The endocannabinoid system is involved in the anxiety-like behavior induced by dual-frequency 2.65/0.8 GHz electromagnetic radiation in mice.

As wireless communication devices gain popularity, concerns about the potential risks of environmental exposure to complex frequency electromagnetic radiation (EMR) on mental health have become a public health issue. Historically, EMR research has predominantly focused on single- frequency electromagnetic waves, neglecting the study of multi-frequency electromagnetic waves, which more accurately represent everyday life. To address these concerns, our study compared the emotional effects of single-frequency and dual-frequency EMR while exploring potential molecular mechanisms and intervention targets. Our results revealed that single-frequency EMR at 2.65 or 0.8 GHz did not induce anxiety-like behavior in mice. However, exposure to dual-frequency EMR at 2.65/0.8 GHz significantly led to anxiety-like behavior in mice. Further analysis of mouse sera revealed substantial increases in corticosterone and corticotrophin releasing hormone levels following exposure to 2.65/0.8 GHz EMR. Transcriptome sequencing indicated a significant decrease in the expression of Cnr1, encoding cannabinoid receptor 1 Type (CB1R), in the cerebral. This finding was consistently verified through western blot analysis, revealing a substantial reduction in CB1R content. Additionally, a significant decrease in the endocannabinoid 2-arachidonoylglycerol was observed in the cerebral cortex. Remarkably, administering the cannabinoid receptor agonist Win55-212-2 significantly alleviated the anxiety-like behavior, and the cannabinoid receptor antagonist AM251 effectively counteracted the anti-anxiety effects of Win55-212-2. In summary, our research confirmed that dual-frequency EMR is more likely to induce anxiety-like behavior in mice than single-frequency EMR, with implications for the hypothalamic-pituitary-adrenal axis and the endocannabinoid system. Furthermore, our findings suggest that Win55-212-2 may represent a novel avenue for researching and developing anti-EMR drugs.

Measuring Spatial Access of Vulnerable Population to HIV Testing Facilities in the Baton Rouge Metropolitan Statistical Area, Louisiana.

Ensuring adequate and equitable access to affordable HIV testing is a crucial step toward ending the HIV epidemic (EHE). Using the high-burden Baton Rouge Metropolitan Statistical Area (MSA) as an example, we measure spatial access to HIV testing facilities for vulnerable populations and assess whether their access would improve if eliminating a considerable barrier-costs. Locations and status (free, low-cost, and full cost) of HIV testing facilities are searched on the Internet and confirmed through a field survey. Vulnerable populations include the uninsured and people living with HIV (PLWH), disaggregated from county-level HIV prevalence data. Spatial access is computed by a normalized urban-rural two-step floating catchment area (NUR2SFCA) method. Our survey confirms that only 11% and 37% of the 103 Internet-searched HIV testing facilities are indeed free and low-cost. Making more facilities cheaper or free increases the average access of PLWH, the uninsured, and the entire population but their geographic patterns vary. Free testing facilities, clustered in Baton Rouge city, are highly accessible to 82.6%, 69.4%, and 70.2% of three population groups living in East and West Baton Rouge Parish. In comparison, making all low-cost facilities free increases access in most outlying parishes but at the cost of reducing access in East Baton Rouge Parish, leaving west Livingston, north Iberville, and east Pointe Coupee Parish with the poorest access. Making all full-cost facilities cheaper or free exhibits a similar pattern. The study has important policy implications for where and how to improve access to HIV testing for vulnerable populations.

