The platelet storage lesion, what are we working for?

BACKGROUND: Platelet concentrate (PC) transfusions are crucial in prevention and treatment of bleeding in infection, surgery, leukemia, and thrombocytopenia patients. Although the technology for platelet preparation and storage has evolved over the decades, there are still challenges in the demand for platelets in blood banks because the platelet shelf life is limited to 5 days due to bacterial contamination and platelet storage lesions (PSLs) at 20-24°C under constant horizontal agitation. In addition, the relations between some adverse effects of platelet transfusions and PSLs have also been considered. Therefore, understanding the mechanisms of PSLs is conducive to obtaining high quality platelets and facilitating safe and effective platelet transfusions. OBJECTIVE: This review summarizes developments in mechanistic research of PSLs and their relationship with clinical practice, providing insights for future research. METHODS: Authors conducted a search on PubMed and Web of Science using the professional terms "PSL" and "platelet transfusion." The obtained literature was then roughly categorized based on their research content. Similar studies were grouped into the same sections, and further searches were conducted based on the keywords of each section. RESULTS: Different studies have explored PSLs from various perspectives, including changes in platelet morphology, surface molecules, biological response modifiers (BMRs), metabolism, and proteins and RNA, in an attempt to monitor PSLs and identify intervention targets that could alleviate PSLs. Moreover, novel platelet storage conditions, including platelet additive solutions (PAS) and reconsidered cold storage methods, are explored. There are two approaches to obtaining high-quality platelets. One approach simulates the in vivo environment to maintain platelet activity, while the other keeps platelets at a low activity level in vitro under low temperatures. CONCLUSION: Understanding PSLs helps us identify good intervention targets and assess the therapeutic effects of different PSLs stages for different patients.

Rice bran arabinoxylan compound as a natural product for cancer treatment - an evidence-based assessment of the effects and mechanisms.

CONTEXT: Rice bran arabinoxylan compound (RBAC) is a natural immunomodulator with anticancer properties. OBJECTIVE: This study critically evaluates the available evidence on the biological pathways of RBAC and its effects on cancer treatment. METHODS: This secondary analysis of a scoping review includes studies evaluating the mechanisms of RBAC on healthy or malignant cells, animal models, or humans for cancer prevention or treatment. Data from randomized controlled trials on survival and quality of life outcomes were subjectd to meta analysis. RESULTS: The evidence synthesis was based on 38 articles. RBAC exhibited antitumor properties by promoting apoptosis and restoring immune function in cancer patients to enhance inflammatory and cytotoxic responses to block tumorigenesis. RBAC works synergistically with chemotherapeutic agents by upregulating drug transport. In a clinical trial, combining RBAC with chemoembolization in treating liver cancer showed improved response, reduced recurrence rates, and prolonged survival. RBAC also augments the endogenous antioxidant system to prevent oxidative stress and protect against radiation side effects. In addition, RBAC has chemoprotective effects. Animals and humans have exhibited reduced toxicity and side effects from chemotherapy. Meta analysis indicates that RBAC treatment increases the survival odds by 4.02-times (95% CI: 1.67, 9.69) in the first year and 2.89-times (95% CI: 1.56, 5.35) in the second year. CONCLUSION: RBAC is a natural product with immense potential in cancer treatment. Additional research is needed to characterize, quantify, and standardize the active ingredients in RBAC responsible for the anticancer effects. More well-designed, large-scale clinical trials are required to substantiate the treatment efficacies further.

Review of Dual Biologics in Specialty Pharmacy Practice.

