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- ArticleMoussa FM, Cook BP, Sondag GR, DeSanto M, Obri MS, McDermott SE, Safadi FF.Bone. 2021 04;145:115470.BACKGROUND: mir-RNAs play a role in regulating bone homeostasis. In this study we assessed the functional role of mir-RNA 150 in bone homeostasis. We also assess the effects of miR-150 deficiency on osteoblast and osteoclast differentiation and function using in vivo and in vitro approaches.
METHODS: Wild type (WT) (C57BL/6J) and miR-150 KO mice were compared for a variety of parameters. Micro-CT imaging was conducted to quantify trabecular bone mass inferior to the distal growth plate of the femur. Von Kossa staining was performed for osteoblast culture mineralization. RT-qPCR, biochemical analysis and bone histomorphometry were utilized for quantification of relevant genes and serum protein measurements. Differentiation and function of osteoblasts and osteoclasts was performed using primarily cultures and assessed the cell autonomous response of mir-RNA-150 on cell differentiation and function.
RESULTS: Mir-150 exhibited expression in a variety of tissues and increases progressively with age. Through micro-CT imaging, we found that KO mice presented reduced bone mass at 4, 8, and 16 weeks of age compared to WT mice. Furthermore, histomorphometric analysis revealed increased trabecular separation, decreased bone thickness, and decreased osteoblast number in KO compared to WT mice. Mir-150 deficiency also correlated with higher bone resorption, accompanied with significant increases in CTX-1 serum levels, and a decrease in cell apoptotic rate ex vivo. Additionally, miR-150 KO mice showed increased osteoblast differentiation and decreased osteoclastogenesis ex vivo. Luciferase assay showed increased Osteoactivin/GPNMB expression in miR-150 KO osteoblasts compared to WT cells.
CONCLUSION: Our data suggests that miR-150 influences osteoblast and osteoclast functionality and differentiation; specifically, miR-150 serves as a negative regulator for osteoblasts and a positive regulator for osteoclasts by regulating, at least in part, Osteoactivin/GPNMB expression. - ArticleOuhmad N, El Hage W, Combalbert N.Psychiatry Res. 2023 10;328:115470.The sexual abuse of women has major repercussions on several spheres of the victims' daily lives and can lead to the development of PTSD. We were interested in the existence of a specific profile of alterations in cognitive functioning in female victims of sexual violence with PTSD. A sample of 101 women was divided into three groups (44 sexually abused women with PTSD; 25 sexually abused women without PTSD; 32 non-sexually abused non-PTSD controls). Participants completed questionnaires about psycho-traumatic symptoms, emotion regulation and executive functions. The results show that the PTSD group uses more maladaptive cognitive emotion regulation strategies. In addition, overall executive functions were poorer in the PTSD group. Moreover, sexual assault, exposed with or without PTSD, is associated with deficits in executive functions, particularly inhibition. We also found positive correlations between executive difficulties and the use of non-adaptive emotion regulation strategies. These results suggest that there may be individual differences in the alterations in cognitive functioning following sexual assault.
- ArticleConner CM, van Fossan D, Read K, Cowley DO, Alvarez O, Xu SX, Webb DR, Jarnagin K.Biochem Pharmacol. 2023 04;210:115470.Monoclonal antibodies (mAbs) are one of the fastest-growing classes of drugs and have been approved to treat several diseases, including cancers and autoimmune disorders. Preclinical pharmacokinetics studies are performed to determine the therapeutically meaningful dosages and efficacy of candidate drugs. These studies are typically performed in non-human primates; however, using primates is costly and raises ethical considerations. As a result, rodent models that better mimic human-like pharmacokinetics have been generated and remain an area of active investigation. Pharmacokinetic characteristics of a candidate drug, such as half-life, are partly controlled by antibody binding to the human neonatal receptor hFCRN. Due to the abnormally high binding of human antibodies to mouse FCRN, traditional laboratory rodents do not accurately model the pharmacokinetics of human mAbs. In response, humanized rodents expressing hFCRN have been generated. However, these models generally use large inserts randomly integrated into the mouse genome. Here, we report the production and characterization of a CRISPR/Cas9-mediated hFCRN transgenic mouse termed SYNB-hFCRN. Using CRISPR/Cas9-assisted gene targeting, we prepared a strain with a simultaneous knockout of mFcrn and insertion of a hFCRN mini-gene under the control of the endogenous mouse promoter. These mice are healthy and express hFCRN in the appropriate tissues and immune cell subtypes. Pharmacokinetic evaluation of human IgG and adalimumab (Humira®) demonstrate hFCRN-mediated protection. These newly generated SYNB-hFCRN mice provide another valuable animal model for use in preclinical pharmacokinetics studies during early drug development.