RESUMEN: Medimos el acceso espacial a las instalaciones de pruebas de VIH para poblaciones vulnerables y evaluamos si su acceso mejoraría si se eliminaran las barreras de costos, utilizando como ejemplo el área estadística metropolitana de Baton Rouge, que tiene una alta carga. Nuestra encuesta confirma que el 11% y el 37% de los 103 centros de pruebas de VIH buscados en Internet son efectivamente gratuitos y de bajo costo. Hacer que más instalaciones sean más baratas o gratuitas aumenta el acceso promedio de las PLWH, las personas sin seguro y toda la población, pero sus patrones geográficos varían. Las instalaciones de pruebas gratuitas, agrupadas en la ciudad de Baton Rouge, son muy accesibles para el 82,6%, el 69,4% y el 70,2% de los tres grupos de población del este y oeste de Baton Rouge. En comparación, hacer que las instalaciones de bajo costo sean gratuitas aumenta el acceso en las parroquias periféricas, pero a costa de reducir el acceso en East Baton Rouge. Hacer que las instalaciones de costo total sean más baratas o gratuitas muestra un patrón similar. El estudio tiene importantes implicaciones políticas para mejorar el acceso a las pruebas del VIH para las poblaciones vulnerables.

Characterizing the Traveling Oncology Workforce and Its Influence on Patient Travel Burden: A Claims-Based Approach.

PURPOSE: Oncology outreach is a common strategy for extending cancer care to rural patients. However, a nationwide characterization of the traveling workforce that enables this outreach is lacking, and the extent to which outreach reduces travel burden for rural patients is unknown. METHODS: This cross-sectional study analyzed a rural (nonurban) subset of a 100% fee-for-service sample of 355,139 Medicare beneficiaries with incident breast, colorectal, and lung cancers. Surgical, medical, and radiation oncologists were linked to patients using Part B claims, and traveling oncologists were identified by observing hospital service area (HSA) transition patterns. We defined oncology outreach as the provision of cancer care by a traveling oncologist outside of their primary HSA. We used hierarchical gamma regression models to examine the separate associations between patient receipt of oncology outreach and one-way patient travel times to chemotherapy, radiotherapy, and surgery. RESULTS: On average, 9,935 of 39,960 oncologists conducted annual outreach, where 57.8% traveled with low frequency (0-1 outreach visits/mo), 21.1% with medium frequency (1-3 outreach visits/mo), and 21.1% with high frequency (>3 outreach visits/mo). Oncologists provided surgery, radiotherapy, and chemotherapy to 51,715, 27,120, and 5,874 rural beneficiaries, respectively, of whom 2.5%, 6.9%, and 3.6% received oncology outreach. Rural patients who received oncology outreach traveled 16% (95% CI, 11 to 21) and 11% (95% CI, 9 to 13) less minutes to chemotherapy and radiotherapy than those who did not receive oncology outreach, corresponding to expected one-way savings of 15.9 (95% CI, 15.5 to 16.4) and 11.9 (95% CI, 11.7 to 12.2) minutes, respectively. CONCLUSION: Our study introduces a novel claims-based approach for tracking the nationwide traveling oncology workforce and supports oncology outreach as an effective means for improving rural access to cancer care.

Multiscale analysis of cancer service areas in the United States.

The purpose of delineating Cancer Service Areas (CSAs) is to define a reliable unit of analysis, more meaningful than geopolitical units such as states and counties, for examining geographic variations of the cancer care markets using geographic information systems (GIS). This study aims to provide a multiscale analysis of the U.S. cancer care markets based on the 2014-2015 Medicare claims of cancer-directed surgery, chemotherapy, and radiation. The CSAs are delineated by a scale-flexible network community detection algorithm automated in GIS so that the patient flows are maximized within CSAs and minimized between them. The multiscale CSAs include those comparable in size to those 4 census regions, 9 divisions, 50 states, and also 39 global optimal CSAs that generates the highest modularity value. The CSAs are more effective in capturing the U.S. cancer care markets because of its higher localization index, lower cross-border utilizations, and shorter travel time. The first two comparisons reveal that only a few regions or divisions are representative of the underlying cancer care markets. The last two comparisons find that among the 39 CSAs, 54% CSAs comprise multiple states anchored by cities near inner state borders, 28% are single-state CSAs, and 18% are sub-state CSAs. Their (in)consistencies across state borders or within each state shed new light on where the intervention of cancer care delivery or the adjustment of cancer care costs are needed to meet the challenges in the U.S. cancer care system. The findings could guide stakeholders to target public health policies for more effective coordination of cancer care in improving outcomes and reducing unnecessary costs.