OBJECTIVE: To describe and review the published evidence on use of multiple biologics within specialty pharmacy practice. DATA SOURCES: A search of PubMed and Embase was conducted from October 2021 through September 2022. Keywords included biologics for immune-mediated conditions along with the terms "dual," "add-on," and "combination." STUDY SELECTION AND DATA EXTRACTION: All human studies in the English language were considered. Published abstracts, case reports, case series, randomized controlled trials, systematic reviews, and meta-analyses were included. DATA SYNTHESIS: Although evidence is limited, there are published meta-analyses of combined biologic use within gastroenterology and rheumatology. There are also numerous case reports within dermatology. Clinical trials of dual biologics for severe rheumatologic conditions and inflammatory bowel disease are in progress. Existing evidence for use in pulmonology and allergy suggest dual biologic therapy can be safe and effective, but data are limited. Literature describing use of monoclonal antibodies for other overlapping conditions is lacking. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: This article reviews the evidence describing combination biologic use and outlines remaining knowledge gaps. It also describes the essential role that specialty pharmacists play in managing therapeutic mAbs. CONCLUSIONS: High-quality evidence describing combination biologic use is limited and long-term safety data are lacking. Pharmacists should utilize their specialized training to assess appropriateness of therapy, provide patient counseling and monitor for safety and efficacy.

Effects of selenium deficiency on biological results of X-ray and carbon-ion beam irradiation in mice.

The impact of radiation-induced hydrogen peroxide (H2O2) on the biological effects of X-rays and carbon-ion beams was investigated using a selenium-deficient (SeD) mouse model. Selenium is the active center of glutathione peroxidase (GSH-Px), and SeD mice lack the ability to degrade H2O2. Male and female SeD mice were prepared by feeding a torula yeast-based SeD diet and ultrapure water. Thirty-day survival rates after whole-body irradiation, radiation-induced leg contracture, and MRI-based redox imaging of the brain were assessed and compared between SeD and normal mice. Thirty-day lethality after whole-body 5.6 Gy irradiation with X-rays or carbon-ion beams was higher in the SeD mice than in the normal mice, while SeD did not give the notable difference between X-rays and carbon-ion beams. SeD also did not affect the maximum leg contracture level after irradiation with carbon-ion beams, but delayed the leg contraction rate. In addition, no marked effects of SeD were observed on variations in the redox status of the brain after irradiation. Collectively, the present results indicate that SeD slightly altered the biological effects of X-rays and/or carbon-ion beams. GSH-Px processes endogenous H2O2 generated through mitochondrial respiration, but does not have the capacity to degrade H2O2 produced by irradiation.

The surfactant Dioctyl Sodium Sulfosuccinate (DOSS) exposure causes adverse effects in embryos and adults of zebrafish (Danio rerio).

Dioctyl Sodium Sulfosuccinate (DOSS, CAS 577-11-7) is a chemical emulsifying surfactant that is widely used in the food and the cosmetic industry, and it is also the major component of the crude oil chemical dispersant Corexit™. Despite of its wide use, the studies related to its negative effect have been evaluated mainly in marine environments showing that DOSS is highly bioactive, extremely low volatile, and potential to persist in the environment longer than other dispersant components. Up to date, there is no available information of DOSS concentration in freshwater environments, little is known about its downstream fate after excretion and its effect on freshwater organisms. The objective of this study was to evaluate the effect of DOSS at different concentrations in embryos and adults of zebrafish Danio rerio in an acute-static bioassays of 96 h. The median lethal concentration in embryos was 33.3 mg/L. Malformations started to be observed at 10 mg/L. In adults, the gene expression analysis in gill tissues showed a deregulation in genes associated with the antioxidant system and the nucleotide excision repair mechanism. Additionally, Micronuclei (DNA damage) in erythrocytes, and fat degeneration in liver, hypertrophy and hyperplasia in gills, and hyaline drops in kidney tissues were also observed. In conclusion, the concentrations of DOSS evaluated here would be of health relevance to fish based on morphological alterations in embryos and changes in the gene expression profile, DNA damage and tissue impairment in adults.

ß-glucan, "the knight of health sector": critical insights on physiochemical heterogeneities, action mechanisms and health implications.

ß-glucans, the class of biological response modifier has unceasing attention, not only for its immune stimulating but also for its role as prebiotics, modulator of physiological events etc. and is widely used in the treatment of cancer, diabetes, gastrointestinal disorders, cardiovascular diseases etc. However, ß-glucan with different physiochemical properties is found to have discrete clinical functions and thus careful selection of the types of ß-glucan plays pivotal role in providing significant and expected clinical outcome. Herein this review, we presented the factors responsible for diverse functional properties of ß-glucan, their distinct mode of actions in regulating human health etc. Further, clinical aspects of different ß-glucans toward the management of wound care, metabolic dysbiosis, fatty liver disorders and endurance training associated energy metabolism were compiled and exhibited in detail.

