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Copyright of Mund-, Kiefer- und Gesichtschirurgie is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Oral & Maxillofacial Surgery is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Emerging contaminants (ECs) of significant concern are widely distributed throughout the environment due to various industrial practices and human activities. Given the alarming ecological threats and potential risks that ECs pose to human health and aquatic life, even at trace concentrations, it is imperative to develop innovative technologies to effectively address these challenges. The biophotoelectrochemistry (BPEC) system, which integrates microbial cells with photosensitizers for solar-to-chemical conversion, holds great potential as an efficient strategy for the removal of ECs. In this review, we provide new insights into the BPEC system for the ECs treatment by systematically summarizing the classification, sources, and environmental occurrence of ECs. Additionally, we explore the research progress and degradation mechanisms in ECs removal with BPEC. Finally, the current challenges and future perspectives for the applications of the BPEC system in the ECs treatment are analyzed. This review aims to promote the development of BPEC technology for ECs treatment, offering a promising prospect for environmental remediation, circular economy, and clean-energy production. [ABSTRACT FROM AUTHOR]

Copyright of Mund-, Kiefer- und Gesichtschirurgie is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Oral & Maxillofacial Surgery is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: Titanium mesh provides three-dimensional stability, it is easier and quick in placement, highly malleable and adaptable hence, proved to be worth in restoring the function and form in cases of comminuted maxillofacial fractures. Materials and Methods: A total of 12 patients were included in this retrospective study at Department of Oral and maxillofacial surgery, Sri Rajiv Gandhi College of Dental Science and Hospital, from December 2015 to June 2020. Out of 12 patients, 7 reported with frontal bone fracture and 5 reported with mandibular fracture. Patients were followed up for upto 18 months to evaluate efficacy of titanium mesh on postoperative long-term healing, aesthetic outcomes and return to normal function were evaluated. Results: The results have shown that titanium mesh has low complication rates and the ability to maintain occlusion and chewing postoperatively. Union occurred without complication in 90% of fractures, and patients treated for frontal bone fracture had excellent cosmetic results. Conclusion: The semi rigid nature of the titanium mesh fixation allows micro movement at the healing bone ends, reduces stress shielding effect which may improve functional bone healing. Bony continuity of the mandible can be restored providing three-dimensional morphology and stability. The versatile placement of screws is the principal advantage. [ABSTRACT FROM AUTHOR]

Copyright of Die MKG-Chirurgie is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Mastocytosis is a neoplasm characterized by a clonal proliferation of mast cells, which accumulate in one or multiple organs, associated with an extremely heterogeneous clinical presentation. The disease can be limited to the skin (cutaneous mastocytosis) that is mostly seen in childhood and usually behaves in a benign fashion. Adult patients most often present with systemic disease with or without skin lesions. This includes indolent forms such as indolent systemic mastocytosis and its subvariant bone marrow mastocytosis, and smoldering systemic mastocytosis as well as aggressive forms including aggressive systemic mastocytosis, systemic mastocytosis with an associated myeloid neoplasm (previously called systemic mastocytosis with an associated hematologic neoplasm), and mast cell leukemia. In addition, mast cell sarcoma is a rare aggressive form of mastocytosis that can present in the skin as well as at extracutaneous sites. This review article focuses on the updates in mastocytosis of the 2022 international consensus classification (ICC). [ABSTRACT FROM AUTHOR]

Evidence from both laboratory and field studies has shown that currently used synthetic and naturally occurring chemical substances may potentially disrupt invertebrate endocrine systems, although the extent of this in field populations remains unclear. Translating concerns about potential endocrine disrupting chemicals (EDCs) into practical and effective regulatory action is currently hampered by the breadth of invertebrate endocrinology when compared to the better understood vertebrate systems, a lack of fundamental knowledge about the endocrinology of many invertebrate groups, and the resulting uncertainty when making regulatory decisions. This commentary (i) outlines the breadth of invertebrate endocrine pathways for which European Union regulation of potential EDCs may be relevant; (ii) reviews the extent to which current knowledge meets regulatory requirements for invertebrates, including an assessment of the suitability of current invertebrate test guidelines for detecting endocrine modes of action; and (iii) proposes a roadmap towards the regulation of potential EDCs with greater confidence, based on the Adverse Outcome Pathway (AOP) concept and a focus on identifying Molecular Initiating Events (MIEs) within AOPs. We conclude there are no validated tools to determine any invertebrate endocrine mode of action in vitro or in vivo. However, there are commonly used invertebrate toxicity tests which might capture adverse effects that could potentially result from an endocrine mode of action but would not identify the causal mechanisms. Therefore, EU regulatory requirements for the identification of EDCs cannot currently be satisfied for invertebrates, either in general or for the specific invertebrates used in standard ecotoxicological studies. We propose that the most important research need is compilation of a comprehensive list of endocrine-related MIEs across invertebrate taxa via use of high-throughput 'omics in combination with bioinformatics reverse engineered analyses. Although tractable, such an approach would require significant resource investment for development and implementation. [ABSTRACT FROM AUTHOR]

