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International Journal of Environmental... May 2015This study was performed to assess exposure to and the risk caused by biphenyl in the workplace. Biphenyl is widely used as a heat transfer medium and as an emulsifier...
This study was performed to assess exposure to and the risk caused by biphenyl in the workplace. Biphenyl is widely used as a heat transfer medium and as an emulsifier and polish in industry. Vapor or high levels of dust inhalation and dermal exposure to biphenyl can cause eye inflammation, irritation of respiratory organs, and permanent lesions in the liver and nervous system. In this study, the workplace environment concentrations were assessed as central tendency exposure and reasonable maximum exposure and were shown to be 0.03 and 0.12 mg/m³, respectively. In addition, the carcinogenic risk of biphenyl as determined by risk assessment was 0.14 × 10⁻⁴ (central tendency exposure) and 0.56 × 10⁻⁴ (reasonable maximum exposure), which is below the acceptable risk value of 1.0 × 10⁻⁴. Furthermore, the central tendency exposure and reasonable maximum exposure hazard quotients were 0.01 and 0.06 for oral toxicity, 0.05 and 0.23 for inhalation toxicity, and 0.08 and 0.39 for reproduction toxicity, respectively, which are all lower than the acceptable hazard quotient of 1.0. Therefore, exposure to biphenyl was found to be safe in current workplace environments. Because occupational exposure limits are based on socioeconomic assessment, they are generally higher than true values seen in toxicity experiments. Based on the results of exposure monitoring of biphenyl, the current occupational exposure limits in Korea could be reviewed.
Topics: Biphenyl Compounds; Dust; Humans; Industry; Occupational Exposure; Risk Assessment; Workplace
PubMed: 25985312
DOI: 10.3390/ijerph120505116 -
Molecules (Basel, Switzerland) Sep 2014Chronic diseases such as cancer, diabetes, neurodegenerative and cardiovascular diseases are characterized by an enhanced state of oxidative stress, which may result... (Review)
Review
Chronic diseases such as cancer, diabetes, neurodegenerative and cardiovascular diseases are characterized by an enhanced state of oxidative stress, which may result from the overproduction of reactive species and/or a decrease in antioxidant defenses. The search for new chemical entities with antioxidant profile is still thus an emerging field on ongoing interest. Due to the lack of reviews concerning the antioxidant activity of lichen-derived natural compounds, we performed a review of the antioxidant potential and mechanisms of action of natural compounds isolated from lichens. The search terms "lichens", "antioxidants" and "antioxidant response elements" were used to retrieve articles in LILACS, PubMed and Web of Science published until February 2014. From a total of 319 articles surveyed, 32 met the established inclusion and exclusion criteria. It was observed that the most common isolated compound studied was usnic acid, cited in 14 out of the 32 articles. The most often described antioxidant assays for the study of in vitro antioxidant activity were mainly DPPH, LPO and SOD. The most suggested mechanisms of action were scavenging of reactive species, enzymatic activation and inhibition of iNOS. Thus, compounds isolated from lichens are possible candidates for the management of oxidative stress, and may be useful in the treatment of chronic diseases.