- ArticleWang J, Zhang J, Zhao Y, Sun S, Wang X, He X, Wan R, Ma Y, You L.Mar Pollut Bull. 2023 Oct;195:115470.This study analysed marine debris monitoring data for Shandong from 2014 to 2022 to obtain a better understanding of marine debris stocking off-shore Shandong in order to reduce marine debris pollution and improving the ecological environment of ocean. The results indicated that the abundance of coastal marine debris was 45,832 items/km2 (1118.5 kg/km2); the abundance of small/medium sized floating marine debris was 8976 items/km2 (1.38 kg/km2); and the abundance of large floating marine debris was 35 items/km2; the abundance of seafloor debris was 104 item/km2 (0.22 kg/km2). Compared with the nationwide abundance of marine debris, the quantity density of floating marine debris in Shandong was higher; the abundance of coastal marine debris and quality density of floating marine debris were lower. The majority of the Shandong marine debris was small/medium plastic, mostly from human activities. And we found no significant correlation between precipitation and the abundance of marine debris by statistical analysis.
- ArticleDu X, Gu S, Zhang Z, Li S, Zhou Y, Zhang Z, Zhang Q, Wang L, Ju Z, Yan C, Li T, Wang D, Yang X, Peng X, Deng Y.Environ Res. 2023 04 15;223:115470.Even in the vertical dimension, soil bacterial communities are spatially distributed in a distance-decay relationship (DDR). However, whether this pattern is universal among all soil microbial taxonomic groups, and how body size influences this distribution, remains elusive. Our study consisted of obtaining 140 soil samples from two adjacent ecosystems in the Yellow River Delta (YRD), both nontidal and tidal, and measuring the DDR between topsoil and subsoil for bacteria, archaea, fungi and protists (rhizaria). Our results showed that the entire community generally fitted the DDR patterns (P < 0.001), this was also true at the kingdom level (P < 0.001, with the exception of the fungal community), and for most individual phyla (47/75) in both ecosystems and with soil depth. Meanwhile, these results presented a general trend that the community turnover rate of nontidal soils was higher than tidal soils (P < 0.05), and that the rate of topsoil was also higher than that of subsoil (P < 0.05). Additionally, microbial spatial turnover rates displayed a negative relationship with body sizes in nontidal topsoil (R2 = 0.29, P = 0.009), suggesting that the smaller the body size of microorganisms, the stronger the spatial limitation was in this environment. However, in tidal soils, the body size effect was negligible, probably owing to the water's fluidity. Moreover, community assembly was judged to be deterministic, and heterogeneous selection played a dominant role in the different environments. Specifically, the spatial distance was much more influential, while the soil salinity in these ecosystems was the major environmental factor in selecting the distributions of microbial communities. Overall, this study revealed that microbial community compositions at different taxonomic levels followed relatively consistent distribution patterns and mechanisms in this coastal area.
- ArticleWang J, Li X, Cheng Q, Lv F, Chang C, Zhang L.Carbohydr Polym. 2020 Feb 01;229:115470.The environmentally friendly materials fabricated from renewable marine resources have aroused worldwide concerns. Here, for the first time, tunicate cellulose was dissolved in LiOH/urea aqueous solution at -12 °C after ball-milling, and its molecular weight was determined with laser light scattering. Hydrogels were fabricated from the cellulose solution by regenerating in ethanol, and β-FeOOH nanoparticles (NPs) were in-situ synthesized to obtain β-FeOOH/cellulose composite hydrogels (TCH-Fe). The tunicate cellulose hydrogels (TCH) not only disperse uniformly and immobilize firmly the β-FeOOH NPs, but also acted as structural materials for continuous flow photocatalytic system. The photocatalytic degradation of methylene blue (MB) over TCH-Fe achieved up to 99.89% in 30 min under visible-light irradiation, and maintained as high as ∼98% after treatment for 8 h, indicating a highly efficient photodegradation of MB. We provided a low-cost and facile method to construct new sustainable materials derived from marine biomass with highly efficient photocatalytic properties.