Objectives: Dental implants are cylindrical metallic screws inserted into the jawbone to replace missing teeth. Their location may affect the pattern of fractures that occur as a result of the traumatic forces to the mandible. The aim of this study was to investigate possible influences of dental implants on the patterns of mandibular fractures triggered by external forces. Material and methods: In this observational cross-sectional study, a total of 390 patients with mandibular fractures diagnosed between February 2016 and December 2020 were examined and the presence or absence of dental implants in the fracture gap was noted. Clinical and radiological data were analyzed in relation to the fracture line, the dental status, and the location of any implants. Results: A total of 16 patients (4.1%) had previously placed dental implants in the mandible. Various fracture patterns were observed. Some yielded typical fracture lines located in the anatomically weak areas along the roots of the incisors, the mental foramina, and long-rooted molars. Occasionally, fracture lines were detected in combination with condylar fractures. Dental implants were not directly involved in any fracture line, except one. In that case, the fracture line extended from the alveolar process straight along the implant body, mimicking initial disintegration of the implant, with erosion of the surrounding bone. Conclusions: Once dental implants have osseointegrated, mandibular fractures are rarely projected along the implant surface. Clinical relevance: This observational retrospective cross-sectional study failed to associate mandibular fracture lines with the presence of dental implants. [ABSTRACT FROM AUTHOR]

Indigenous populations are disproportionately affected by type 2 diabetes (T2DM) compared to non-Indigenous people. Of importance, the prevalence of T2DM is greater amongst females than males in First Nations communities, in contrast to higher male prevalence reported in non-Indigenous Canadians. Therefore, in this study we extend our previously published work with respect to females, and the potential association between environmental exposures to organochlorine pesticides, such as dichlorodiphenyltrichloroethane (DDT), and dichlorodiphenyldichloroethylene (DDE) to explain the greater prevalence of T2DM among Indigenous females compared to males. Using data from the Multi-Community Environment-and-Health Study, Principal Component Analysis (PCA), examined 9-polychlorinated biphenyl congeners, 7-organic pesticides, and 4-metal/metalloids. Modified Poisson regression with robust error variance estimated adjusted prevalence ratios (PR) and corresponding 95% confidence intervals (95% CI), regressing prevalent T2DM on the newly derived principal components (PC), adjusting for a priori covariates, including parity. We further examined the relationship between high detection concentrations of DDT and tertials of categorized DDE exposures on T2DM among Indigenous Cree women. Among 419 female participants, 23% (n = 95) had physician-diagnosed T2DM. PCA analysis show that DDT and Lead (Pb) loaded highly on the second axis (PC-2), although in opposite directions, indicating the different exposure sources. As previously published, T2DM was significantly associated with PC-2 across adjusted models, however, after further adjusting for parity in this analysis, T2DM was no longer significantly associated with increasing PC-2 scores (PR = 0.88, 95% 0.76, 1.03). Furthermore, we found that the highest detectable levels of DDT, and tertiles of DDE were significantly associated with prevalent T2DM in the fully adjusted model (PR = 1.93, 1.17, 3.19), and (PR = 3.58, 1.10, 11.70), respectively. This cross-sectional analysis suggests organochlorines, specifically, detectable high exposure concentrations of DDT and DDE are associated with prevalent type 2 diabetes, signifying a possible important link between parity and environmental organochlorines pesticides among Indigenous Cree women. [ABSTRACT FROM AUTHOR]

To explore the potential function of miR-9-5p in wear-particle-induced osteoclastogenesis, we examined the expression of SIRT1 and miR-9-5p in particle-induced osteolysis (PIO) mice calvariae and polyethylene (PE)-induced RAW 264.7 cells and found that SIRT1 expression was downregulated while miR-9-5p expression was upregulated in both models. We then verified that miR-9-5p targets SIRT1. miR-9-5p was found to promote PE-induced osteoclast formation from RAW 264.7 cells by tartrate-resistant acid phosphatase staining and detection of osteoclast markers, and miR-9-5p activation of the SIRT1/NF-kB signaling pathway was found in cells by detecting the expression of SIRT1/NF-kB pathway-related proteins and rescue assays. In conclusion, we found that miR-9-5p activated the SIRT1/NF-κB pathway to promote wear-particle-induced osteoclastogenesis. miR-9-5p may be a useful therapeutic target for PIO remission and treatment. [ABSTRACT FROM AUTHOR]

Retinoic acid (RA) binding proteins, CRABP1 and CRABP2, are molecular chaperones that mediate intracellular activity of RA, the key promoter of cell differentiation with tumor suppressor activity. One of the main functions of CRABP2 is delivery and transfer of RA to the nuclear receptors RAR/RXR, which leads to activation of the transcription of a wide range of retinoid-responsive genes. The functions of CRABP1 are less studied but are apparently associated with sequestration of RA in cytoplasm and limitation of its transcriptional activity, suggesting involvement of this protein in the development of RA resistance. The mechanisms regulating activity of CRABP1 are also poorly understood. Comparison of the CRABP1 level in tumor cell lines of various origins, performed for the first time here, showed absence of the CRABP1 protein in the cell lines of tumors considered to be RA-resistant, and pronounced production of this protein in the RA-sensitive cells. However, analysis carried out with a panel of breast cancer cell lines with different levels of RA-sensitivity showed that there was no correlation between the production of CRABP1 protein and the sensitivity of the cells to RA. At the same time, we found strong correlation between the expression of CRABP1 and CRABP2 proteins in all studied cell types, regardless of their origin and RA-sensitivity/resistance. Moreover, suppression of the CRABP1 level in both RA-sensitive and RA-resistant cells was shown in the cells with cells with knockdown of CRABP2 gene. The revealed CRABP2-dependent regulation of CRABP1 production is a new mechanism of the intracellular retinoic signaling system. [ABSTRACT FROM AUTHOR]

