treatment. The aim of this study was to evaluate the efficacy of intratumoral delivery of clinically approved magnetic nanoparticles (MNPs) conjugated with doxorubicin to simultaneously induce magnetic hyperthermia and drug delivery in a hepatocellular carcinoma (HCC) model. MATERIALS AND METHODS: HCC cells expressing luciferase were implanted into the flank of BALB/c-nu mice (n = 19). When the tumor diameter reached 7-8 mm, the animals were divided into four groups according to the injected agents: group A (normal saline, n = 4), group B (doxorubicin, n = 5), group C (MNP, n = 5), and group D (MNP/doxorubicin complex, n = 5). Animals were exposed to an alternating magnetic field (AMF) to receive magnetic hyperthermia, and intratumoral temperature changes were measured. RESULTS: The rise in temperature of the tumors was 1.88 ± 0.21°C in group A, 0.96 ± 1.05°C in B, 7.93 ± 1.99°C in C, and 8.95 ± 1.31°C in D. The RSI of the tumors at day 14 post-treatment was significantly lower in group D (0.31 ± 0.20) than in group A (2.23 ± 1.14), B (0.94 ± 0.47), and C (1.02 ± 0.21). The apoptosis rates of the tumors were 11.52 ± 3.10% in group A, 23.0 ± 7.68% in B, 25.4 ± 3.36% in C, and 39.0 ± 13.2% in D, respectively. CONCLUSIONS: The intratumoral injection of ferucarbotran conjugated with doxorubicin shows an improved therapeutic effect compared with doxorubicin or ferucarbotran alone when the complex is injected into HCC tissues exposed to AMF for magnetic hyperthermia. This strategy of combining doxorubicin and MNP-induced magnetic hyperthermia exhibits a synergic effect on inhibiting tumor growth in an HCC model.

Down-regulation of estrogen receptor α (ERα) transcriptional activity by p27 is mediated by inhibition of ERα nuclear localization and modulation of the ERα transcriptional complex.

To investigate the role of p27 on estrogen receptor (ER)α-mediated transcription, we generated MCF-7 cells with knocked down p27 via retroviral delivery of p27 shRNA. Suppression of p27 expression in MCF-7 cells resulted in up-regulation of ERα-mediated transcription by estradiol compared to the levels in control MCF-7 cells. Accordingly, transient transfection studies in 293T cells revealed that overexpression of p27 reduced ERα-mediated transcription. The effect of p27 on ERα transcriptional activity was independent of cell cycle arrest by p27, as cell cycle arrest induced by serum starvation did not significantly affect ERα-mediated transcription. Further, we observed that p27 inhibited nuclear localization of ERα, and that p27 was associated with ERα in the cytoplasm. We also investigated the role of p27 in the modulation of ERα transcriptional activity in the nucleus. We found that p27 negatively modulated ERα transcriptional activity by inhibiting association of cyclin D1 with ERα and recruiting BRCA1 to ERα transcriptional complex. Taken together, these data suggest that p27 inhibits ERα transcriptional activity by two independent mechanisms, namely, physical nuclear exclusion of ERα, and modulation of the ERα transcriptional complex.

Induction of apoptotic cell death by Pharbitis nil extract in HER2-overexpressing MCF-7 cells.

AIM OF THE STUDY: We performed this study to investigate the anti-cancer activity of Pharbitis nil (PN) ethanol extract which has been used for herbal medicinal treatment against diseases in East Asia. MATERIALS AND METHODS: We analyzed the effects of PN extract on proliferation of breast cancer cell lines, MCF-7 control vector (vec) and MCF-7 human epidermal growth factor receptor 2 (HER2) cells engineered to overexpress oncogenic HER2 via retroviral infection. We performed the proliferation assay to measure the growth rate of the cells. FACS analysis was used to analyze the cell cycle. Western blot analysis was used to investigate the effect of PN on the level and activation of intracellular molecules. RESULTS: We found that PN extract inhibited the proliferation of both MCF-7 vec and MCF-7 HER2 cells. This growth inhibition was accompanied with the increase of sub G0/G1 apoptotic fractions. When we check the efficiency of PN on the level of intracellular signaling molecules, we found that PN extract induced the inhibition of phosphorylation of HER2 and its downstream effectors, Akt and extracellular signal-regulated kinases (ERK). Active forms of both Akt and ERK were gradually decreased in PN-treated MCF-7 vec and MCF-7 HER2 cells suggesting that the growth suppressive activity of PN is related to signaling pathway. The level of cyclin D also diminished in PN-treated both cells suggesting that PN may inhibit the growth of MCF-7 vec and MCF-7 HER2 cells by perturbing cell cycle progression. It should be noted that PN decreased the growth rate of both MCF-7 vec and MCF-7 HER2 cells without changing the level and activation of p53. CONCLUSION: PN extract suppressed the proliferation rate of HER-2 overexpressing MCF-7 breast cancer cells inducing apoptotic cell death in vitro. Our data demonstrates that PN extracts contain useful anti-tumor activity especially against HER2 overexpressing breast cancer.

Danshen (Salvia miltiorrhiza) extract inhibits proliferation of breast cancer cells via modulation of Akt activity and p27 level.

Danshen is widely used in traditional Chinese medicine, often in combination with other herbs. To check the effect of Danshen on the proliferation of breast cancer cells, Danshen extract was used to treat MCF-7 and MCF-7 HER2 cells, the latter of which overexpresses HER2. HER2 is a receptor tyrosine kinase, and is involved in signal transduction pathways leading to tumor cell proliferation. MTT and cell proliferation assays revealed that Danshen strongly inhibited the proliferation of both MCF-7 vec cells and MCF-7 HER2 cells. Flow cytometry analyses indicated that Danshen induced cell cycle delay in the G1 phase. HER2 expression was shown to confer resistance to Danshen-induced inhibition of proliferation and cell cycle delay, suggesting that HER2 is responsible for the resistance to Danshen. Danshen treatment induced the down-regulation of Akt phosphorylation and an increase in p27 in MCF-7 vec and MCF-7 HER2 cells. Nevertheless, MCF-7 HER2 cells were more resistant to the Danshen-induced inhibition of Akt phosphorylation and p27 up-regulation.