Potential of Magnetic Hyperthermia to Stimulate Localized Immune Activation.

Magnetic hyperthermia (MH) harnesses the heat-releasing properties of superparamagnetic iron oxide nanoparticles (SPIONs) and has potential to stimulate immune activation in the tumor microenvironment whilst sparing surrounding normal tissues. To assess feasibility of localized MH in vivo, SPIONs are injected intratumorally and their fate tracked by Zirconium-89-positron emission tomography, histological analysis, and electron microscopy. Experiments show that an average of 49% (21-87%, n = 9) of SPIONs are retained within the tumor or immediately surrounding tissue. In situ heating is subsequently generated by exposure to an externally applied alternating magnetic field and monitored by thermal imaging. Tissue response to hyperthermia, measured by immunohistochemical image analysis, reveals specific and localized heat-shock protein expression following treatment. Tumor growth inhibition is also observed. To evaluate the potential effects of MH on the immune landscape, flow cytometry is used to characterize immune cells from excised tumors and draining lymph nodes. Results show an influx of activated cytotoxic T cells, alongside an increase in proliferating regulatory T cells, following treatment. Complementary changes are found in draining lymph nodes. In conclusion, results indicate that biologically reactive MH is achievable in vivo and can generate localized changes consistent with an anti-tumor immune response.

Transcriptomics and Metabolomics Revealed the Biological Response of Chlorella pyrenoidesa to Single and Repeated Exposures of AgNPs at Different Concentrations.

Increased release of engineered nanoparticles (ENPs) from widely used commercial products has threatened environmental health and safety, particularly the repeated exposures to ENPs with relatively low concentration. Herein, we studied the response of Chlorella pyrenoidesa (C. pyrenoidesa) to single and repeated exposures to silver nanoparticles (AgNPs). Repeated exposures to AgNPs promoted chlorophyll a and carotenoid production, and increased silver accumulation, thus enhancing the risk of AgNPs entering the food chain. Notably, the extracellular polymeric substances (EPS) content of the 1-AgNPs and 3-AgNPs groups were dramatically increased by 119.1% and 151.5%, respectively. We found that C. pyrenoidesa cells exposed to AgNPs had several significant alterations in metabolic process and cellular transcription. Most of the genes and metabolites are altered in a dose-dependent manner. Compared with the control group, single exposure had more differential genes and metabolites than repeated exposures. 562, 1341, 4014, 227, 483, and 2409 unigenes were differentially expressed by 1-0.5-AgNPs, 1-5-AgNPs, 1-10-AgNPs, 3-0.5-AgNPs, 3-5-AgNPs, and 3-10-AgNPs treatment groups compared with the control. Metabolomic analyses revealed that AgNPs altered the levels of sugars and amino acids, suggesting that AgNPs reprogrammed carbon/nitrogen metabolism. The changes of genes related to carbohydrate and amino acid metabolism, such as citrate synthase (CS), isocitrate dehydrogenase (IDH1), and malate dehydrogenase (MDH), further supported these results. These findings elucidated the mechanism of biological responses to repeated exposures to AgNPs, providing a new perspective on the risk assessment of nanomaterials.

Impacts and tolerance responses of Coprinus comatus and Pleurotus cornucopiae on cadmium contaminated soil.

Large amounts of cadmium (Cd) have been discharged into soil with the rapid development of industry. In this study, we revealed the impacts of Coprinus comatus (C. comatus) and Pleurotus cornucopiae (P. cornucopiae) on soil and the tolerance responses of macrofungi in the presence of Cd by the analysis of soil biochemical properties and macrofungi growth indexes. Results showed that with the cultivation of C. comatus and P. cornucopiae, the HOAc-extractable Cd in soil individually reduced by 9.53% and 11.35%, the activities of soil urease, acid phosphatase, dehydrogenase, and Fluorescein diacetate (FDA) hydrolysis increased by 18.11-101.45%, 8.39-18.24%, 9.37-55.50% and 28.94-41.92%, respectively. Meanwhile, different soil bacterial communities were observed with various macrofungi cultivations. Also, Cd accumulation significantly enhanced the macrofungi antioxidant enzyme activities, which increased by 24.10-45.43%, 30.11-61.53% and 7.03-26.81% for catalase (CAT), peroxidase (POD), and superoxide dismutase (SOD) activities in the macrofungi, respectively. Moreover, the enhanced macrofungi endophytic bacterial diversities with Cd existence was firstly observed in the present experiment. These findings revealed the possible Cd resistance mechanisms in macrofungi, suggesting C. comatus and P. cornucopiae were promising ameliorators for Cd contaminated soil.