We report the synthesis and antimicrobial properties of a partially reduced dihydronathphthoquinone analogue of 2-methoxy, 5-acetoxy calamenene, extracted from Subergorgia reticulata. The growth of a pathogenic Vibrio harveyi strain was effectively controlled by the calamenene derivative 1 (Cala1) and its synthetic analog 2 (Cala2). Complete mortality of V. harveyi was observed with 2.5 and 0.5 µg mL−1 concentrations of Cala1 and Cala2, respectively. The metabolic assays demonstrated that Cala1 is a bacteriostatic agent while Cala2 showed bactericidal properties. It was confirmed that translocation of Cala2 into the cytoplasm does not induce any change to the integrity of the bacterial cell wall. The Cala2 induced damage to the genetic material of 70% of cells while genetic material of 91% of cells treated with Cala1 remained intact. The Cala2 is, therefore, proposed as a potential bactericidal compound against the aquaculture pathogen V. harveyi. The fact that the Cala2 exhibited minimal cytotoxicity to Artemia nauplii indicates its potential use as an antimicrobial agent for aquaculture operations. [ABSTRACT FROM AUTHOR]

Introduction: Trauma is steadily increasing in the modern world and thus becoming a major public problem. Maxillofacial injuries constitute a substantial proportion of cases of trauma and occur in a variety of situations like road traffic accidents, interpersonal violence, falls or as a result of contact sports. The aim of this prospective study was to evaluate the efficacy of titanium mesh for osteosynthesis of maxillofacial fractures.Materials and Methods: Fifteen patients of maxillofacial fractures who were treated with titanium mesh were included in this prospective study. The patients were evaluated preoperatively, intraoperatively and postoperatively at 7th day, 3rd week, 6th week and 12th week.Results: The mean age of fifteen patients was 31.3 years with a male:female ratio of 14:1. The most common mode of injury was road traffic accident (86.6%). The mean time interval between injury and surgical procedure was found to be 7.6 days. The majority of fracture sites (88%) were comminuted. 93.3% of the patients achieved good occlusion by 12th week postoperatively. Postoperative complications included residual hypoaesthesia in four patients and wound dehiscence in one patient.Conclusion: We conclude that titanium mesh is a versatile option for maxillofacial fractures. It provided good stabilization especially in comminuted fractures. As a fixation method, it was quick in placement and highly adaptable, and thus, it proved to be valuable in restoring the form and function in maxillofacial trauma patients. [ABSTRACT FROM AUTHOR]

Bisphenol A (BPA) is a well-known endocrine disruptor with several effects on reproduction, development, and cancer incidence, and it is highly used in the plastic industry. Bisphenol S (BPS) was proposed as an alternative to BPA since it has a similar structure and can be used to manufacture the same products. Some reports show that BPA interferes with thyroid function, but little is known about the involvement of BPS in thyroid function or how these molecules could possibly modulate at the same time the principal genes involved in thyroid physiology. Thus, the aims of this work were to evaluate in silico the possible interactions of BPA and BPS with the thyroid transcription factors Pax 8 and TTF1 and to study the actions in vivo of these compounds in zebrafish thyroid gene expression. Adult zebrafish treated with BPA or BPS showed that sodium iodide symporter, thyroglobulin, and thyroperoxidase genes were negatively or positively regulated, depending on the dose of the exposure. Human Pax 8 alignment with zebrafish Pax 8 and Rattus norvegicus TTF1 alignment with zebrafish TTF1 displayed highly conserved regions in the DNA binding sites. Molecular docking revealed the in silico interactions between the protein targets Pax 8 and TTF1 with BPA and BPS. Importance of some amino acids residues is highlighted and ratified by literature. There were no differences between the mean energy values for BPA docking in Pax 8 or TTF1. However, BPS energy values were lower in TTF1 docking compared to Pax 8 values. The number of amino acids on the protein interface was important for Pax 8 but not for TTF1. The main BPA interactions with proteins occurred through Van der Waals forces and pi-alkyl and alkyl interactions, while BPS interactions mainly occurred through carbon hydrogen bonds and conventional hydrogen bonds in addition to Van der Waals forces and pi-alkyl interactions. These data point to a possible interaction of BPA and BPS with Pax 8 and TTF1. [ABSTRACT FROM AUTHOR]

We have developed a virtual screening procedure to identify potential ligands to the aryl hydrocarbon receptor (AhR) among a set of industrial chemicals. AhR is a key target for dioxin-like compounds, which is related to these compounds' potential to induce cancer and a wide range of endocrine and immune system-related effects. The virtual screening procedure included an initial filtration aiming at identifying chemicals with structural similarities to 66 known AhR binders, followed by 3 enrichment methods run in parallel. These include two ligand-based methods (structural fingerprints and nearest neighbor analysis) and one structure-based method using an AhR homology model. A set of 6445 commonly used industrial chemicals was processed, and each step identified unique potential ligands. Seven compounds were identified by all three enrichment methods, and these compounds included known activators and suppressors of AhR. Only approximately 0.7% (41 compounds) of the studied industrial compounds was identified as potential AhR ligands and among these, 28 compounds have to our knowledge not been tested for AhR-mediated effects or have been screened with low purity. We suggest assessment of AhR-related activities of these compounds and in particular 2-chlorotrityl chloride, 3- p-hydroxyanilino-carbazole, and 3-(2-chloro-4-nitrophenyl)-5-(1,1-dimethylethyl)-1,3,4-oxadiazol-2(3H)-one. [ABSTRACT FROM AUTHOR]