- ArticleMao Q, Cui Y, Du H, Wu J, Zhou M, Ouyang H, Feng Y, Yang S.J Ethnopharmacol. 2022 Oct 05;296:115470.ETHNOPHARMACOLOGICAL RELEVANCE: San Pian decoction (SPD), a traditional Chinese medicine preparation composed of eight herbs, has been reported to alleviate migraine. However, its active ingredients and the potential mechanism of action remains unclear. The purpose of this study was to comprehensively analyze SPD for the treatment of chronic migraine based on pharmacological direction and to identify the active ingredients and pharmacological mechanism of SPD in the treatment of migraine.
MATERIALS AND METHODS: The active components in SPD were identified by AB SCIEX quadrupole time-of-flight mass spectrometer, and the prediction targets and pharmacological networks related to migraine were constructed. The mechanism of SPD in treating migraine was studied through network pharmacology, which was further verified using pharmacological experiments.
RESULTS: A total of 489 targets of 26 compounds were identified. Based on Venn analysis, we found 117 intersection targets between SPD and migraine, that is, these targets were related to the treatment of migraine. Gene ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis revealed that the treatment of migraine using SPD was related to the PI3K/AKT and MAPK signaling pathways. The effect of SPD on migraine was verified by measuring the levels of the inflammatory factors, nitric oxide (NO), interleukin (IL-6), endothelin (ET),5-hydroxytryptamine(5-HT), indoleamine 2,3-dioxygenas (IDO), tumor necrosis factor (TNF-α) and calcitonin gene-related peptide (CGRP). Lastly, real-time polymerase chain reaction and western blotting were used to verify gene and protein expression in the PI3K/AKT and MAPK signaling pathways. Expression of the genes P38, JNK, ERK, PI3K and AKT, and the protein expression of p-P38, p-JNK, p-ERK, p-AKT and p-PI3K were significantly downregulated. Our findings indicated that SPD could prevent inflammation by regulating the inflammatory cytokines and key genes and proteins in the PI3K/AKT and MAPK signaling pathways to treat migraine.
CONCLUSION: Our findings reveal that SPD could treat nitroglycerin-induced migraine by regulating p-AKT, p-pI3k, p-p38, p-ERK, p-JNK, IL-6, and TNF-α inflammatory factors in the PI3K/AKT and MAPK signaling pathways. - ArticleFeng Y, Tang Z, Zhang W.Biomed Pharmacother. 2023 Nov;167:115470.Polycystic ovarian syndrome (PCOS) is the most common endocrine and metabolic disorder in women of childbearing age, with ovulatory dysfunction, hyperandrogenism, and polycystic ovarian morphology (PCOM) as the clinical features. Androgen excess, insulin resistance, obesity, adipose tissue dysfunction, ovulatory dysfunction, and gut microbiota dysbiosis are the main pathological features and pathogenesis of PCOS and are related to systemic chronic low-grade inflammation and chronic ovarian tissue inflammation in PCOS. With the advances in immune-endocrine interaction studies, research on the role of immune cells in the occurrence and development of PCOS is gradually increasing. As the core of innate immunity, macrophages play an indispensable role in systemic inflammatory response. Meanwhile, they are involved in maintaining the stability and function of the ovary as the most abundant immune cells in ovarian tissue. Studies in humans and mice have found that the polarization of macrophages into M1 type plays multiple roles in the pathogenesis of PCOS. This review describes the distribution characteristics of macrophage subpopulations in patients and animal models with PCOS, discusses the role of macrophage-related metabolic inflammation in PCOS, and summarizes the relationship between macrophages and PCOS-related pathological features and its possible mechanisms, to further understand the pathogenesis of PCOS and reveal the role of macrophages in it. In addition, research on immune-endocrine interactions can also provide direction for finding new therapeutic targets for PCOS.
- ArticleWu Y, Chen W, Wang C, Xing D.Biosens Bioelectron. 2023 Oct 01;237:115470.Nanomaterials with intrinsic enzyme activity, referred to as nanozymes, have attracted substantial attention in recent years. Among them, phosphatase-mimicking nanozymes have become an increasingly important focus for future research, considering that phosphatase is not only one of key enzymes for phosphorous metabolism, which is essential for many biological processes (e.g., cellular regulation and signaling), but also one of extensively used biocatalytic labels in the enzyme-linked assays as well as a powerful tool enzyme in molecular biology laboratories. Nevertheless, compared with extensive oxidoreductase-mimicking nanozymes, there are a very limited number of nanozymes with phosphatase-like activity have been explored at present. The increasing demand of complex and individualized phosphatase-involved catalytic behaviors is pushing the development of more advanced phosphatase-mimicking nanozymes. Thus, we present an overview on recently reported phosphatase-like nanozymes, providing guidelines and new insights for designing more advanced phosphatase-mimicking nanozyme with superior properties.
