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Human umbilical cord mesenchymal stem cell-derived exosomes inhibit inflammation and fibrotic scar formation after intracerebral hemorrhage.

Human umbilical cord mesenchymal stem cell-derived exosomes (hUCMSC-ex) have emerged as a promising alternative to whole-cell therapies due … f 200 μg. In vitro, primary astrocytes were treated with hUCMSC-ex and subsequently stimulated with Hemin (20 μmol/mL) to create a cellular model of cerebral hemorrhage. The expression levels of PTX3, TLR4/NF-κB/MMP3 pathway proteins, and inflammatory factors, including tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), and interleukin-10 …

Молекулярные модели, связанные с ущербом от митохондриала: нейроиммуномодуляторы в патофизиологии центральной нервной системы.

Нейроинфламмация способствует широкому спектру нейродегенеративных заболеваний, включая болезнь Альцгеймера, болезнь Паркинсона, болезнь Хантингтона и множественный склероз. Его движут неевропейские глиальные клетки, главным образом микроглии и астроциты. Микроглии являются постоянными иммунными клетками центральной нервной системы, в то время как астроциты являются основными элементами поддержки нейронных функций, но могут также участвовать в нейроиммунной реакции. Оба этих типа глиальных клеток могут стать реактивными при обнаружении определенных внутриклеточных молекул, которые появляются в

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… The effects of extracellular hemin in peripheral tissues are widely studied, as hemin is considered a DAMP due to its immunostimulatory effects (reviewed by Bozza and Jeney, 2020). Hemin is an agonist of multiple PRRs, with TLR4 being the most well defined. … While some hemin transporters have already been identified, elucidating the exact mechanism of trafficking extracellular hemin into CNS cells is necessary, as well as improving our understanding of how glial cells remove hemin from the brain parenchyma. …

Susceptibility of oral obligate anaerobes to telithromycin, moxifloxacin and a number of commonly used antibacterials.

INTRODUCTION: Obligate anaerobes are closely involved in the pathogenesis of oral and focal infections. The objective of this study was to evaluate the susceptibility profiles of obligate anaerobes of oral origin to telithromycin (TLM), moxifloxacin (MXF), and other antibiotics that are commonly used in dentistry. METHODS: The study sample comprised 172 obligate anaerobes isolated from the saliva of 43 adult volunteers. The minimum inhibitory concentrations (MICs) were determined by the agar dilution technique in Brucella agar medium supplemented with vitamin K, haemin and 5% (volume/volume)

1H NMR characterization of the solution active site structure of substrate-bound, cyanide-inhibited heme oxygenase from Neisseria meningitidis: comparison to crystal structures.

Heme oxygenase, HO, from the pathogenic bacterium Neisseria meningitidis catabolizes heme for the iron necessary for infection. The enzyme, labeled HemO, exhibits less sequence homology to mammalian HO than another studied HO from Corynebacterium diphtheriae. Solution 1H NMR has been utilized to define the active site molecular and electronic structure of the cyanide-inhibited, substrate-bound complex for comparison with those provided by several crystal structures. Extensive assignments by solely 1H NMR 2D methods reveal a structure that is very strongly conserved with respect to the crystal

LmrR: A Privileged Scaffold for Artificial Metalloenzymes.

The biotechnological revolution has made it possible to create enzymes for many reactions by directed evolution. However, because of the imm … nthroline was successful in Friedel-Crafts alkylation reactions, giving rise to up to 94% ee. Also, hemin was bound, resulting in an artificial heme enzyme for enantioselective cyclopropanation reactions. The importance of structural dynamics of LmrR was suggested by computational studies, which showed that the pore can open up to allow access of substr …

DhHP-6 ameliorates hepatic oxidative stress and insulin resistance in type 2 diabetes mellitus through the PI3K/AKT and AMPK pathway.

Insulin resistance is one major features of type 2 diabetes mellitus (T2DM). Deuterohemin-βAla-His-Thr-Val-Glu-Lys (DhHP-6), a novel microperoxidase mimetic designed and synthesized based on microperoxidase 11 (MP-11), can scavenge reactive oxygen species (ROS) in vivo. In our previous studies, we showed that oral DhHP-6 could reduce blood glucose and improve insulin resistance. To investigate the mechanisms of how DhHP-6 ameliorates oxidative stress and insulin resistance, we established T2DM mouse models and glucosamine-induced HepG2 cell insulin resistance models. The results suggested that…

Cytochrome c catalyses the formation of pentyl radical and octanoic acid radical from linoleic acid hydroperoxide.

A reaction of 13-hydroperoxide octadecadienoic acid (13-HPODE) with cytochrome c was analysed using ESR, HPLC-ESR and HPLC-ESR-MS by the combined use of the spin-trapping technique. The ESR, HPLC-ESR and HPLC-ESR-MS analyses showed that cytochrome c catalyses formation of pentyl and octanoic acid radicals from 13-HPODE. On the other hand, only the alpha-(4-pyridyl-1-oxide)-N-t-butylnitrone/octanoic acid radical adduct was detected in the elution profile of HPLC-ESR for a mixture of 13-HPODE with haematin, indicating that haematin catalyses the formation of octanoic acid radical. In addition, t

Cryptic polyreactivity of IgG expressed by splenic marginal zone B-cell lymphoma.