Evidence regarding carcinogenic mechanisms serves a critical role in International Agency for Research on Cancer (IARC) Monograph evaluations. Three recent IARC Working Groups pioneered inclusion of the US Environmental Protection Agency (EPA) ToxCast program high-throughput screening (HTS) data to supplement other mechanistic evidence. In Monograph V110, HTS profiles were compared between perfluorooctanoic acid (PFOA) and prototypical activators across multiple nuclear receptors. For Monograph V112-113, HTS assays were mapped to 10 key characteristics of carcinogens identified by an IARC expert group, and systematically considered as an additional mechanistic data stream. Both individual assay results and ToxPi-based rankings informed mechanistic evaluations. Activation of multiple nuclear receptors in HTS assays showed that PFOA targets not only peroxisome proliferator activated receptors, but also other receptors. ToxCast assays substantially covered 5 of 10 key characteristics, corroborating literature evidence of "induces oxidative stress" and "alters cell proliferation, cell death or nutrient supply" and filling gaps for "modulates receptor-mediated effects." Thus, ToxCast HTS data were useful both in evaluating specific mechanistic hypotheses and in contributing to the overall evaluation of mechanistic evidence. However, additional HTS assays are needed to provide more comprehensive coverage of the 10 key characteristics of carcinogens that form the basis of current IARC mechanistic evaluations. [ABSTRACT FROM AUTHOR]

Trophocytes and oenocytes of honeybees are used in studies of cellular senescence, but their cellular energy metabolism with age is poorly understood. In this study, the molecules involved in cellular energy metabolism were evaluated in the trophocytes and oenocytes of young and old worker bees. The results revealed that (i) β-oxidation and protein synthesis decreased with age, (ii) fat and glycogen accumulation increased with age, and (iii) glycolysis did not change with age. These results indicate that the trophocytes and oenocytes of young bees have higher activity of cellular energy metabolism compared with old worker bees and that aging results in a decline in the cellular energy metabolism of worker bees. [ABSTRACT FROM AUTHOR]

SIRT1 is the most evolutionarily conserved mammalian sirtuin, and it plays a vital role in the regulation of metabolism, stress responses, genome stability, and ageing. As a stress sensor, SIRT1 deacetylase activity is significantly increased during stresses, but the molecular mechanisms are not yet fully clear. Here, we show that SIRT1 is dynamically modified with O-GlcNAc at Ser 549 in its carboxy-terminal region, which directly increases its deacetylase activity both in vitro and in vivo. The O-GlcNAcylation of SIRT1 is elevated during genotoxic, oxidative, and metabolic stress stimuli in cellular and mouse models, thereby increasing SIRT1 deacetylase activity and protecting cells from stress-induced apoptosis. Our findings demonstrate a new mechanism for the activation of SIRT1 under stress conditions and suggest a novel potential therapeutic target for preventing age-related diseases and extending healthspan. [ABSTRACT FROM AUTHOR]

Diabetes and obesity are characterized by insulin resistance and chronic low-grade inflammation. An elevated plasma concentration of lipopolysaccharide (LPS) caused by increased intestinal permeability during diet-induced obesity promotes insulin resistance in mice. Here, we show that LPS induces endoplasmic reticulum (ER) stress and protein levels of P300, an acetyltransferase involved in glucose production. In high-fat diet fed and genetically obese ob/ob mice, P300 translocates from the nucleus into the cytoplasm of hepatocytes. We also demonstrate that LPS activates the transcription factor XBP1 via the ER stress sensor IRE1, resulting in the induction of P300 which, in turn, acetylates IRS1/2, inhibits its association with the insulin receptor, and disrupts insulin signaling. Pharmacological inhibition of P300 acetyltransferase activity by a specific inhibitor improves insulin sensitivity and decreases hyperglycemia in obese mice. We suggest that P300 acetyltransferase activity may be a promising therapeutic target for the treatment of obese patients. [ABSTRACT FROM AUTHOR]

Nanomedicine offers remarkable options for new therapeutic avenues. As methods in nanomedicine advance, ethical questions conjunctly arise. Nanomedicine is an exceptional niche in several aspects as it reflects risks and uncertainties not encountered in other areas of medical research or practice. Nanomedicine partially overlaps, partially interlocks and partially exceeds other medical disciplines. Some interpreters agree that advances in nanotechnology may pose varied ethical challenges, whilst others argue that these challenges are not new and that nanotechnology basically echoes recurrent bioethical dilemmas. The purpose of this article is to discuss some of the ethical issues related to nanomedicine and to reflect on the question whether nanomedicine generates ethical challenges of new and unique nature. Such a determination should have implications on regulatory processes and professional conducts and protocols in the future. [ABSTRACT FROM AUTHOR]

Endocrine-disrupting chemicals (EDCs) have the ability to inhibit normal hormonal levels and may exert an array of inimical consequences in human health. These toxins have special adverse effects in women. This review summarizes recent literature reporting on endocrine-disrupting chemicals, specifically the effects induced by parabens from personal care products and cosmetics, and bisphenol A (BPA) found in food containers, with association to adverse effects on women's health. Finally, the review provides recommendation on utilizing such EDCs to better meet the needs of consumers, while avoiding these chemical modifiers. [ABSTRACT FROM AUTHOR]