- ArticleBelháčová-Minaříková M, Smedes F, Rusina TP, Vrana B.Environ Pollut. 2020 Dec;267:115470.Total concentrations of hydrophobic organic contaminants (HOCs) in sediment present a poor quality assessment parameter for aquatic organism exposure and environmental risk because they do not reflect contaminant bioavailability. The bioavailability issue of HOCs in sediments can be addressed by application of multi-ratio equilibrium passive sampling (EPS). In this study, riverbed sediment samples were collected during the Joint Danube Survey at 9 locations along the Danube River in 2013. Samples were ex-situ equilibrated with silicone passive samplers. Desorption isotherms were constructed, yielding two endpoints: pore water (CW:0) and accessible (CAS:0) concentration of polychlorinated biphenyls (PCBs), organochlorine pesticides (OCPs), polycyclic aromatic hydrocarbons (PAHs) and polybrominated diphenyl ethers in sediment. CW:0 concentrations of DDT and its breakdown products exhibited elevated levels in the low Danube, with the maximum in the river delta. Other investigated HOCs did not show any clear spatial trends along the river, and only a moderate CW:0 variability. CAS:0 in sediment ranged from 10 to 90% of the total concentration in sediment. CW:0 was compared with freely dissolved concentration in the overlaying surface water, measured likewise by passive sampling. The comparison indicated potential compound release from sediment to the water phase for PAHs with less than four aromatic rings, and for remaining HOCs either equilibrium between sediment and water, or potential compound deposition in sediment. Sorption partition coefficients of HOC to organic carbon correlated well with octanol-water partition coefficients (KOW), showing stronger sorption of PAHs to sediment than that of PCBs and OCPs having equal logKOW. Comparison of CW:0 values with European environmental quality standards indicated potential exceedance for hexachlorobenzene, fluoranthene and benzo[a]pyrene at several sites. The study demonstrates the utility of passive sampling as an innovative approach for risk-oriented monitoring of HOCs in river catchments.
- ArticleZhong H, Shi Z, Jiang G, Yuan Z.Water Res. 2020 Apr 01;172:115470.Microbially influenced corrosion (MIC) is the main cause of metal corrosion in anoxic environments. Biocides are often dosed to the corrosive media to inhibit and kill the microbes which cause MIC. In this study, intermittent dosages of free nitrous acid (FNA), which was previously found to be a biocide, were applied to a simulated water injection system containing carbon steel coupons with mature biofilm, to study the effect of FNA on mitigation of metal corrosion. In each treatment, 0.49 mg-N/L FNA was dosed using 200 mg-N/L nitrite at pH 6 for 24 h. The corrosion properties were monitored by open circuit potential (OCP), electrochemical impedance spectroscopy (EIS), linear polarization resistance (LPR), 3D optical profiling, and direct weight measurement. The biofilm viability was monitored by measuring cellular ATP level. The general corrosion rate (calculated by weight-loss measurement) was decreased by up to 31%, which was supported by LPR tests and reduced ATP levels of the corrosion-inducing biofilm. The 3D optical profiling results showed that FNA decreased the average pitting corrosion rate by 59%, with 2 intermittent treatments and 82-day interval over 304 days. Intermittent dosing of FNA has strong potential to be an effective and efficient strategy for controlling MIC in oil recovery infrastructure.