Topics: Antioxidant Response Elements; Antioxidants; Benzofurans; Biphenyl Compounds; Free Radical Scavengers; Humans; Lichens; Neoplasms; Oxidation-Reduction; Oxidative Stress; Picrates
PubMed: 25221871
DOI: 10.3390/molecules190914496 -
Clinical Interventions in Aging 2012Cathepsin K is a key enzyme involved in the degradation of organic bone matrix by osteoclasts. Inhibition of bone resorption observed in human and animal models... (Review)
Review
Cathepsin K is a key enzyme involved in the degradation of organic bone matrix by osteoclasts. Inhibition of bone resorption observed in human and animal models deficient for cathepsin K has identified this enzyme as a suitable target for intervention by small molecules with the potential to be used as therapeutic agents in the treatment of osteoporosis. Odanacatib (ODN) is a nonbasic selective cathepsin K inhibitor with good pharmacokinetic parameters such as minimal in vitro metabolism, long half-life, and oral bioavailability. In preclinical studies, ovariectomized monkeys and rabbits treated with ODN showed substantial inhibition of bone resorption markers along with increases in bone mineral density (BMD). Significant differences were observed in the effects of ODN treatment compared with those of other antiresorptive agents such as bisphosphonates and denosumab. ODN displayed compartment-specific effects on trabecular versus cortical bone formation, with treatment resulting in marked increases in periosteal bone formation and cortical thickness in ovariectomized monkeys whereas trabecular bone formation was reduced. Furthermore, osteoclasts remained viable. Phase I and II studies conducted in postmenopausal women showed ODN to be safe and well tolerated. After 5 years, women who received ODN 50 mg weekly continuously from year 1 (n = 13), showed BMD increases from baseline of 11.9% at the lumbar spine, 9.8% at the femoral neck, 10.9% at the hip trochanter, and 8.5% at the total hip. Additionally, these subjects maintained a low level of the urine bone resorption marker N-terminal telopeptide/creatinine (-67.4% from baseline) through 5 years of treatment, while levels of serum bone-specific alkaline phosphatase remained only slightly reduced relative to baseline (-15.3%). In women who were switched from ODN to placebo after 2 years, bone turnover markers were transiently increased and BMD gains reversed after 12 months off medication. Adverse experiences in the ODN-treated group were not significantly different from the placebo group. In conclusion, available data suggests that cathepsin K inhibition could be a promising intervention with which to treat osteoporosis. Ongoing studies are expected to provide information on the long-term efficacy in fracture reduction and safety of prolonged treatment with ODN.
Topics: Animals; Biphenyl Compounds; Bone Density Conservation Agents; Bone Remodeling; Cathepsin K; Disease Models, Animal; Female; Humans; Macaca mulatta; Osteoporosis, Postmenopausal; Rabbits
PubMed: 22866001
DOI: 10.2147/CIA.S26729 -
Bioorganic Chemistry May 2023Obesity is a complex disease defined as an excessive amount of body fat. It is considered a risk factor for several pathologies; therefore, there is an increasing...
Obesity is a complex disease defined as an excessive amount of body fat. It is considered a risk factor for several pathologies; therefore, there is an increasing interest in its treatment. Pancreatic lipase (PL) plays a key role in fat digestion, and its inhibition is a preliminary step in the search for anti-obesity agents. For this reason, many natural compounds and their derivatives are studied as new PL inhibitors. This study reports the synthesis of a library of new compounds inspired by two natural neolignans, honokiol (1) and magnolol (2) and bearing amino or nitro groups linked to a biphenyl core. The synthesis of unsymmetrically substituted biphenyls was achieved through an optimisation of the Suzuki-Miyaura cross-coupling reaction followed by the insertion of allyl chains, thus furnishing the O- and/or N-allyl derivatives, and finally, a sigmatropic rearrangement yielding in some cases, the C-allyl analogues. Magnolol, honokiol and the twenty-one synthesised biphenyls were evaluated for their in vitro inhibitory activity toward PL. Three compounds (15b, 16 and 17b) were more effective inhibitors than the natural neolignans (magnolol IC = 158.7 µM and honokiol IC = 115.5 µM) with IC of 41-44 µM. Detailed studies through kinetics suggested better inhibitory activity of the synthetic analogues compared with the natural 1 and 2. Magnolol (K = 614.3 µM; K' of 140.9 µM) and the synthetic biphenyls 15b (K = 286.4 µM; K' = 36.6 µM) and 16 (K = 176.2 µM; K' = 6.4 µM) are mixed-type inhibitors, whereas honokiol (K = 674.8 µM) and 17b (K = 249 µM) are competitive inhibitors. Docking studies corroborated these findings, showing the best fitting for intermolecular interaction between biphenyl neolignans and PL. The above outcomes highlighted how the proposed structures could be considered interesting candidates for future studies for the development of more effective PL inhibitors.