The scarcity of clean water affecting many parts of the world encourages efforts to improve water reclamation processes, which rely on their capability to remove diverse types of water pollutants and contaminants. Thus, this study reports the application of bamboo fiber powders as potential low-cost sorbent for removal of noxious organic compounds in aqueous solution. Bisphenol A, a biorefractory endocrine disruptor compound, was chosen as model compound in order to easily follow the separation process. Principal component analysis of the FTIR spectra and BET surface area measurements were performed on treated bamboo fiber powders. Treatment of the raw powders with alkali, ionic and non-ionic surfactants appeared to improve the bisphenol A removal performance of the bamboo fiber powders with the best removal efficiency reached at 39 % for a sorbent dosage of 4 g L gained after a bamboo treatment using the cationic surfactant. Effects of contact time, sorbent dosage, and particle sizes (55, 300, and 1000 μm) of cationic surfactant-treated bamboo fiber powders towards removal of bisphenol A were further assessed in a batch system with an optimum removal observed for 55 μm in particle size. [ABSTRACT FROM AUTHOR]

The review considers the effect of progestins on the function, proliferation, and apoptosis of cells of various organs in health and noncancerous disorders. Data are summarized to describe the mechanism of progestin action through various progesterone receptors and sensors and the regulation of their levels. The effects of progestins depend on the cell phenotype, including the composition and proportion of different receptors, activity of signaling pathways, and expression of transcription factor coregulators and steroid metabolism enzymes. The role paracrine regulation plays in the progestin effect is described. Particular attention is paid to the progestin effect on the tissues where progestins are thought or known to affect carcinogenesis or to stimulate or suppress the tumor growth, that is, to modulate cell proliferation, apoptosis, and the epithelial-mesenchymal transition. [ABSTRACT FROM AUTHOR]

Photodynamic impact on animal cerebral cortex using water-soluble Bengal Rose as a photosensitizer, which does not cross the blood-brain barrier and remains in blood vessels, induces platelet aggregation, vessel occlusion, and brain tissue infarction. This reproduces ischemic stroke. Irreversible cell damage within the infarction core propagates to adjacent tissue and forms a transition zone - the penumbra. Tissue necrosis in the infarction core is too fast (minutes) to be prevented, but much slower penumbral injury (hours) can be limited. We studied the changes in morphology and protein expression profile in penumbra 1 h after local photothrombotic infarction induced by laser irradiation of the cerebral cortex after Bengal Rose administration. Morphological study using standard hematoxylin/eosin staining showed a 3-mm infarct core surrounded by 1.5-2.0 mm penumbra. Morphological changes in the penumbra were lesser and decreased towards its periphery. Antibody microarrays against 224 neuronal and signaling proteins were used for proteomic study. The observed upregulation of penumbra proteins involved in maintaining neurite integrity and guidance (NAV3, MAP1, CRMP2, PMP22); intercellular interactions (N-cadherin); synaptic transmission (glutamate decarboxylase, tryptophan hydroxylase, Munc-18-1, Munc-18-3, and synphilin-1); mitochondria quality control and mitophagy (PINK1 and Parkin); ubiquitin-mediated proteolysis and tissue clearance (UCHL1, PINK1, Parkin, synphilin-1); and signaling proteins (PKBα and ERK5) could be associated with tissue recovery. Downregulation of PKC, PKCβ1/2, and TDP-43 could also reduce tissue injury. These changes in expression of some neuronal proteins were directed mainly to protection and tissue recovery in the penumbra. Some upregulated proteins might serve as markers of protection processes in a penumbra. [ABSTRACT FROM AUTHOR]

Microglial activation has been reported to play an important role in neurodegenerative diseases by producing pro-inflammatory cytokines. Bisphenol A (BPA, 2,2-bis (4-hydroxyphenyl) propane), known as a ubiquitous endocrine-disrupting chemical, is reported to perform both mimic- and anti-estrogen properties; however, whether it affects cytokine production or immune response in central nervous system remains unclear. The present study was aimed to explore whether BPA was involved in inflammatory action and to investigate the potential mechanisms in microglial cells. BV2, the murine microglial cell line, was used in the present work as the cell model. BPA-associated morphologic changes, cytokine responses, and signaling events were examined using immunofluorescence analysis, real-time PCR, enzyme-linked immunosorbent assay, and western blot. Our results indicated that BPA increased BV2 cells activation and simultaneously elevated tumor necrosis factor-α and interleukin 6 expression, which could be partially reversed by estrogen receptor antagonist, ICI182780. In addition, the c-Jun N-terminal protein kinase (JNK) inhibitor (SP600125), rather than ERK1/2 blocker (PD98059), displayed anti-inflammatory properties on BPA-elicited cytokine responses. Moreover, the inflammatory transcription factor NF-κB was specifically activated by BPA as well. These results, taken together, suggested that BPA may have functional effects on the response of microglial cell activation via, in part, the estrogen receptor, JNK, ERK mitogen-activated protein kinase, and NF-κB signaling pathways with its subsequent influence on pro-inflammatory action. [ABSTRACT FROM AUTHOR]