- ArticleYan Z, Li A, Shim H, Wang D, Cheng S, Wang Y, Li M.J Environ Manage. 2022 Sep 01;317:115470.Due to the extremely low C/N ratio, high concentration of ammonia nitrogen and refractory organic matter of mature landfill leachate (MLL), appropriate processes should be selected to effectively remove nitrogen and reduce disposal costs. Partial nitritation (PN) and anaerobic ammonia oxidation (AMX) have been used as the main nitrogen removal processes for MLL, and the sludge granulation in PN and AMX processes could contribute to high biological activity, good sedimentation performance, and stable resistance to toxicity. In this study, the O3-PN-AMX biogranules process was selected to effectively remove nitrogen from MLL without carbon addition and pH adjustment. Without uneconomical NH4+-N oxidation and wasting the alkalinity of MLL, ozone pretreatment achieved color removal, decreased humic- and fulvic-like acid substances, and alleviated the MLL toxicity on ammonia oxidizers. In addition, the ozonation of MLL could shorten the start-up time and improve the treatment efficiency and biogranules stability of PN and AMX processes. Efficient and stable nitritation was achieved in PN reactor without strict dissolved oxygen (DO) control, which was attributed to the unique structure of granular sludge, ozone pretreatment, and alternating inhibition of free ammonia and free nitric acid on nitrite oxidizers. Through the application of ozone pretreatment and granular sludge, the nitrogen removal rate (NRR) and nitrogen removal efficiency (NRE) of the O3-PN-AMX biogranules process reached 0.39 kg/m3/day and 85%, respectively, for the undiluted MLL treatment. This study might provide a novel and effective operation strategy of combined process for the efficient, economical, and stable nitrogen removal from MLL.
- ArticleYu T, Zhong X, Li D, Zhu J, Tuchin VV, Zhu D.Adv Drug Deliv Rev. 2024 Oct 29;215:115470.Advanced optical imaging provides a powerful tool for the structural and functional analysis of tissues with high resolution and contrast, but the imaging performance decreases as light propagates deeper into the tissue. Tissue optical clearing technique demonstrates an innovative way to realize deep-tissue imaging and have emerged substantially in the last two decades. Here, we briefly reviewed the basic principles of tissue optical clearing techniques in the view of delivery strategies via either free diffusion or external forces-driven advection, and the commonly-used optical techniques for monitoring kinetics of clearing agents in tissue, as well as their ex vivo to in vivo applications in multiple biomedical research fields. With future efforts on the even distribution of both clearing agents and probes, excavation of more effective clearing agents, and automation of tissue clearing processes, tissue optical clearing should provide more insights into the fundamental questions in biological events clinical diagnostics.
- ArticleVenosa A, Gow JG, Taylor S, Golden TN, Murray A, Abramova E, Malaviya R, Laskin DL, Gow AJ.Toxicol Appl Pharmacol. 2021 04 15;417:115470.Bleomycin is a cancer therapeutic known to cause lung injury which progresses to fibrosis. Evidence suggests that macrophages contribute to this pathological response. Tumor necrosis factor (TNF)α is a macrophage-derived pro-inflammatory cytokine implicated in lung injury. Herein, we investigated the role of TNFα in macrophage responses to bleomycin. Treatment of mice with bleomycin (3 U/kg, i.t.) caused histopathological changes in the lung within 3 d which culminated in fibrosis at 21 d. This was accompanied by an early (3-7 d) influx of CD11b+ and iNOS+ macrophages into the lung, and Arg-1+ macrophages at 21 d. At this time, epithelial cell dysfunction, defined by increases in total phospholipids and SP-B was evident. Treatment of mice with anti-TNFα antibody (7.5 mg/kg, i.v.) beginning 15-30 min after bleomycin, and every 5 d thereafter reduced the number and size of fibrotic foci and restored epithelial cell function. Flow cytometric analysis of F4/80+ alveolar macrophages (AM) isolated by bronchoalveolar lavage and interstitial macrophages (IM) by tissue digestion identified resident (CD11b-CD11c+) and immature infiltrating (CD11b+CD11c-) AM, and mature (CD11b+CD11c+) and immature (CD11b+CD11c-) IM subsets in bleomycin treated mice. Greater numbers of mature (CD11c+) infiltrating (CD11b+) AM expressing the anti-inflammatory marker, mannose receptor (CD206) were observed at 21 d when compared to 7 d post bleomycin. Mature proinflammatory (Ly6C+) IM were greater at 7 d relative to 21 d. These cells transitioned into mature anti-inflammatory/pro-fibrotic (CD206+) IM between 7 and 21 d. Anti-TNFα antibody heightened the number of CD11b+ AM in the lung without altering their activation state. Conversely, it reduced the abundance of mature proinflammatory (Ly6C+) IM in the tissue at 7 d and immature pro-fibrotic IM at 21 d. Taken together, these data suggest that TNFα inhibition has beneficial effects in bleomycin induced injury, restoring epithelial function and reducing numbers of profibrotic IM and the extent of pulmonary fibrosis.