Biomonitoring the effects of urban-stream waters on the health status of pale chub (Zacco platypus): A comparative analysis of biological indexes and biomarker levels.

The objective of this study was to biomonitor the effects of potential environmental pollutants in urban-stream waters, on fish health. Pale chub (Zacco platypus), a dominant species in the Korea urban stream waters, was chosen and biomonitoring indicators for the different spatial characteristics were tailored in an urban watershed. Biological responses including biotic-somatic index as well as gonadal development phase and plasma steroids levels, and the biochemical responses, ethoxyresorufin-o-deethylase (EROD) and acetylcholinesterase (AChE) activities, were measured. No significant difference was observed in the length-weight relationship between the up-stream waters and the down-stream waters. However, changes in the gonad-somatic index (GSI) levels, plasma 17ß-estradiol (E2) levels, and mature oocyte frequencies in the female fish collected during the spawning season were observed in the down-stream waters at each monitoring site. Moreover, intersex condition (testis-ova) in the male fish in down-stream waters was recorded, even if it was just one fish. Although no significant difference was observed in the EROD and AChE activities between the up-stream waters and the down-stream waters, changes in the reproductive biomarker levels, including the GSI levels, plasma E2 levels, and gonadal maturation, lead to variable biomonitoring endpoints between the spatial different sites. These results imply that exposure to the down-stream waters can cause reproductive impairment in wild Z. platypus, individual variability in the biological responses further indicate the reproductive health was affected more by the down-stream waters than the up-stream waters. The finding from this study can provide the biomonitoring endpoint on the wild fish health in urban watershed that is crucial to the early risk assessment of its biological impacts. More multi-biomarkers studies reflecting the variation in the biological organization of wild fish and, therefore, the effects of urban-stream waters in the fish health are warranted.

Multifactorial Background for a Low Biological Response to Antiplatelet Agents Used in Stroke Prevention.

Effective platelet inhibition is the main goal of the antiplatelet therapy recommended as a standard treatment in the secondary prevention of non-embolic ischemic stroke. Acetylsalicylic acid (aspirin) and clopidogrel are commonly used for this purpose worldwide. A low biological response to antiplatelet agents is a phenomenon that significantly reduces the therapeutic and protective properties of the therapy. The mechanisms leading to high on-treatment platelet reactivity are still unclear and remain multifactorial. The aim of the current review is to establish the background of resistance to antiplatelet agents commonly used in the secondary prevention of ischemic stroke and to explain the possible mechanisms. The most important factors influencing the incidence of a low biological response were demonstrated. The similarities and the differences in resistance to both drugs are emphasized, which may facilitate the selection of the appropriate antiplatelet agent in relation to specific clinical conditions and comorbidities. Despite the lack of indications for the routine assessment of platelet reactivity in stroke subjects, this should be performed in selected patients from the high-risk group. Increasing the detectability of low antiaggregant responders, in light of its negative impact on the prognosis and clinical outcomes, can contribute to a more individualized approach and modification of the antiplatelet therapy to maximize the therapeutic effect in the secondary prevention of stroke.

Early biological responses in ocular tissue after SMILE and LASIK surgery.