Estrogenic endocrine-disrupting chemicals (EDCs) are exogenous substances that act as competitive inhibitors of estrogen in the endocrine system. By disrupting the endocrine system, EDCs can cause severe disabilities and diseases, including cancers and altered sexual development. Although the influence of these molecules in the endocrine system is evident, the effects of EDCs on the immune system as well as their cytotoxicity have been poorly examined. Therefore, we selected 21 EDCs that are commonly found in Korean ecosystems, such as surface waters and effluents, and studied their immunologic effects by comparing nitric oxide (NO) production and cytotoxicity in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells (RAW cells), a macrophage cell line. Among the EDCs tested, fenitrothion (FTH) inhibited the messenger RNA (mRNA) expression of inducible NO synthase (iNOS), resulting in reduced NO production, while treatment with andostenedione (AD), diethyl phthalate, di-n-butyl phthalate (DBP), estriol, or molinate decreased production of NO in an iNOS-independent fashion. In contrast, benzo(a)pyrene (B(a)P) increased the production of NO in RAW cells. In addition, AD, DBP, or FTH inhibited the mRNA expression of tumor necrosis factor alpha or interleukin-1 beta. Treatment with 17-α-ethynylestradiol, 17-β-estradiol, 4-n-butyl phenol, or alachlor induced apoptosis of RAW cells, while dicyclohexyl phthalate and B(a)P caused cell death in an apoptosis-independent manner. These data suggest that EDCs can influence the immune response to pathogens by modulating the functions of macrophages. [ABSTRACT FROM AUTHOR]

Chronic obstructive pulmonary disease (COPD) is characterized by airflow limitation that is associated with chronic inflammatory response to noxious particles or gases. The airflow limitation may be explained by hypersecretion of mucus, thickening and fibrosis of small airways and alveolar wall destruction in emphysema. Sirtuins, a group of class III deacetylases, have gained considerable attention for their positive effects on aging-related disease, such as cancer, cardiovascular disease, neurodegenerative diseases, osteoporosis and COPD. Among the seven mammalian sirtuins, SIRT1-SIRT7, SIRT1 and SIRT6 are considered to have protective effects against COPD. In the lungs, SIRT1 inhibits autophagy, cellular senescence, fibrosis, and inflammation by deacetylation of target proteins using NAD as co-substrate and is therefore linked to the redox state. In addition to SIRT1, SIRT6 have also been shown to improve or slow down COPD. SIRT6 is associated with redox state and inhibits cellular senescence and fibrosis. Therefore, activation of SIRT1 and SIRT6 might be an attractive approach for novel therapeutic targets for COPD. The present review describes the protective effects of SIRT1 and SIRT6 against COPD and their target proteins involved in the pathophysiology of COPD. [ABSTRACT FROM AUTHOR]

Renal fibrosis is the histological manifestation of a progressive, usually irreversible process causing chronic and end-stage kidney disease. We performed genome-wide transcriptome studies of a large cohort (n = 95) of normal and fibrotic human kidney tubule samples followed by systems and network analyses and identified inflammation and metabolism as the top dysregulated pathways in the diseased kidneys. In particular, we found that humans and mouse models with tubulointerstitial fibrosis had lower expression of key enzymes and regulators of fatty acid oxidation (FAO) and higher intracellular lipid deposition compared to controls. In vitro experiments indicated that inhibition of FAO in tubule epithelial cells caused ATP depletion, cell death, dedifferentiation and intracellular lipid deposition, phenotypes observed in fibrosis. In contrast, restoring fatty acid metabolism by genetic or pharmacological methods protected mice from tubulointerstitial fibrosis. Our results raise the possibility that correcting the metabolic defect in FAO may be useful for preventing and treating chronic kidney disease. [ABSTRACT FROM AUTHOR]

Endocrine disrupting chemicals (EDCs) alter the normal endocrine system of wildlife and humans. Among pesticides, a large number of chemicals have been identified as endocrine disruptors. Pesticides are designed to be toxic to pests and vectors of disease; however, human beings can easily be exposed to these chemicals because they are present in the environment at very low levels. In the present study, we examined the adverse effects of endocrine disrupting chemicals by screening transcripts and microRNAs. microRNAs are known as regulators of many protein coding genes. Therefore, the microRNAs regulating mRNAs were analyzed, including functional analysis. In addition, we tried to compare two types of chemicals, endocrine disruptor pesticides and EDCs. Endocrine disruptor pesticides were found to affect the reproductive or development systems by altering the Wnt signaling pathway, similar to EDCs. On the other hand, the genes involved in axon guidance and ubiquitin-mediated proteolysis were differentially regulated by treatment with endocrine disruptor pesticides compared with EDCs. [ABSTRACT FROM AUTHOR]

Androgen-disrupting chemicals (ADCs) can alter male sexual development. Although the effects of ADCs on hormone disruption have been studied, their influence on the immune response is not fully understood. To investigate the effects of ADCs on innate immunity, we tested eight candidate ADCs for their influence on macrophages by measuring nitric oxide (NO) production and cell viability. Our results showed that treatment with a mixture of lipopolysaccharide and hexachlorobenzene increased NO production in RAW 264.7 cells, a murine macrophage cell line. In contrast, compared to exposure to a negative control, exposure to di-2-ethylhexyl adipate (DEHA), benzylbutyl phthalate (BBP), testosterone (TTT), or permethrin decreased NO production. DEHA, BBP, and TTT inhibited NO production in an inducible nitric oxide synthase-dependent manner. Treatment with bisphenol A (BPA), nonylphenol (NNP), or tributyltin chloride (TBTC) reduced NO production and induced cell death. While BPA induced RAW 264.7 cell death through apoptosis, NNP and TBTC caused cell death through necrosis. These results offer insights into the influences of ADCs on the innate immune system. [ABSTRACT FROM AUTHOR]