- ArticleFichna JP, Karolczak J, Potulska-Chromik A, Miszta P, Berdynski M, Sikorska A, Filipek S, Redowicz MJ, Kaminska A, Zekanowski C.PLoS One. 2014;9(12):e115470.Desmin is a muscle-specific intermediate filament protein which forms a network connecting the sarcomere, T tubules, sarcolemma, nuclear membrane, mitochondria and other organelles. Mutations in the gene coding for desmin (DES) cause skeletal myopathies often combined with cardiomyopathy, or isolated cardiomyopathies. The molecular pathomechanisms of the disease remain ambiguous. Here, we describe and comprehensively characterize two DES mutations found in Polish patients with a clinical diagnosis of desminopathy. The study group comprised 16 individuals representing three families. Two mutations were identified: a novel missense mutation (Q348P) and a small deletion of nine nucleotides (A357_E359del), previously described by us in the Polish population. A common ancestry of all the families bearing the A357_E359del mutation was confirmed. Both mutations were predicted to be pathogenic using a bioinformatics approach, including molecular dynamics simulations which helped to rationalize abnormal behavior at molecular level. To test the impact of the mutations on DES expression and the intracellular distribution of desmin muscle biopsies were investigated. Elevated desmin levels as well as its atypical localization in muscle fibers were observed. Additional staining for M-cadherin, α-actinin, and myosin heavy chains confirmed severe disruption of myofibrill organization. The abnormalities were more prominent in the Q348P muscle, where both small atrophic fibers as well large fibers with centrally localized nuclei were observed. We propose that the mutations affect desmin structure and cause its aberrant folding and subsequent aggregation, triggering disruption of myofibrils organization.
- ArticleLouvel S, Soulier A.Soc Sci Med. 2022 12;314:115470.OBJECTIVES: This article compares research on biological embedding and the embodiment of social experiences, two concepts proposed in the 1990s to introduce a new perspective on the social production of health inequalities. We draw on Ludwig Fleck's concept of 'thought style' (1935/2008) to question the possible emergence of a common research program around the processes by which the social becomes biological.
METHODS: We compiled a corpus of 322 articles referring to either biological embedding or to the embodiment of social experiences, identified in the Web of Science core collection and published from 1990 to 2021. We analyzed the articles' use of these concepts using scientometric indicators and qualitative content analysis.
RESULTS: Initial differences between the research agendas associated with biological embedding and embodiment are strengthened as both concepts circulate around scientific communities studying the social production of health inequalities. Thought styles formed around embedding and embodiment differ significantly in terms of shared references, sets of methods and research questions, and policy recommendations. Research on biological embedding forms a thought style shared by researchers in the biomedical and public health sciences. Conversely, the concept of embodiment of social experiences connects perspectives from biomedical, public health, human and social sciences, and gathers three thought styles, one identical to that of biological embedding and two formed in social epidemiology and in medical anthropology.
CONCLUSIONS: Acknowledging the differences between the concepts and divergences in their evolution provides an opportunity for identification of topics where thought styles are either complementary or in tension. - ArticleSantos DC, Henriques RR, Junior MAAL, Farias AB, Nogueira TLDC, Quimas JVF, Romeiro NC, Silva LLD, Souza ALF.Bioorg Med Chem. 2020 05 15;28(10):115470.Acylhydrazones 1a-o, derived from isoniazid, were synthesized and evaluated for Myeloperoxidase (MPO) and Acetylcholinesterase (AChE) inhibition, as well as their antioxidant and metal chelating activities, with the purpose of investigating potential multi-target profiles for the treatment of Alzheimer's disease. Synthesized compounds were tested using the 2,2-diphenyl-2-picrylhydrazyl (DPPH) method and 1i, 1j and 1 m showed radical scavenging ability. Compounds 1b, 1 h, 1i, 1 m and 1o inhibited MPO activity (10 μM) at 96.1 ± 5.5%, 90 ± 2.1%, 100.3 ± 1.7%, 80.1 ± 9.4% and 82.2 ± 10.6%, respectively, and only compound 1 m was able to inhibit 54.2 ± 1.7% of AChE activity (100 μM). Docking studies of the most potent compound 1 m were carried out, and the computational results provided the theoretical basis of enzyme inhibition. Furthermore, compound 1 m was able to form complexes with Fe2+ and Zn2+ ions in a 2:1 ligand:metal ratio according to the Job Plot method.