We studied the early protein profile in the ocular tissue extracted after LASIK and SMILE surgery. SMILE and LASIK was performed in contralateral eyes and stromal tissue samples were collected from 10 eyes of 5 donors. The stromal tissue samples were analyzed using label free quantification approach and ITRAQ labelling approach in LC-MS/MS. Combined functional analysis revealed many differentially expressed proteins which were involved in important biological processes. About 117 unique differentially expressed proteins were identified using two different proteomic approaches. Collagens, proteoglycans, corneal crystallins were enriched and showed differential expression in SMILE and LASIK as compared to the non-surgical control. Apart from these, 14-3-3 class of proteins, Lysozyme (LYZ), Macrophage Migratory Inhibitory Factor protein (MIF), Pigment Epithelial Derived Factor (PEDF) were differentially expressed when compared between LASIK and SMILE. Peroxiredoxin 1 (PRDX1) expression was found to be reduced in LASIK as compared to SMILE. The expression of Lysozyme C and Macrophage Migratory Inhibitory Factor inflammatory response was found to be less in SMILE as compared to LASIK. Western blot validation of specific markers such as Collagen IV (COL4), Keratocan (KERA), Lumican (LUM), Aldehyde dehydrogenase 3 A1 (ALDH3A1), Lysozyme C (LYZC) confirmed the differences in the protein levels observed in SMILE and LASIK operated tissues as compared to non-surgical controls. In conclusion, this study revealed the early molecular changes occurring in the cornea resulting from these two surgical procedures which may have implications on managing post-operative complications.

Understanding Nanomedicine Size and Biological Response Dependency: What Is the Relevance of Previous Relationships Established on Only Batch-Mode DLS-Measured Sizes?

PURPOSE: Most relationships between size and nanomedicine performance and safety were established before the early 2010s' when batch-mode dynamic light scattering (batch-mode DLS) was the only easy size measurement method for colloids available. They are basis for the rational design of nanomedicines, but misunderstood contrasting results are reported. This work aimed to investigate whether these relationships can be used with confidence knowing that batch-mode DLS can be tricky when measuring sizes of polydisperse systems. METHODS: A polydisperse dispersion of polymer nanoparticles ranging from 100 to 465 nm was synthesized. The particles were separated in 4 fractions by successive centrifugations. The capacity of each fraction and parent dispersion to activate the complement system was evaluated by Crossed immuno-electrophoresis. RESULTS: Each fraction was a population of particles with a distinct size. It showed a different capacity to activate the complement system. Particles of the fractions showing the strongest capacity to activate the complement systems had a different size evaluated by batch-mode DLS then that of the parent particles. CONCLUSION: Particles activating the complement system in the parent dispersion were not those that were detected by batch-mode DLS while measuring its size. This work pointed out that previously established relationships between nanomedicine size and their biological response should be taken with caution if sizes were only measured by batch-mode DLS.

Assessment of the immobilization effectiveness of several amendments on a cadmium-contaminated soil using Eisenia fetida.

Proper protocols for assessing the remediation effectiveness of contaminated soils are an important part of remediation projects. In the present study, the residual immobilization effectiveness of hydrated lime (L), hydroxyapatite (H), biochar (B) and organic fertilizer (F) alone and in combination was assessed by Eisenia fetida. The results showed that the application of amendments had no significant effect on the death rate and average fresh weight loss of earthworms. The earthworm Cd concentration increased with prolonged exposure time, however, the significant immobilization efficacy of amendments observed on the 7th day nearly disappeared after 28 days of exposure. The immobilization efficiencies, estimated by the earthworms internal Cd concentration, of L, H and B on the 7th day were 38.6%, 37.8% and 20.7%, respectively. These values decreased to 4.9%, 19.8% and 15.1%, respectively, on the 28th day. The detoxification effect of amendments was confirmed by the Cd subcellular fractionation in earthworms with lower proportions of Cd distributed in the metal-sensitive fractions in L, H and B treatments. The level of oxidative stress response of earthworms increased with exposure duration and amendments alleviated the oxidative damage induced by Cd to the earthworms. In addition, the pH and CaCl2-Cd in soils were both increased due to earthworm life activities and gut-related ingestion. In summary, the assessment of immobilization effectiveness of heavy metal-contaminated soils using Eisenia fetida was time-dependent. The immobilization efficacy of L and H performed better than B and F on the 7th day, while H and B performed better than L and F on the 28th day. Accordingly, the short-term earthworm exposure experiment (7 days) was recommended to be an alternative approach to time-consuming plant bioassays in assessment of reduced phytoavailability in chemical immobilization remediation. But the impact of earthworms on the immobilization effect of amendments needs to be considered in practical remediation.