Recently developed genomics-based tools are allowing repositioning of Food and Drug Administration (FDA)-approved drugs as cancer treatments, which were employed to identify drugs that target cancer stem cells (CSCs) of breast cancer. Gene expression datasets of CSCs from six studies were subjected to connectivity map to identify drugs that may ameliorate gene expression patterns unique to CSCs. All-trans retinoic acid (ATRA) was negatively connected with gene expression in CSCs. ATRA reduced mammosphere-forming ability of a subset of breast cancer cells, which correlated with induction of apoptosis, reduced expression of SOX2 but elevated expression of its antagonist CDX2. SOX2/CDX2 ratio had prognostic relevance in CSC-enriched breast cancers. K-ras mutant breast cancer cell line enriched for CSCs was resistant to ATRA, which was reversed by MAP kinase inhibitors. Thus, ATRA alone or in combination can be tested for efficacy using SOX2, CDX2, and K-ras mutation/MAPK activation status as biomarkers of response. [ABSTRACT FROM AUTHOR]

The purpose of this review was to provide an understanding of the role of PGC-1α in the regulation of skeletal muscle metabolism and to describe the results of studies on the association of the polymorphism gene PPARGC1A with human muscle performance. [ABSTRACT FROM AUTHOR]

Contaminants, like pesticides, polychlorinated biphenyls (PCBs), dioxins, and metals, are persistent and ubiquitous and are known to threaten the environment. Traditionally, scientists have considered the direct physiological risks that these contaminants pose. However, scientists have just begun to integrate ethology and toxicology to investigate the effects that contaminants have on behavior. This review considers the potential for contaminant effects on mating behavior. Here, we assess the growing body of research concerning disruptions in sexual differentiation, courtship, sexual receptivity, arousal, and mating. We discuss the implications of these disruptions on conservation efforts and highlight the importance of recognizing the potential for environmental stressors to affect behavioral experimentation. More specifically, we consider the negative implications for anthropogenic contaminants to affect the immediate behavior of animals and their potential to have cascading and/or long-term effects on the behavioral ecology and evolution of populations. Overall, we aim to raise awareness of the confounding influence that contaminants can have and promote caution when interpreting results where the potential for cryptic effects are possible. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of the study was to review the literature regarding the evolution of current thoughts on management of comminuted mandibular fractures (CMFs). Methods: An electronic search in PubMed was undertaken in May 2012. The titles and abstracts from these results were read to identify studies within the selection criteria. Eligibility criteria included studies published in English or German reporting clinical series of CMFs. Results: The search strategy initially identified 409 studies. Fifteen studies were identified without repetition within the selection criteria. One case report article showing significance in the development of treatment techniques was included. Additional hand-searching yielded five additional papers. Thus, a total of 21 studies were included. Conclusions: Open reduction and internal fixation (ORIF) in cases of CMFs are indicated in (a) severe injuries with significant displacement to allow restoration of pretraumatic anatomic relationships, (b) in the edentulous and semi-dentate patient, who may benefit from ORIF of CMFs when stable occlusal relationships are absent, and (c) in cases with multiple fractures of the midface, in which the mandible has to serve as a guide to reposition the midfacial bones. However, there is still a place for closed reduction/conservative treatment (CTR). ORIF in CMFs is not indicated in cases of minimally displaced comminuted fractures that could easily and adequately be treated with CTR. If the surgical team is not well versed in the nuances of rigid internal fixation, or the necessary equipment is not available, it is far better to do simple CTR. However, it would be more reasonable to refer the patient to a hospital that can provide means of ORIF in cases of clear indication of its use in CMFs. In cases where ORIF is indicated, stabilization by compression or any other form of load-sharing osteosynthesis is obviously contraindicated because small fragments cannot be compressed and are not capable of sharing loads. Thus, the ORIF of CMFs is best performed using load-bearing osteosynthesis; most experience has been gained with 2.7-mm reconstruction plates. External pin fixation could be used in cases when there is so much comminution, soft tissue disruption (mostly gunshot wounds), and there are inadequate teeth on either side of the comminuted fracture to control the spatial relationship of the remaining mandibular fragments with maxillomandibular fixation (MMF). [ABSTRACT FROM AUTHOR]

The article discusses the controversy over the effects of endocrine disrupter. It cites the study conducted by Frederick vom Saal, a neurobiologist at the University of Missouri-Columbia, on the contribution of low doses of endocrine disrupter on a wide range of human health problems. It notes other studies in which similar non-monotonic responses on a variety of endocrine disrupters, most notably BPA, an ubiquitous ingredient of polycarbonate plastics and epoxy coatings were identified.

