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Mcgowan posted an update 1 year, 1 month ago
Maternal subclinical hypothyroidism (SCH) during pregnancy can adversely affect the neurodevelopment of the offspring. The balance of nerve growth factor (NGF)-related tropomyosin receptor kinase A/p75 neurotrophin receptor (TrkA/p75NTR) signaling in the hippocampus is important in brain development, and whether it affects cognitive function in maternal SCH’s offspring is not clear. In this study, we found that compared with the control (CON) group, expression of proliferation-related proteins [NGF, p-TrkA, phospho-extracellular signal-regulated kinase 1/2 (p-ERK1/2) and phospho-cAMP response element-binding protein (p-CREB)] decreased in the hippocampus of the offspring in the SCH group, overt hypothyroidism (OHT) group, and the group with levothyroxine (L-T4) treatment for SCH from gestational day 17 (E17). In contrast, expression of apoptosis-related proteins [pro-NGF, p75NTR, phospho-C-Jun N-terminal kinase (p-JNK), p53, Bax and cleaved caspase-3] was increased. The two groups with treatment with L-T4 for SCH from E10 and E13, respectively, showed no significant difference compared with the CON group. L-T4 treatment enhanced relative expression of NGF by increasing NGF/proNGF ratio in offspring from maternal SCH rats. In conclusion, L-T4 treatment for SCH from early pregnancy dramatically ameliorated cognitive impairment via TrkA/p75NTR signaling, which involved activation of the neuronal proliferation and inhibition of neuronal apoptosis in SCH rats’ offspring.Neutrophil extracellular traps (NETs) are networks of decondensed chromatin loaded with antimicrobial peptides and enzymes produced against microorganisms or biochemical stimuli. Since their discovery, numerous studies made separately have revealed multiple triggers that induce similar NET morphologies allowing to classify them as lytic or non-lytic. However, the variability in NET composition depending on the inducer agent and the local milieu under similar conditions has been scarcely studied. In this work, a comparative study was conducted to evaluate structural and enzymatic divergences in NET composition induced by biochemical (phorbol myristate acetate [PMA] and hypochlorous acid [HOCl]) and microbiologic (Candida albicans, Staphylococcus aureus, and Pseudomonas aeruginosa) stimuli, along with the presence of plasma from healthy donors or patients with systemic lupus erythematosus (SLE). The results showed a differential composition of DNA and the antimicrobial peptide cathelicidin (LL37) and a variable enzymatic activity (neutrophil elastase, cathepsin G, myeloperoxidase) induced by the different stimuli despite showing morphologically similar NETs. Additionally, SLE plasma´s presence increased DNA and LL37 release during NET induction independently of the trigger stimulus but with no enzymatic activity differences. This work provides new evidence about NET composition variability depending on the inducer stimulus and the local milieu.Unique bacterial associations were formed in the polluted soils from territory of the industrial factories Open Joint Stock Company “The Middle Volga Chemical Plant,” Chapaevsk, Russia and Open Joint Stock Company “Lubricant Producing Plant,” Perm, Russia. RGD(Arg-Gly-Asp)Peptides ic50 This study evaluates the influence of the biphenyl/polychlorinated biphenyls (PCB) on the formation of aerobic bacterial associations and their biodegradative potential. Enrichment cultivation of the soil samples from the territories of these industrial factories with PCB (commercial mixture Sovol) was lead for forming aerobic bacterial enrichment cultures showing a unique composition. The dominating in these bacterial cultures was the phylum Proteobacteria (Beta- and Gammaproteobacteria). Using biphenyl as a carbon source led to decrease of biodiversity in the final stable bacterial associations. Periodic cultivation experiments demonstrated that the association PN2-B has a high degradative potential among the six studied bacterial associations. PN2-B degraded 100% mono-chlorobiphenyls (94.5 mg/L), 86.2% di-chlorobiphenyls (22.3 mg/L), 50.9% Sovol, and 38.4% Delor 103 (13.8 mg/L). Qualitative analysis of metabolites showed that association performed transformation of chlorobenzoic acids (PCB degradation intermediates) into metabolites of citrate cycle. Twelve individual strain-destructors were isolated. The strains were found to degrade 17.7-100% PCB1, 36.2-100% PCB2, 18.8-100% PCB3 (94.5 mg/L), and 15.7-78.2% PCB8 (22.3 mg/L). The strains were shown to metabolize chlorobenzoic acids formed during degradation of chlorobiphenyls. A unique ability of strains Micrococcus sp. PNS1 and Stenotrophomonas sp. PNS6 to degrade ortho-, meta-, and para-monosubstituted chlorobenzoic acids was revealed. Our results suggest that PN2-B and individual bacterial strains will be perspective for cleaning of the environment from polychlorinated biphenyls.Under normal physiological conditions, IGF-1 (insulin-like growth factor-1) has important biological effects. However, many studies have found that IGF-1 is closely related to the occurrence and development of breast cancer. But up to now, the cellular properties of IGF-1 have not been systematically explored in breast cancer cell. It is well-known that the cellular properties and behaviors of IGF-1/IGF-1R are closely related to its biological functions. In the current study, we used the breast cancer cell line as a model to explore the biological characteristics of IGF-1/IGF-1R, and found that IGF-1/IGF-1R can be internalized into the cytoplasm. In addition, we also found that IGF-1R can also enter cell nuclei under the mediation of IGF-1. Further research found that the nuclear-localized IGF-1R has important potential biological effects, which is closely associated to the proliferation of breast cancer cell, this may be achieved by regulating IGF-1R-mediated intracellular signaling. The current research has laid the foundation for investigating the relationship between IGF-1/IGF-1R system and the occurrence and development of breast cancer.Abdominal massage (AM), a traditional Chinese medicine-based treatment method, has received considerable attention in the recent years. The aim of the present study was to investigate the effect of AM on high-fat diet (HFD)-induced insulin resistance (IR) in comparison with resveratrol (RSV) treatment. Forty-eight male Sprague-Dawley rats were randomly divided into the following four groups standard chow diet (control group), high-fat diet (model group), HFD + abdominal massage (AM group), and HFD + resveratrol (RSV group). A rat model of IR was established by feeding HFD to rats for 8 weeks followed by treatment with AM or RSV for 4 weeks. The underlying HFD-induced IR molecular mechanisms were studied in rat serum and skeletal muscles. RSV and AM significantly improved glucose intolerance, hyperglycemia, obesity, and significantly reduced lipid accumulation [triglyceride (TC), total cholesterol (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C)], adipocytokine [free fatty acids (FFA), adiponectin (ADPN)] and serum pro-inflammatory cytokines (IL-6 and TNF-α) secretion.