Ocean acidification refugia in variable environments.

Climate change refugia in the terrestrial biosphere are areas where species are protected from global environmental change and arise from natural heterogeneity in landscapes and climate. Within the marine realm, ocean acidification, or the global decline in seawater pH, remains a pervasive threat to organisms and ecosystems. Natural variability in seawater carbon dioxide (CO2 ) chemistry, however, presents an opportunity to identify ocean acidification refugia (OAR) for marine species. Here, we review the literature to examine the impacts of variable CO2 chemistry on biological responses to ocean acidification and develop a framework of definitions and criteria that connects current OAR research to management goals. Under the concept of managing vulnerability, the most likely mechanisms by which OAR can mitigate ocean acidification impacts are by reducing exposure to harmful conditions or enhancing adaptive capacity. While local management options, such as OAR, show some promise, they present unique challenges, and reducing global anthropogenic CO2 emissions must remain a priority.

Biological-Profiling-Based Systematic Analysis of Rhizoma Coptidis from Different Growing Regions and Its Anticholesterol Biosynthesis Activity on HepG2 Cells.

Rhizoma Coptidis is a widely cultivated traditional Chinese herb. Although the chemical profiles of Rhizoma Coptidis have been established previously, the biological profiling of Rhizoma Coptidis has not been conducted yet. In this study, we collected Rhizoma Coptidis varieties from four distinct growing regions and performed genome-wide biological response fingerprinting (BioReF) on HepG2 cells using a gene expression array. Similar biological pathways were affected by extracts of all four Rhizoma Coptidis varieties but not by their analogue, Mahoniae Caulis. Among these pathways, the terpenoid backbone biosynthesis pathway was highly enriched, and six genes in the mevalonate (MVA) pathway were all down-regulated. However, the expression, maturation, as well as the specific DNA binding capacity of their coordinate transcription factor, sterol response element binding protein 2 (SREBP2), was not affected by Rhizoma Coptidis extract (RCE) or its typical active alkaloid berberine. Cellular cholesterol content tests further verified the cholesterol-lowering function of RCE in vitro, which supplements evidence for the use of Rhizoma Coptidis in hyperlipidemia treatment. This is the first described example of evaluating the quality of Rhizoma Coptidis with BioReF and a good demonstration of using BioReF to uncover the mechanisms of herbs at a systematic level.

Intestinal damage, neurotoxicity and biochemical responses caused by tris (2-chloroethyl) phosphate and tricresyl phosphate on earthworm.

Organophosphate esters (OPEs) draw growing concern about characterizing the potential risk on environmental health due to its wide usage and distribution. Two typical types of organophosphate esters (OPEs): tris (2-chloroethyl) phosphate (TCEP) and tricresyl phosphate (TCP) were selected to evaluate toxicity of OPEs to the soil organism like earthworm (Eisenia fetida). Histopathological examination (H&E), oxidative stress, DNA damage and RT-qPCR was used to identify the effects and potential mechanism of their toxicity. Hameatoxylin and eosin (H&E) demonstrated that intestinal cells suffered serious damage, and the observed up-regulation of chitinase and cathepsin L in mRNA levels confirmed it. Both TCEP and TCP significantly increased the DNA damage when the concentrations exceeded 1 mg/kg (p < 0.01), and a dose-response relationship was observed. In addition, TCEP and TCP also changed the acetylcholinesterase (AChE) activity and expression of genes associated with neurotoxic effects in earthworms even under exposure to low OPEs concentration (0.1 mg/kg). Moreover, genes associated with nicotinic acetylcholine receptors (nAChR) and carrier protein further demonstrated that highest concentration of TCEP (10 mg/kg) may have an overloading impact on the cholinergic system of E. fetida. Integrated Biological Response index (IBRv2) showed that TCEP exerted stronger toxicity than TCP under the same concentrations. We deduced that the observed intestinal damage, oxidative stress and neurotoxic effect might be the primary mechanisms of TCEP and TCP toxicity. This study provides insight into the toxicological effects of OPEs on earthworm model, and may be useful for risk assessment of OPEs on soil ecosystems.