Ectoderm-derived frontal bone mesenchymal stem cells promote traumatic brain injury recovery by alleviating neuroinflammation and glutamate excitotoxicity partially via FGF1.

BACKGROUND: Traumatic brain injury (TBI) leads to cell and tissue impairment, as well as functional deficits. Stem cells promote structural and functional recovery and thus are considered as a promising therapy for various nerve injuries. Here, we aimed to investigate the role of ectoderm-derived frontal bone mesenchymal stem cells (FbMSCs) in promoting cerebral repair and functional recovery in a murine TBI model. METHODS: A murine TBI model was established by injuring C57BL/6 N mice with moderate-controlled cortical impact to evaluate the extent of brain damage and behavioral deficits. Ectoderm-derived FbMSCs were isolated from the frontal bone and their characteristics were assessed using multiple differentiation assays, flow cytometry and microarray analysis. Brain repairment and functional recovery were analyzed at different days post-injury with or without FbMSC application. Behavioral tests were performed to assess learning and memory improvements. RNA sequencing analysis, immunofluorescence staining, and quantitative reverse-transcription polymerase chain reaction (qRT-PCR) were used to examine inflammation reaction and neural regeneration. In vitro co-culture analysis and quantification of glutamate transportation were carried out to explore the possible mechanism of neurogenesis and functional recovery promoted by FbMSCs. RESULTS: Ectoderm-derived FbMSCs showed fibroblast like morphology and osteogenic differentiation capacity. FbMSCs were CD105, CD29 positive and CD45, CD31 negative. Different from mesoderm-derived MSCs, FbMSCs expressed the ectoderm-specific transcription factor Tfap2ß. TBI mice showed impaired learning and memory deficits. Microglia and astrocyte activation, as well as neural damage, were significantly increased post-injury. FbMSC application ameliorated the behavioral deficits of TBI mice and promoted neural regeneration. RNA sequencing analysis showed that signal pathways related to inflammation decreased, whereas those related to neural activation increased. Immunofluorescence staining and qRT-PCR data revealed that microglial activation and astrocyte polarization to the A1 phenotype were suppressed by FbMSC application. In addition, FGF1 secreted from FbMSCs enhanced glutamate transportation by astrocytes and alleviated the cytotoxic effect of excessive glutamate on neurons. CONCLUSIONS: Ectoderm-derived FbMSC application significantly alleviated neuroinflammation, brain injury, and excitatory toxicity to neurons, improved cognition and behavioral deficits in TBI mice. Therefore, ectoderm-derived FbMSCs could be ideal therapeutic candidates for TBI which mostly affect cells from the same embryonic origins as FbMSCs.

Rural-Urban Differences in Breast Cancer Surgical Delays in Medicare Beneficiaries.

BACKGROUND: Delays between breast cancer diagnosis and surgery are associated with worsened survival. Delays are more common in urban-residing patients, although factors specific to surgical delays among rural and urban patients are not well understood. METHODS: We used a 100% sample of fee-for-service Medicare claims during 2007-2014 to identify 238,491 women diagnosed with early-stage breast cancer undergoing initial surgery and assessed whether they experienced biopsy-to-surgery intervals > 90 days. We employed multilevel regression to identify associations between delays and patient, regional, and surgeon characteristics, both in combined analyses and stratified by rurality of patient residence. RESULTS: Delays were more prevalent among urban patients (2.5%) than rural patients (1.9%). Rural patients with medium- or high-volume surgeons had lower odds of delay than patients with low-volume surgeons (odds ratio [OR] = 0.71, 95% confidence interval [CI] = 0.58-0.88; OR = 0.74, 95% CI = 0.61-0.90). Rural patients whose surgeon operated at ≥ 3 hospitals were more likely to experience delays (OR = 1.29, 95% CI = 1.01-1.64, Ref: 1 hospital). Patient driving times ≥ 1 h were associated with delays among urban patients only. Age, black race, Hispanic ethnicity, multimorbidity, and academic/specialty hospital status were associated with delays. CONCLUSIONS: Sociodemographic, geographic, surgeon, and facility factors have distinct associations with > 90-day delays to initial breast cancer surgery. Interventions to improve timeliness of breast cancer surgery may have disparate impacts on vulnerable populations by rural-urban status.