Topics: Lignans; Biphenyl Compounds
PubMed: 36913880
DOI: 10.1016/j.bioorg.2023.106455 -
FASEB Journal : Official Publication of... Apr 2022Black and Hispanic cancer patients have a higher incidence of cancer mortality. Many factors (e.g., socioeconomic differences, insufficient access to healthcare)... (Review)
Review
Exploiting the tumor immune microenvironment and immunometabolism using mitochondria-targeted drugs: Challenges and opportunities in racial disparity and cancer outcome research.
Black and Hispanic cancer patients have a higher incidence of cancer mortality. Many factors (e.g., socioeconomic differences, insufficient access to healthcare) contribute to racial disparity. Emerging research implicates biological disparity in cancer outcomes. Studies show distinct differences in the tumor immune microenvironment (TIME) in Black cancer patients. Studies also have linked altered mitochondrial metabolism to changes in immune cell activation in TIME. Recent publications revealed a novel immunomodulatory role for triphenylphosphonium-based mitochondrial-targeted drugs (MTDs). These are synthetically modified, naturally occurring molecules (e.g., honokiol, magnolol, metformin) or FDA-approved small molecule drugs (e.g., atovaquone, hydroxyurea). Modifications involve conjugating the parent molecule via an alkyl linker chain to a triphenylphosphonium moiety. These modified molecules (e.g., Mito-honokiol, Mito-magnolol, Mito-metformin, Mito-atovaquone, Mito-hydroxyurea) accumulate in tumor cell mitochondria more effectively than in normal cells and inhibit mitochondrial respiration, induce reactive oxygen species, activate AMPK and redox transcription factors, and inhibit cancer cell proliferation. Besides these intrinsic effects of MTDs in redox signaling and proliferation in tumors, MTDs induced extrinsic effects in the TIME of mouse xenografts. MTD treatment inhibited tumor-suppressive immune cells, myeloid-derived suppressor cells, and regulatory T cells, and activated T cells and antitumor immune effects. One key biological disparity in Black cancer patients was related to altered mitochondrial oxidative metabolism; MTDs targeting vulnerabilities in tumor cells and the TIME may help us understand this biological disparity. Clinical trials should include an appropriate number of Black and Hispanic cancer patients and should validate the intratumoral, antihypoxic effects of MTDs with imaging.
Topics: Atovaquone; Biphenyl Compounds; Black People; Health Status Disparities; Hispanic or Latino; Humans; Immune Checkpoint Inhibitors; Lignans; Mitochondria; Neoplasms; Oxidative Phosphorylation; Tumor Microenvironment
PubMed: 35233843
DOI: 10.1096/fj.202101862R -
Clinical Evidence Dec 2004
Review
Topics: Angiotensin-Converting Enzyme Inhibitors; Biphenyl Compounds; Blood Glucose; Captopril; Diabetic Nephropathies; Humans; Irbesartan; Losartan; Tetrazoles
PubMed: 15865682
DOI: No ID Found -
Molecules (Basel, Switzerland) Jul 202049 samples of propolis from different regions in China were collected and analyzed for their chemical compositions, contents of total flavonoids (TFC), total phenolic...
49 samples of propolis from different regions in China were collected and analyzed for their chemical compositions, contents of total flavonoids (TFC), total phenolic acid (TPC) and antioxidant activity. High-performance liquid chromatography (HPLC) analysis identified 15 common components, including key marker compounds pinocembrin, 3--acetylpinobanksin, galangin, chrysin, benzyl -coumarate, pinobanksin and caffeic acid phenethyl ester (CAPE). Cluster analysis (CA) and correlation coefficients (CC) analysis showed that these propolis could be divided into three distinct groups. Principal component analysis (PCA) and multiple linear regression analysis (MLRA) revealed that the contents of isoferulic acid, caffeic acid, CAPE, 3,4-dimethoxycinnamic acid, chrysin and apigenin are closely related to the antioxidant properties of propolis. In addition, eight peak areas decreased after reacting with 1,1-Diphenyl-2-picrylhydrazyl (DPPH) radicals, indicating that these compounds have antioxidant activity. The results indicate that the grouping and spectrum-effect relationship of Chinese propolis are related to their chemical compositions, and several compounds may serve as a better marker for the antioxidant activity of Chinese propolis than TFC and TPC. The findings may help to develop better methods to evaluate the quality of propolis from different geographic origins.