Low-concentration BPF induced cell biological responses by the ERα and GPER1-mediated signaling pathways in MCF-7 breast cancer cells.

Bisphenol F (BPF), one of the alternatives to bisphenol A (BPA), can induce proliferation through the nuclear estrogen receptor ERα (estrogen receptor alpha) pathway in human breast cancer MCF-7 cells. However, the roles of membrane estrogen receptor GPER1 (G-protein-coupled receptor 1)-mediated signaling pathways in MCF-7 cell proliferation caused by BPF are unclear. The influence of BPF on MCF-7 cells was evaluated in terms of cell proliferation, intracellular calcium (Ca2+) fluctuations, and reactive oxygen species (ROS) generation. The molecular mechanisms of the cellular responses to low doses of BPF were studied through detecting the activations of ERα and GPER1-regulated PI3K/PKB or AKT (phosphatidylinotidol 3-kinase/protein kinase B) and ERK1/2 (extracellular-signa1-regulated kinase 1/2) signals. At 0.01-1 µM, BPF significantly promoted cell proliferation and elevated the levels of intracellular ROS and Ca2+. At these concentrations, BPF also significantly upregulated protein expressions of ERα, GPER1, c-myc, and cyclin D and phosphorylations of PKB and ERK1/2. Specific signal inhibitors decreased PKB and ERK1/2 phosphorylations and attenuated the effects of BPF. Silencing of GPER1 also significantly decreased BPF-induced cell proliferation. These results indicate that activating the GPER1-PI3K/PKB and ERK1/2 signals by low doses of BPF can regulate the response of MCF-7 cells and that ERα also influences the effects of exposure to BPF on the cells. The present study suggests a new mechanism by which BPF exerts relevant estrogenic action in cancer cells and also highlights the potential risks in using BPF as an alternative to BPA.

[Screening for Biological Marker of Dose-optimization in Cancer Radiotherapy].

PURPOSE AND METHODS: External radiotherapy of target regions using high-energy beams leads to excessive exposure along with individual variation in therapeutic and adverse effects. However, high-precision radiotherapy utilizes 3D-multi detector computed tomography to confirm both target position and administer radiation dose. To install the individual bioinformation in the radiotherapy plan (particularly, radiosensitivity into the target region and/or the around normal tissue), the investigation of biomarkers, which are able to estimate their radiosensitivity was performed. The aim of this investigation is to screen for suitable radiosensitivity biomarkers using the human colorectal cancer-derived HCT 116 cell line. RESULTS: We found that cell damage and micronucleus frequency significantly increased dose dependently after exposure to 6 Gy X-irradiation (1 Gy/min). In contrast, total RNA concentration (69.8-85.2 ng/ml) remained stable in the cell culture supernatant despite radiation dose variation. Additionally, 52 specific micro RNAs were detected after exposure to 6 Gy X-irradiation. CONCLUSION: These results suggest that radiosensitivity, including extent of cellular damage in target or normal tissue, can be indirectly estimated by monitoring the expression of micro RNAs.

In vitro biological outcome of laser application for modification or processing of titanium dental implants.

There are numerous functions for laser in modern implant dentistry including surface treatment, surface coating, and implant manufacturing. As laser application may potentially improve osseointegration of dental implants, we systematically reviewed the literature for in vitro biological responses to laser-modified or processed titanium dental implants. The literature was searched in PubMed, ISI Web, and Scopus, using keywords "titanium dental implants," "laser," "biocompatibility," and their synonyms. After screening the 136 references obtained, 28 articles met the inclusion criteria. We found that Nd:YAG laser was the most commonly used lasers in the treatment or processing of titanium dental implants. Most of the experiments used cell attachment and cell proliferation to investigate bioresponses of the implants. The most commonly used cells in these assays were osteoblast-like cells. Only one study was conducted in stem cells. These in vitro studies reported higher biocompatibility in laser-modified titanium implants. It seems that laser radiation plays a vital role in cell response to dental implants; however, it is necessary to accomplish more studies using different laser types and parameters on various cells to offer a more conclusive result.