Disruption of hematopoiesis attenuates the osteogenic differentiation capacity of bone marrow stromal cells.

BACKGROUND: The homeostasis of mesenchymal stem cells (MSCs) is modulated by both their own intracellular molecules and extracellular milieu signals. Hematopoiesis in the bone marrow is maintained by niche cells, including MSCs, and it is indispensable for life. The role of MSCs in maintaining hematopoietic homeostasis has been fully elucidated. However, little is known about the mechanism by which hematopoietic cells reciprocally regulate niche cells. The present study aimed to explore the close relationship between MSCs and hematopoietic cells, which may be exploited for the development of new therapeutic strategies for related diseases. METHODS: In this study, we isolated cells from the offspring of Tie2Cre + and Ptenflox/flox mice. After cell isolation and culture, we investigated the effect of hematopoietic cells on MSCs using various methods, including flow cytometry, adipogenic and osteogenic differentiation analyses, quantitative PCR, western bloting, and microCT analysis. RESULTS: Our results showed that when the phosphatase and tensin homolog deleted on chromosome 10 (Pten) gene was half-deleted in hematopoietic cells, hematopoiesis and osteogenesis were normal in young mice; the frequency of erythroid progenitor cells in the bone marrow gradually decreased and osteogenesis in the femoral epiphysis weakened as the mice grew. The heterozygous loss of Pten in hematopoietic cells leads to the attenuation of osteogenic differentiation and enhanced adipogenic differentiation of MSCs in vitro. Co-culture with normal hematopoietic cells rescued the abnormal differentiation of MSCs, and in contrast, MSCs co-cultured with heterozygous null Pten hematopoietic cells showed abnormal differentiation activity. Co-culture with erythroid progenitor cells also revealed them to play an important role in MSC differentiation. CONCLUSION: Our data suggest that hematopoietic cells function as niche cells of MSCs to balance the differentiation activity of MSCs and may ultimately affect bone development.

Delineation of Cancer Service Areas Anchored by Major Cancer Centers in the United States.

Defining a reliable geographic unit pertaining to cancer care is essential in its assessment, planning, and management. This study aims to delineate and characterize the cancer service areas (CSA) accounting for the presence of major cancer centers in the United States. We used the Medicare enrollment and claims from January 1, 2014 to September 30, 2015 to build a spatial network from patients with cancer to cancer care facilities that provided inpatient and outpatient care of cancer-directed surgery, chemotherapy, and radiation. After excluding those without clinical care or outside of the United States, we identified 94 NCI-designated and other academic cancer centers from the members of the Association of American Cancer Institutes. By explicitly incorporating existing specialized cancer referral centers, we refined the spatially constrained Leiden method that accounted for spatial adjacency and other constraints to delineate coherent CSAs within which the service volumes were maximal but minimal between them. The derived 110 CSAs had a high mean localization index (LI; 0.83) with a narrow variability (SD = 0.10). The variation of LI across the CSAs was positively associated with population, median household income, and area size, and negatively with travel time. Averagely, patients traveled less and were more likely to receive cancer care within the CSAs anchored by cancer centers than their counterparts without cancer centers. We concluded that CSAs are effective in capturing the local cancer care markets in the United States. They can be used as reliable units for studying cancer care and informing more evidence-based policy. Significance: Using the most refined network community detection method, we can delineate CSAs in a more robust, systematic, and empirical manner that incorporates existing specialized cancer referral centers. The CSAs can be used as a reliable unit for studying cancer care and informing more evidence-based policy in the United States. The cross-walk tabulation of ZIP code areas, CSAs, and related programs for CSAs delineation are disseminated for public access.