Since the beginning of the century, the mammalian sirtuin protein family (comprising SIRT1-SIRT7) has received much attention for its regulatory role, mainly in metabolism and ageing. Sirtuins act in different cellular compartments: they deacetylate histones and several transcriptional regulators in the nucleus, but also specific proteins in other cellular compartments, such as in the cytoplasm and in mitochondria. As a consequence, sirtuins regulate fat and glucose metabolism in response to physiological changes in energy levels, thereby acting as crucial regulators of the network that controls energy homeostasis and as such determines healthspan. [ABSTRACT FROM AUTHOR]

Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors that are involved in regulating glucose and lipid homeostasis, inflammation, proliferation and differentiation. Although all of these functions might contribute to the influence of PPARs in carcinogenesis, there is a distinct need for a review of the literature and additional experimentation to determine the potential for targeting PPARs for cancer therapy and cancer chemoprevention. As PPAR agonists include drugs that are used for the treatment of metabolic diseases, a more complete understanding of the roles of PPARs in cancer will aid in determining any increased cancer risk for patients undergoing therapy with PPAR agonists. [ABSTRACT FROM AUTHOR]

Peroxisome proliferator-activated receptor-β/δ (PPARβ/δ) is a promising drug target since its agonists increase serum high-density lipoprotein; decrease low-density lipoprotein, triglycerides, and insulin associated with metabolic syndrome; improve insulin sensitivity; and decrease high fat diet-induced obesity. PPARβ/δ agonists also promote terminal differentiation and elicit anti-inflammatory activities in many cell types. However, it remains to be determined whether PPARβ/δ agonists can be developed as therapeutics because there are reports showing either pro- or anti-carcinogenic effects of PPARβ/δ in cancer models. This review examines studies reporting the role of PPARβ/δ in colon, breast, and lung cancers. The prevailing evidence would suggest that targeting PPARβ/δ is not only safe but could have anti-carcinogenic protective effects. [ABSTRACT FROM AUTHOR]

Lysine acetylation, first identified in histones, was initially thought to be a posttranslational modification occuring only in eukaryotic cells that controlled gene transcription either via remodeling chromatin or altering the transcriptional machinery. Recent studies, however, have shown that acetylation is a well-conserved metabolic regulatory mechanism that plays critical roles in regulating and coordinating cell metabolism. Acetylation regulates metabolism through controlling gene transcription, altering the metabolic enzymes activity and possibly other functional aspects, of metabolic enzymes. In this review, we provide an overview of the roles and significance of acetylation in metabolic regulation. [ABSTRACT FROM AUTHOR]

The family of protein deacetylases represented by yeast Sir2 has been the focus of intense investigation because of the longevity activity of Sir2 in yeast, worms and flies. Research in mammals has mainly focused on SIRT1, the closest homologue of Sir2. Emerging evidence from mouse models is yielding a sharper picture, in which SIRT1 is a potent protector from ageing-associated pathologies, such as diabetes, liver steatosis, cardiovascular disease, neurodegeneration and, importantly, various types of cancer. [ABSTRACT FROM AUTHOR]

Secondary lymphoid organs are important locations for the initiation of adaptive immune responses. They develop before birth, and their formation requires interaction between lymphotoxin-α₁ß₂-expressing lymphoid-tissue inducer cells and lymphotoxin-ß receptor-expressing stromal organizer cells. Here, we discuss new insights into the earliest phases of peripheral lymph node and Peyer's patch formation that occur before lymphotoxin-ß receptor signalling and suggest a role for the developing nervous system. In addition, we discuss the differing requirements for the postnatal formation of mucosa-associated lymphoid tissues and tertiary lymphoid structures that develop at sites of chronic inflammation. [ABSTRACT FROM AUTHOR]

In recent years, Boolean-network-model-based approaches to dynamical analysis of complex biological networks such as gene regulatory networks have been extensively studied. One of the fundamental problems in control theory of such networks is the problem of determining whether a given substance quantity can be arbitrarily controlled by operating the other substance quantities, which we call the controllability problem. This paper proposes a polynomial-time algorithm for solving this problem. Although the algorithm is based on a sufficient condition for controllability, it is easily computable for a wider class of large-scale biological networks compared with the existing approaches. A key to this success in our approach is to give up computing Boolean operations in a rigorous way and to exploit an adjacency matrix of a directed graph induced by a Boolean network. By applying the proposed approach to a neurotransmitter signaling pathway, it is shown that it is effective. [ABSTRACT FROM AUTHOR]

The purpose of this study is to report four cases of mandibular fractures associated with endosteal implants and to discuss prevention and treatment of these types of fractures. To evaluate whether the patient's anatomy allows insertion of implants, radiological exams that demonstrate the height and the labial–lingual width are needed. To reduce the potential fracture problem, the mandible can be restrengthened with bone grafting techniques. The treatment of a fracture in an atrophic mandible is always a challenge because of the diminished central blood supply, the depressed vitality of the bone, and the dependence on the periosteal blood supply. The basic principles in fracture treatment are reduction and immobilization of the fractured site for restoration of form and function. If implants are placed in severe atrophic mandible, iatrogenic fracture of the mandible may occur during or after implant surgery because implant placement weakens the already-compromised mandible. A few millimeters of cortical bone should remain on both the labial and the lingual sites after the hole for insertion of an implant has been drilled. A 3-D surgical planning should be recommended at least in severe atrophic mandibles in order to prevent a severe reduction of bone tissue. [ABSTRACT FROM AUTHOR]

The proper functioning of the pathways that are involved in the sensing and management of nutrients is central to metabolic homeostasis and is therefore among the most fundamental requirements for survival. Metabolic systems are integrated with pathogen-sensing and immune responses, and these pathways are evolutionarily conserved. This close functional and molecular integration of the immune and metabolic systems is emerging as a crucial homeostatic mechanism, the dysfunction of which underlies many chronic metabolic diseases, including type 2 diabetes and atherosclerosis. In this Review we provide an overview of several important networks that sense and manage nutrients and discuss how they integrate with immune and inflammatory pathways to influence the physiological and pathological metabolic states in the body. [ABSTRACT FROM AUTHOR]