Topics: Antioxidants; Biphenyl Compounds; China; Chromatography, High Pressure Liquid; Flavonoids; Free Radical Scavengers; Humans; Phenols; Picrates; Propolis
PubMed: 32708723
DOI: 10.3390/molecules25143243 -
International Journal of Nanomedicine 2021This study was intended to utilize lecithin-based mixed polymeric micelles (MPMs) for enhancing the solubility and bioavailability of honokiol and magnolol to resolve...
OBJECTIVE
This study was intended to utilize lecithin-based mixed polymeric micelles (MPMs) for enhancing the solubility and bioavailability of honokiol and magnolol to resolve the hindrance of their extreme hydrophobicity on the clinical applications.
METHODS
Lecithin was selected to increase the volume of the core of MPMs, thereby providing a greater solubilization capacity. A series of amphiphilic polymers (sodium deoxycholate [NaDOC], Cremophor and Pluronic series) were included with lecithin for screening and optimization.
RESULTS
After preliminary evaluation and subsequentially optimization, two MPMs formulations composed of honokiol/magnolol:lecithin:NaDOC (MPMs[NaDOC]) and honokiol/magnolol:lecithin:PP123 (MPMs[PP123]) in respective ratios of 6:2:5 and 1:1:10 were optimally obtained with the mean particle sizes of 80-150 nm, encapsulation efficacy (EEs) of >90%, and drug loading (DL) of >9.0%. These MPMs efficiently stabilized honokiol/magnolol in phosphate-buffered saline (PBS) at room temperature or 4 °C and in fetal bovine serum or PBS at 37 °C. PK study demonstrated that MPMs[NaDOC] showed much improvement in enhancing bioavailability than that by MPMs[PP123] for both honokiol and magnolol. The absolute bioavailability for honokiol and magnolol after intravenous administration of MPMs[NaDOC] exhibited 0.93- and 3.4-fold increases, respectively, compared to that of free honokiol and magnolol. For oral administration with MPMs[NaDOC], the absolute bioavailability of honokiol was 4.8%, and the absolute and relative bioavailability of magnolol were 20.1% and 2.9-fold increase, respectively.
CONCLUSION
Overall, honokiol/magnolol loaded in MPMs[NaDOC] showed an improvement of solubility with suitable physical characteristics leading to enhance honokiol and magnolol bioavailability and facilitating their wider application as therapeutic agents for treating human disorders.
Topics: Administration, Oral; Animals; Biological Availability; Biphenyl Compounds; Drug Liberation; Humans; Lecithins; Lignans; Male; Micelles; Particle Size; Polymers; Rats, Sprague-Dawley; Solubility; Rats
PubMed: 33536753
DOI: 10.2147/IJN.S290444 -
Genes May 2019We sequenced the entire genomes of ten biphenyl/PCB degrading bacterial strains (KF strains) isolated from biphenyl-contaminated soil in Kitakyushu, Japan. All the...
Biphenyl/PCB Degrading Genes of Ten Bacterial Strains Isolated from Biphenyl-Contaminated Soil in Kitakyushu, Japan: Comparative and Dynamic Features as Integrative Conjugative Elements (ICEs).