Network Optimization Approach to Delineating Health Care Service Areas: Spatially Constrained Louvain and Leiden Algorithms.

Constructing service areas is an important task for evaluating geographic variation of health care markets. This study uses cancer care as an example to illustrate the methodology, with the nine-state Northeast Region of the U.S. as the study area. Two recent algorithms of network community detection are implemented to account for additional constraints such as spatial connectivity and threshold region size. The refined methods are termed "spatially-constrained Louvain (ScLouvain)" and "spatially-constrained Leiden (ScLeiden)" algorithms, corresponding to their predecessors Louvain and Leiden algorithms, respectively. Both are network optimization methods that maximize flows within delineated communities while minimizing inter-community flows. The service areas derived by the methods, termed "Cancer Service Areas (CSAs)", are more favorable than the commonly used comparable unit, Hospital Referral Regions (HRRs) for evaluating cancer-specific variation in care. Between the two, the ScLeiden performs better than ScLouvain in modularity, localization index and computational efficiency, and thus is recommended as an effective and efficient approach for defining functional regions.

Spatial Behavior of Cancer Care Utilization in Distance Decay in the Northeast Region of the U.S.

PURPOSE: Spatial behavior of patients in utilizing health care reflects their travel burden or mobility, accessibility for medical service, and subsequently outcomes from treatment. This paper derives the best-fitting distance decay function to capture the spatial behaviors of cancer patients in the Northeast region of the U.S., and examines and explains the spatial variability of such behaviors across sub-regions. PRINCIPAL RESULTS: (1) 46.8%, 85.5%, and 99.6% of cancer care received was within a driving time of 30, 60 and 180 minutes, respectively. (2) The exponential distance decay function is the best in capturing the travel behavior of cancer patients in the region and across most sub-regions. (3) The friction coefficient in the distance decay function is negatively correlated with the mean travel time. (4) The best-fitting function forms are associated with network structures. (5) The variation of the friction coefficient across sub-regions is related to factors such as urbanicity, economic development level, and market competition intensity. MAJOR CONCLUSIONS: The distance decay function offers an analytic metric to capture a full spectrum of travel behavior, and thus a more comprehensive measure than average travel time. Examining the geographic variation of travel behavior needs a reliable analysis unit such as organically defined "cancer service areas", which capture relevant health care market structure and thus are more meaningful than commonly-used geopolitical or census area units.

Identification of a novel tetracycline resistance gene, tet(63), located on a multiresistance plasmid from Staphylococcus aureus.

OBJECTIVES: To identify and characterize a novel tetracycline resistance gene on a multiresistance plasmid from Staphylococcus aureus SA01 of chicken origin. METHODS: MICs were determined by broth microdilution according to CLSI recommendations. The whole genome sequence of S. aureus SA01 was determined via Illumina HiSeq and Oxford Nanopore platforms followed by a hybrid assembly. The new tet gene was cloned and expressed in S. aureus. The functionality of the corresponding protein as an efflux pump was tested by efflux pump inhibition assays. RESULTS: A novel tetracycline resistance gene, tet(63), was identified on a plasmid in S. aureus SA01. The cloned tet(63) gene was functionally expressed in S. aureus and shown to confer resistance to tetracycline and doxycycline, and a slightly elevated MIC of minocycline. The tet(63) gene encodes a 459 amino acid efflux protein of the major facilitator superfamily that consists of 14 predicted transmembrane helices. The results of efflux pump inhibitor assays confirmed the function of Tet(63) as an efflux protein. The deduced amino acid sequence of the Tet(63) protein exhibited 73.0% identity to the tetracycline efflux protein Tet(K). The plasmid pSA01-tet, on which tet(63) was located, had a size of 25664 bp and also carried the resistance genes aadD, aacA-aphD and erm(C). CONCLUSIONS: A novel tetracycline resistance gene, tet(63), was identified in S. aureus. Its location on a multiresistance plasmid might support the co-selection of tet(63) under the selective pressure imposed by the use of macrolides, lincosamides and aminoglycosides.