Polyreactive antibodies represent a significant fraction of immune repertoires and play an important role in the immune defense and immune homeostasis. Polyreactive B-cell receptors (BCR), however, are frequently expressed by B-cell lymphomas. It was suggested that polyreactive BCR on lymphoma cells might deliver stimulation signals by binding to various endogenous or exogenous antigens, thus promoting the survival of the malignant cells. In addition to natural polyreactive antibodies, immune repertoires contain antibodies that acquire polyreactivity after exposure to different redox-active su

Transcriptional regulation of 5-aminolevulinate synthase by phenobarbital and cAMP-dependent protein kinase.

5-Aminolevulinate synthase (ALA-S) is a mitochondrial matrix enzyme that catalyzes the first and rate-limiting step of the heme biosynthesis. There are two ALA-S isozymes encoded by distinct genes. One gene encodes an isozyme that is expressed exclusively in erythroid cells, and the other gene encodes a housekeeping isozyme that is apparently expressed in all tissues. In this report we examine the mechanisms by which phenobarbital and cAMP regulate housekeeping ALA-S expression. We have determined that cAMP and phenobarbital effects are additive and the combined action is necessary to observe

Costoclavicular pinching: a complication of long-term central venous catheters. A report of three cases.

In the course of 1994-1995 we found three nearly identical cases involving fracture of polyurethane catheters from subcutaneous implantable vascular ports. This resulted in complications: leakage of drugs and infusions and thereby soft tissue damage. The leakage occurred in the costoclavicular space in all instances. We assume that the catheters have been subjected to repeated pinching, resulting in material fatigue. In order to eliminate the risk of this serious complication, the subclavian route should be avoided and preference given to the approach via the internal jugular vein.

Fetal hemoglobin induction during decitabine treatment of elderly patients with high-risk myelodysplastic syndrome or acute myeloid leukemia: a potential dynamic biomarker of outcome.

Hematologic responses to hypomethylating agents are often delayed in patients with myelodysplastic syndrome or acute myeloid leukemia. Fetal hemoglobin is a potential novel bio-marker of response: recently, we demonstrated that a high fetal hemoglobin level prior to decitabine treatment was associated with superior outcome. Here we investigated whether early fetal hemoglobin induction during decitabine treatment also had prognostic value, and studied the potential of decitabine to induce erythroid differentiation and fetal hemoglobin expression in vitro Fetal hemoglobin levels were measured by

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… Transcriptome profiling by mRNA expression arrays in K562 cells revealed the greatest similarity between hemin-and decitabine-treated cells ( Figure 6A,B ). … Here, a similar DNA methylation analysis of K562 cells treated with hemin instead of decitabine would address this “cause or consequence” question. …

Effectiveness of synthetic trioxolane OZ78 against Schistosoma japonicum in mice and rabbits.

Antischistosomal activities of a synthetic peroxide OZ78 (an ozonide carboxylic acid) against Schistosoma japonicum have been studied in mic … histosomula, and day 35 adult schistosomes. But OZ78 and OZ78-Na salt 10 and 20 μg/mL together with hemin 80 μg/mL showed decrease in worm motor activity and severe damage to the worm tegument and intestine, and all worms died within 3 days post-incubation. After infected mice were treated orally with OZ78 at a single dose of 400 mg/kg for 1 day, 34.9% …

Inhibition of MALAT1 facilitates ROS accumulation via the Keap1/HO-1 pathway to enhance photodynamic therapy in secondary hyperparathyroidism.

The prevalence of secondary hyperparathyroidism (SHPT) in advanced chronic kidney disease (CKD) exceeds 80 %. Our previous study indicated that photodynamic therapy (PDT) has potential for treating SHPT. Long noncoding RNA (lncRNA) is involved in various oxidative stress and apoptotic processes, but the molecular mechanism remains unreported. In this study, we found that PDT induced apoptosis in SHPT through reactive oxygen species (ROS) accumulation. The expression of metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) and heme oxygenase 1 (HO-1) within SHPT was upregulated after

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… Hemin is an effective HO-1 inducer, and western blotting confirmed that the protein level of HO-1 increased accordingly with the increase of Hemin concentration ( Fig. 4 F– sFig. 2B ), as well as the siRNAs of HO-1 were effective in interfering with its expression level ( Fig. 4 G– sFig. 2C ). … Hemin enhances the cardioprotective effects of mesenchymal stem cell-derived exosomes against infarction via amelioration of cardiomyocyte senescence. J. Nanobiotechnol. 2021;19(1):332. doi: 10.1186/s12951-021-01077-y. 27. …

Heme oxygenase-1 protects human periodontal ligament cells against substance P-induced RANKL expression.