We sequenced the entire genomes of ten biphenyl/PCB degrading bacterial strains (KF strains) isolated from biphenyl-contaminated soil in Kitakyushu, Japan. All the strains were Gram-negative bacteria belonging to β- and γ-proteobacteria. Out of the ten strains, nine strains carried a biphenyl catabolic gene cluster as integrative conjugative elements (ICEs), and they were classified into four groups based on the structural features of the genes. Group I (five strains) possessed genes that were very similar to the ones in KF707 (formerly KF707), which is one of the best characterized biphenyl-utilizing strains. This group of strains carried salicylate catabolic genes that were approximately 6-kb downstream of the genes. Group II (two strains) possessed and genes similar to the ones in KF707, but these strains lacked the region between and , which is involved in the downstream catabolism of biphenyl. These clusters in groups I and II were located on an integrative conjugative element that was larger than 110 kb, and they were named ICE. Our previous study demonstrated that the ICE of seudomonas KF715 in group II existed both in an integrated form in the chromosome (referred to as ICEKF715 (integrated)) and in a extrachromosomal circular form (referred to as ICE (circular)) (previously called pKF715A, 483 kb) in the stationary culture. The ICE was transferred from KF715 into P. putida AC30 and KT2440 with high frequency, and it was maintained stably as an extrachromosomal circular form. The ICEKF715 (circular) in these transconjugants was further transferred to . F39/D and then integrated into the chromosome in one or two copies. Meanwhile, group III (one strain) possessed bph genes, but not sal genes. The nucleotide sequences of the bph genes in this group were less conserved compared to the genes of the strains belonging to groups I and II. Currently, there is no evidence to indicate that the bph genes in group III are carried by a mobile element. Group IV (two strains) carried genes as ICEs (59-61 kb) that were similar to the genes found in Tn from A5 and ICE from the sp. strain KKS102. Our study found that gene islands have integrative functions, are transferred among soil bacteria, and are diversified through modification.
Topics: Biphenyl Compounds; Environmental Pollution; Gram-Negative Bacteria; Proteobacteria; Pseudomonas putida; Soil Microbiology; Soil Pollutants
PubMed: 31137913
DOI: 10.3390/genes10050404 -
Journal of Bacteriology Dec 2005Recent microarray experiments suggested that Burkholderia xenovorans LB400, a potent polychlorinated biphenyl (PCB)-degrading bacterium, utilizes up to three apparently...
Recent microarray experiments suggested that Burkholderia xenovorans LB400, a potent polychlorinated biphenyl (PCB)-degrading bacterium, utilizes up to three apparently redundant benzoate pathways and a C(1) metabolic pathway during biphenyl and benzoate metabolism. To better characterize the roles of these pathways, we performed quantitative proteome profiling of cells grown on succinate, benzoate, or biphenyl and harvested during either mid-logarithmic growth or the transition between the logarithmic and stationary growth phases. The Bph enzymes, catabolizing biphenyl, were approximately 16-fold more abundant in biphenyl- versus succinate-grown cells. Moreover, the upper and lower bph pathways were independently regulated. Expression of each benzoate pathway depended on growth substrate and phase. Proteins specifying catabolism via benzoate dihydroxylation and catechol ortho-cleavage (ben-cat pathway) were approximately an order of magnitude more abundant in benzoate- versus biphenyl-grown cells at the same growth phase. The chromosomal copy of the benzoyl-coenzyme A (CoA) (box(C)) pathway was also expressed during growth on biphenyl: Box(C) proteins were approximately twice as abundant as Ben and Cat proteins under these conditions. By contrast, proteins of the megaplasmid copy of the benzoyl-CoA (box(M)) pathway were only detected in transition-phase benzoate-grown cells. Other proteins detected at increased levels in benzoate- and biphenyl-grown cells included general stress response proteins potentially induced by reactive oxygen species formed during aerobic aromatic catabolism. Finally, C(1) metabolic enzymes were present in biphenyl-grown cells during transition phase. This study provides insights into the physiological roles and integration of apparently redundant catabolic pathways in large-genome bacteria and establishes a basis for investigating the PCB-degrading abilities of this strain.
Topics: Aerobiosis; Bacterial Proteins; Benzoates; Biphenyl Compounds; Burkholderia; Carbon; Culture Media; Cytosol; Electrophoresis, Gel, Two-Dimensional; Substrate Specificity
PubMed: 16291673
DOI: 10.1128/JB.187.23.7996-8005.2005