Automated delineation of cancer service areas in northeast region of the United States: A network optimization approach.

OBJECTIVE: Derivation of service areas is an important methodology for evaluating healthcare variation, which can be refined to more robust, condition-specific, and empirically-based automated regions, using cancer service areas as an exemplar. DATA SOURCES/STUDY SETTING: Medicare claims (2014-2015) for the nine-state Northeast region were used to develop a ZIP-code-level origin-destination matrix for cancer services (surgery, chemotherapy, and radiation). This population-based study followed a utilization-based approach to delineate cancer service areas (CSAs) to develop and test an improved methodology for small area analyses. DATA COLLECTION/EXTRACTION METHODS: Using the cancer service origin-destination matrix, we estimated travel time between all ZIP-code pairs, and applied a community detection method to delineate CSAs, which were tested for localization, modularity, and compactness, and compared to existing service areas. PRINCIPAL FINDINGS: Delineating 17 CSAs in the Northeast yielded optimal parameters, with a mean localization index (LI) of 0.88 (min: 0.60, max: 0.98), compared to the 43 Hospital Referral Regions (HRR) in the region (mean LI: 0.68; min: 0.18, max: 0.97). Modularity and compactness were similarly improved for CSAs vs. HRRs. CONCLUSIONS: Deriving cancer-specific service areas with an automated algorithm that uses empirical and network methods showed improved performance on geographic measures compared to more general, hospital-based service areas.

miR-155 Regulates the Proliferation of Glioma Cells Through PI3K/AKT Signaling.

Objective: Micro-RNA plays a critical role in the pathological process of gliomas. Previous research showed that the level of miR-155 was significantly increased in many cancers, including gliomas. However, the mechanism of glioma is still unknown. Method: To investigate the regulatory function of miR-155 on glioma U87-MG cells and its effects on related signaling pathways. After transfection of miR-155 mimic and inhibitor, the level of miR-155 were applied to detect cell proliferation, apoptosis, senescence index, invasive ability and cell migration at different time points (0, 24, 24 h, respectively) by CCK8 assay, flow cytometry, ß-galactosidase (ß-gal) staining, transwell and scratch test, respectively. The effect of miR-155 on PI3K/AKT signal pathway was observed at meantime. Results: Compared with the control group, after miR-155 mimic transfection, U87-MG cell viability, cell migration rate and invasiveness were increased, while apoptosis and senescence were significantly decreased, which was the opposite on miR-155 inhibitor transfection. The phosphorylation levels of miR-155, PI3K, AKT, PI3K, and AKT in U87-MG cells intervened with miR-155 mimic also increased significantly, while the levels of PTEN, Caspase-3, Caspase-9 mRNA, and protein declined significantly, with statistically significant difference. Meanwhile, compared with the control group, miR-155 inhibitor group were on the contrary. Conclusion: The study indicated that miR-155 take charge a key function in regulating the proliferation, migration, and invasion of glioma U87-MG cells through PI3K/AKT signaling pathway, and has anti-glioma effects by inhibition of miR-155, which provided ideas for further clinical treatment of glioma patients.

Radiofrequency radiation at 2.856 GHz does not affect key cellular endpoints in neuron-like PC12 cells.