- ArticleRussello G, Moramarco A, Vizzini L, Farina C, Fontana L, Carretto E.Diagn Microbiol Infect Dis. 2021 Nov;101(3):115470.Rapid identification of causative microorganisms of microbial keratitis (MK) and knowledge of the most common local pathogens are prerequisites for rational antimicrobial therapy. We retrospectively reviewed the characteristics of MK diagnosed at the IRCCS Arcispedale Santa Maria Nuova of Reggio Emilia (Italy) in a 5-years period, where the Ophthalmologist Unit is a reference center for corneal infections. During the study period, 183 MK were evaluated through corneal scrapings cultures. The positivity rate was 54,1%. A total of 107 microorganisms have been isolated: Acanthamoeba species was the etiologic agent in 19 cases. Pseudomonas aeruginosa and Staphylococcus aureus were more frequently isolated in bacterial keratitis, while Fusarium spp., Candida albicans, and Alternaria alternata were predominant among the fungal isolates. Strict cooperation between ophthalmologists and clinical microbiologists is advisable to allow the best diagnostic approach for MK.
- ArticleLu Y, Guo Y, Zhang Y, Sun H, Wu X.J Pharm Biomed Anal. 2023 Sep 05;233:115470.5-Hydroxymethyl-2-furaldehyde (5-HMF) is a kind of aldehyde compound with highly active furan ring, which is generated by dehydration of glucose, fructose, and other monosaccharides. It widely exists in drugs, foods, health products, cosmetics, and traditional Chinese medicine preparations with high sugar content. Due to the toxicity, the concentration of 5-HMF was always monitored to identify non-conformities and adulteration, as well as ensure the process efficiency, traceability and safety in foods or drugs in the pharmacopoeias of various countries. Herein, a comprehensive forced degradation study was performed to characterize the degradation products (DPs) of 5-HMF under hydrolytic (neutral, acidic, and alkaline) degradation, oxidative, thermal, humidity, and photolytic degradation conditions. A total of five degradants were identified, and two of them (DP-3 and DP-5) were novel DPs first reported in our study. Major DPs (i.e., DP-1 and DP-2) with relatively high peak areas were isolated using semi-preparative HPLC and characterized by LC-LTQ/Orbitrap and NMR. 5-HMF was only stable in alkaline hydrolysis condition. In addition, the degradation pathways and mechanism of these DPs were also explained using LC-LTQ/Orbitrap. In silico toxicity and metabolism behavior of the DPs were evaluated using Derek Nexus and Meteor Nexus software, respectively. The predicted toxicity data indicated that both the drug 5-HMF and its DPs bear the potential of hepatotoxicity, mutagenicity, chromosome damage, and skin sensitisation. Our research may be beneficial for the quality control and suitable storage conditions of 5-HMF.
- ArticleWu H, Wang LS, Li P, Yu J, Cheng S, Yu G, Ahmad M, Meng XL, Luo H, Xu BX.Eur J Med Chem. 2023 Aug 05;256:115470.A series of new N-aryl-2-trifluoromethylquinazoline-4-amine analogs were designed and synthesized based on structure optimization of quinazoline by introducing a trifluoromethyl group into 2-position. The structures of the twenty-four newly synthesized compounds were confirmed by 1H NMR, 13C NMR and ESI-MS. The in vitro anti-cancer activity against chronic myeloid leukemia cells (K562), erythroleukemia cells (HEL), human prostate cancer cells (LNCaP), and cervical cancer cells (HeLa) of the target compounds was evaluated. Among them, compounds 15d, 15f, 15h, and 15i showed the significantly (P < 0.01) stronger growth inhibitory activity on K562 than those of the positive controls of paclitaxel and colchicine, while compounds 15a, 15d, 15e, and 15h displayed significantly stronger growth inhibitory activity on HEL than those of the positive controls. However, all the target compounds exhibited weaker growth inhibition activity against K562 and HeLa than those of the positive controls. The selectivity ratio of compounds 15h, 15d, and 15i were significantly higher than those of other active compounds, indicating that these three compounds had the lower hepatotoxicity. Several compounds displayed strong inhibition against leukemia cells. They inhibited tubulin polymerization, disrupted cellular microtubule networks by targeting the colchicine site, and promoted cell cycle arrest of leukemia cells at G2/M phase and cell apoptosis, as well as inhibiting angiogenesis. In summary, our research provided that novel synthesized N-aryl-2-trifluoromethyl-quinazoline-4-amine active derivatives as the inhibitors of tubulin polymerization in leukemia cells, which might be a valuable lead compounds for anti-leukemia agents.