BACKGROUND AND OBJECTIVE: Although substance P (SP) stimulates bone resorption activity and this is reported to be correlated with the degree of periodontal inflammation, it is unclear how human periodontal ligament cells regulate neuropeptide-induced osteoclastogenesis or the possible involvement of heme oxygenase-1 (HO-1) might be. This study examines how SP affects osteoprotegerin (OPG) and RANKL expression via HO-1. MATERIAL AND METHODS: Using immortalized human periodontal ligament cells, the effects of SP on the expression of HO-1, RANKL and OPG mRNA and proteins were determined by RT-P

Identification of a two-component signal transduction system from Corynebacterium diphtheriae that activates gene expression in response to the presence of heme and hemoglobin.

Corynebacterium diphtheriae, the causative agent of diphtheria, utilizes various host compounds to acquire iron. The C. diphtheriae hmuO gene encodes a heme oxygenase that is involved in the utilization of heme and hemoglobin as iron sources. Transcription of the hmuO gene in C. diphtheriae is controlled under a dual regulatory mechanism in which the diphtheria toxin repressor protein (DtxR) and iron repress expression while either heme or hemoglobin is needed to activate transcription. In this study, two clones isolated from a C. diphtheriae chromosomal library were shown to activate transcri

The Neisseria meningitidis haemoglobin receptor: its role in iron utilization and virulence.

The Neisseria meningitidis haemoglobin receptor gene, hmbR, was cloned by complementation in a porphyrin-requiring Escherichia coli mutant. hmbR encodes an 89.5 kDa outer membrane protein which shares amino acid homology with the TonB-dependent receptors of Gram-negative bacteria. HmbR had the highest similarity to Neisseria transferrin and lactoferrin receptors. The utilization of haemoglobin as an iron source required internalization of the haemin moiety by the cell. The mechanism of haemin internalization via the haemoglobin receptor was TonB-dependent in E. coli. A N. meningitidis hmbR mut

First Report of Ratoon Stunt of Sugarcane Caused by Leifsonia xyli subsp. xyli in Pakistan.

Sugarcane (Saccharum hybrids), the second largest cash crop of Pakistan, is planted on 1.029 million ha with an annual production of 50 mill … ·7H2O, 0.5 g of glucose, 1 g of cysteinefree base, 2 g of bovine serum albumin, and 15 mg of bovine hemin chloride) and incubated for 3 to 4 weeks at 28°C. Light, off-white, round, and raised growth bacterial colonies (1.5 to 4.5 × 0.2 to 0.35 μm). Isolates were positive for the gram and catalase reactions and negative for oxidase, aesculin hydrolysis, …

Новые клеточные модели для изучения взаимодействия Мьелин и Микроглиа.

Множественный склероз (MS) характеризуется обезвоживанием и нейроинфламмацией, при этом окислительный стресс играет ключевую роль в патологии поражения. Цель этого исследования заключалась в изучении дифференциальной реакции клеток на миелиновый мусор в различных окислительных состояниях. Окисление Myelin было вызвано с помощью системы Cuperoxid, что подтверждается повышенными уровнями TBARS и автофлюоресценцией. Из-за воздействия миелина на жизнеспособность микроглии BV-2 так и не была затронута. Однако окисленный миелин значительно изменил маркеры окислительного стресса, автофагию и метаболи

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… In this regard, in a more complex model employing myelinating cell culture (in which neurons, astroglia, microglia, and oligodendroglia are co-cultures), the addition of hemin to the cell media triggers myelin oxidation and ferroptosis. … Interestingly, they found that the cytotoxic effects of hemin treatment were microglia-independent, although these cells secreted several pro-inflammatory cytokines into the cell medium [ 20 ]. …

Porphyromonas gingivalis усугубляет экспериментальный аутоиммунный энцефаломиэлит, проводя дифференциацию TH1 с помощью сигнала ZAP70/NF-IB.

Множественный склероз (MS) характеризуется хроническим воспалением и обезвоживанием в центральной нервной системе (CNS), главным образом в результате ненормальной активации периферической иммунной системы, в частности клеток TH1. Как основной патоген в периодонтрите, Porphyromonas gingivalis (P. gingivalis) связан с повышенным риском множественных склерозных прогрессий; однако его роль в центральной нервной системе воспаления остается неясной. В этом исследовании мы стремились определить, поощряет ли P. gingivalis периферическую дифференциацию клеток TH1 по сигнальному маршруту ZAP70/NF-InB, т

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… Bacterial culture P. gingivalis (strain W83, BNCC) was cultured on enriched sterile blood agar consisting of 3.7% brain heart infusion (BHI) agar, 2% agarose, 0.05% cysteine, 0.0005% hemin, 0.0001% menadione, and 5%–7% defibrinated sheep blood, under anaerobic conditions generated by an AnaeroPack. … After 4–5 days of incubation, a single colony was transferred to BHI broth containing 3.7% BHI, 0.0005% hemin, 0.0001% menadione, and 0.05% cysteine, and cultured for an additional 48 h. …