To investigate the potential cytotoxicity of radiofrequency (RF) radiation on central nervous system, rat pheochromocytoma (PC12) cells were exposed to 2.856 GHz RF radiation at a specific absorption rate (SAR) of 4 W/kg for 8 h a day for 2 days in 35 mm Petri dishes. During exposure, the real-time variation of the culture medium temperature was monitored in the first hour. Reactive oxygen species (ROS) production, intracellular Ca2+ concentration, and cell apoptosis rate were assessed immediately after exposure by flow cytometry. The results showed that the medium temperature raised about 0.93 °C, but no significant changes were observed in apoptosis, ROS levels or intracellular Ca2+ concentration after treatment. Although several studies suggested that RF radiation does indeed cause neurological effects, this study presented inconsistent results, indicating that 2.856 GHz RF radiation exposure at a SAR of 4 W/kg does not have a dramatic impact on PC12 cells, and suggests the need for further investigation on the key cellular endpoints of other nerve cells after exposure to RF radiation.

Microwave radiation leading to shrinkage of dendritic spines in hippocampal neurons mediated by SNK-SPAR pathway.

The popularization of microwave raised concerns about its influence on health including cognitive function which is associated greatly with dendritic spines plasticity. SNK-SPAR is a molecular pathway for neuronal homeostatic plasticity during chronically elevated activity. In this study, Wistar rats were exposed to microwaves (30 mW/cm2 for 6 min, 3 times/week for 6 weeks). Spatial learning and memory function, distribution of dendritic spines, ultrastructure of the neurons and their dendritic spines in hippocampus as well as the related critical molecules of SNK-SPAR pathway were examined at different time points after microwave exposure. There was deficiency in spatial learning and memory in rats, loss of spines in granule cells and shrinkage of mature spines in pyramidal cells, accompanied with alteration of ultrastructure of hippocampus neurons. After exposure to 30 mW/cm2 microwave radiation, the up-regulated SNK induced decrease of SPAR and PSD-95, which was thought to cause the changes mentioned above. In conclusion, the microwave radiation led to shrinkage and even loss of dendritic spines in hippocampus by SNK-SPAR pathway, resulting in the cognitive impairments.

Non-linear optical imaging and quantitative analysis of the pathological changes in normal and carcinomatous human colorectal muscularis.

Non-linear optical (NLO) imaging based on two-photon excitation (2PE) and second harmonic generation (SHG) has been widely used to image microstructures of biomedical specimens over the last two decades. We employed NLO imaging technology to investigate the histology of normal and carcinomatous human colorectal muscularis in transverse and longitudinal views. Results show there are different patterns of pathological changes of muscularis in tissue structure and cell morphology from both views. The NLO imaging provides identical histological information as the H&E images but requires neither stain nor tissue processing. Our study indicates that NLO imaging technology shows more detailed microstructure, which is a critical complementary tool in pathological diagnosis of colorectal tumours. It suggests that NLO imaging could be a very important diagnostic tool to help pathologists realise the real time early detection of human colorectal tumours in the foreseeable future.

Identification of a Novel Rat NR2B Subunit Gene Promoter Region Variant and Its Association with Microwave-Induced Neuron Impairment.

Microwave radiation has been implicated in cognitive dysfunction and neuronal injury in animal models and in human investigations; however, the mechanism of these effects is unclear. In this study, single nucleotide polymorphism (SNP) sites in the rat GRIN2B promoter region were screened. The associations of these SNPs with microwave-induced rat brain dysfunction and with rat pheochromocytoma-12 (PC12) cell function were investigated. Wistar rats (n = 160) were exposed to microwave radiation (30 mW/cm(2) for 5 min/day, 5 days/week, over a period of 2 months). Screening of the GRIN2B promoter region revealed a stable C-to-T variant at nucleotide position -217 that was not induced by microwave exposure. The learning and memory ability, amino acid contents in the hippocampus and cerebrospinal fluid, and NR2B expression were then investigated in the different genotypes. Following microwave exposure, NR2B protein expression decreased, while the Glu contents in the hippocampus and CSF increased, and memory impairment was observed in the TT genotype but not the CC and CT genotypes. In PC12 cells, the effects of the T allele were more pronounced than those of the C allele on transcription factor binding ability, transcriptional activity, NR2B mRNA, and protein expression. These effects may be related to the detrimental role of the T allele and the protective role of the C allele in rat brain function and PC12 cells exposed to microwave radiation.

Effects of pulsed 2.856 GHz microwave exposure on BM-MSCs isolated from C57BL/6 mice.

The increasing use of microwave devices over recent years has meant the bioeffects of microwave exposure have been widely investigated and reported. However the exact biological fate of bone marrow MSCs (BM-MSCs) after microwave radiation remains unknown. In this study, the potential cytotoxicity on MSC proliferation, apoptosis, cell cycle, and in vitro differentiation were assayed following 2.856 GHz microwave exposure at a specific absorption rate (SAR) of 4 W/kg. Importantly, our findings indicated no significant changes in cell viability, cell division and apoptosis after microwave treatment. Furthermore, we detected no significant effects on the differentiation ability of these cells in vitro, with the exception of reduction in mRNA expression levels of osteopontin (OPN) and osteocalcin (OCN). These findings suggest that microwave treatment at a SAR of 4 W/kg has undefined adverse effects on BM-MSCs. However, the reduced-expression of proteins related to osteogenic differentiation suggests that microwave can the influence at the mRNA expression genetic level.

Neuroprotective effects of dietary supplement Kang-fu-ling against high-power microwave through antioxidant action.

Kang-fu-ling (KFL) is a polybotanical dietary supplement with antioxidant properties. This study aimed to evaluate the potential protective effects of KFL on cognitive deficit induced by high-power microwave (HPM) and the underlying mechanism for this neuroprotection. The electron spin resonance technique was employed to evaluate the free radical scavenging activity of KFL in vitro and KFL exhibited scavenging hydroxyl radical activity. KFL at doses of 0.75, 1.5 and 3 g kg(-1) and vehicle were administered orally once daily for 14 days to male Wistar rats after being exposed to 30 mW cm(-2) HPM for 15 minutes. KFL reversed HPM-induced memory loss and the histopathological changes in hippocampus of rats. In addition, KFL displayed a protective effect against HPM-induced oxidative stress and activated the nuclear factor-E2-related factor 2 (Nrf2) and its target genes in the hippocampus of rats. The Nrf2-antioxidant response element (ARE) signaling pathway may be involved in the neuroprotective effects of KFL against HPM-induced oxidative stress. In summary, the dietary supplement KFL is a promising natural complex, which ameliorates oxidative stress, with neuroprotective effects against HPM.

Wushen, a food mixture containing 55 different natural ingredients, inhibits S180 tumor growth in vivo.

As cancer has become a worldwide threat to human life and health, developing a safe and effective tumor-inhibiting agent is presently a major scientific challenge. In this study, a food mixture produced from 55 different natural ingredients called wushen was fed to S180 tumor-bearing mice, and the antitumor effects were investigated in vivo. Kunming mice were implanted subcutaneously in the armpit with murine sarcoma S180 cells to construct the S180 tumor-bearing mouse model. The mice were randomly divided into three groups: control, wushen and 5-fluorouracil (5-Fu). 5-Fu was used as the positive drug treatment to confirm the reliability of the model. The food intake, antitumor rate, and spleen and thymus indices were recorded. Tumor histopathology was conducted using hematoxylin and eosin (H&E) staining. The catalase, glutathione peroxidase, and superoxide dismutase activities and the malondialdehyde concentration were measured to evaluate the antioxidative effects of the treatments. The antitumor rate of the mice fed wushen was 48.52%. Wushen-treated mice exhibited alterations in antioxidative enzyme activity and reduced liver lipid peroxidation. The results demonstrated that wushen has antitumor effects on S180 tumor-bearing mice in vivo, and the underlying mechanism is partially due to its antioxidant activity. Wushen, which contains various natural products, can be eaten directly and may be beneficial to human health.