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Лазерно-приводимые кортики в мышах в качестве модели прогрессивной многоклерозной патологии.

Справочная информация: В нынешних моделях склероза (MS) для животных основное внимание уделяется воспалению белой материи, отражающему раннее заболевание. Однако прогрессивные MS (PMS) характеризуются кортикальной патологией, включая подпиальное демиэлирование, хроническое менингеальное воспаление и микроглиальную активацию, которые недопредставлены в существующих моделях. В то время как альтернативные модели мыши воспроизводят релапсирующий фенотип и серую патологию материи, патология часто рассеивается по мозгу, что осложняет анализ конкретных участков поражения. Методы: Для устранения этого

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… Tissue Processing The mice were euthanized using an overdose of sodium pentobarbital (100 mg/kg, Glostrup Apotek, Glostrup, Denmark) injected intraperitoneally, and perfused transcardially with ice-cold PBS before brain isolation. …

Treatment of Refractory Convulsive Status Epilepticus: A Comprehensive Review by the American Epilepsy Society Treatments Committee.

PURPOSE: Established tonic-clonic status epilepticus (SE) does not stop in one-third of patients when treated with an intravenous (IV) benzo … ldren and adults using IV brivaracetam, ketamine, lacosamide, levetiracetam (LEV), midazolam (MDZ), pentobarbital (PTB; and thiopental), propofol (PRO), and valproic acid (VPA). Adrenocorticotropic hormone (ACTH), corticosteroids, intravenous immunoglobulin (IVIg), magnesium sulfate, and pyridoxine were added to determine the effectiveness in treating hard-to-c …

Adenosine A2A receptor-mediated interactions between Th1+ T cells and the choroid plexus epithelium via IFN-γ signalling control T-Cell infiltration in experimental autoimmune encephalomyelitis.

BACKGROUND: Adenosine A2A receptor (A2AR) antagonists have been consistently demonstrated to protect against multiple sclerosis (MS) pathology, but A2AR knockout (A2AR-/-) mice exhibit exacerbated immune injury, raising concerns regarding the use of A2AR antagonists for MS treatment. Here, we revealed the critical involvement of A2AR-mediated interactions between Th1+ T cells and the choroid plexus (ChP) epithelium in the pathology of experimental autoimmune encephalomyelitis (EAE). METHODS: We assessed the effects of A2AR knockout on ChP gateway activity and the interferon gamma (IFN-γ)-secr

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… Isolation of the ChP The mice were deeply anaesthetized with 1% pentobarbital sodium, followed by perfusion with prechilled sterile PBS. The entire brain was then carefully dissected. … Analysis of IFN-γ levels by enzyme-linked immunosorbent assay (ELISA) On the 14th day following EAE induction, the mice were anaesthetized with 1% pentobarbital sodium for the purpose of isolating peripheral blood. …

Artificial Neural Networks Coupled with MALDI-TOF MS Serum Fingerprinting To Classify and Diagnose Pathological Pain Subtypes in Preclinical Models.

Pathological pain subtypes can be classified as either neuropathic pain, caused by a somatosensory nervous system lesion or disease, or nociplastic pain, which develops without evidence of somatosensory system damage. Since there is no gold standard for the diagnosis of pathological pain subtypes, the proper classification of individual patients is currently an unmet challenge for clinicians. While the determination of specific biomarkers for each condition by current biochemical techniques is a complex task, the use of multimolecular techniques, such as matrix-assisted laser desorption/ioniza

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… Peripheral neuropathic pain was induced in mice by the ligation of the sciatic nerve performed in accordance with procedures described elsewhere. 51 , 70 Briefly, animals were first anesthetized with sodium pentobarbital (50 mg/kg, i.p.), and an incision was made in the right thigh exposing the sciatic … Sample Collection and Preparation for MS Analysis At the end of the experimental protocol, all the animals were anesthetized with sodium pentobarbital (90 mg/kg; i.p.), and blood was collected through the insertion of an intracardiac needle. …

Study on the therapeutic effect of glucocorticoids on acute kidney injury in rats exposed to diquat.

AIMS: To preliminarily explore, whether glucocorticoids have a therapeutic effect on diquat-induced acute kidney injury in rats. METHOD: 15 … d 21 d after exposure. The rats were sacrificed by an intraperitoneal injection of 100 mg/kg sodium pentobarbital overdose. Blood was collected by puncture of the inferior vena cava, used to determine Cr and BUN. The upper segment of the left kidney was collected for histopathological examination. Elisa was used to detect neutrophil gelatinase-associated lipoca …

Диметилфумарат уменьшает травму от печени ишемии и реперуляции путем подавления сигнала CGAS-STING.

Повреждение печени во время периоперационной фазы операции на печени часто происходит в результате печени. Неправильная активация сигнала СТИНГ может вызвать чрезмерную воспламенение реакции на усугубление печени. Диметилфумарат (DMF) — разрешенный УЛХ иммунодулятор, используемый для лечения множественного склероза и псориаза в силу его заметных свойств против воспаления. Однако механизм и целевые показатели ДМФ в области иммуномодуляции остаются неясными. Здесь мы обнаружили, что DMF подавляет активацию CGAS-STING, индуцируемую HSV-1, ДНК яичек и митохондриальная ДНК в различных клетках. DMF

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… Mouse hepatic I/R injury model establishment We employed a well‐documented rodent model for 70% hepatic I/R injury. 39 Under this protocol, mice were first sedated with an intraperitoneal administration of 1% pentobarbital. In the control group, no liver ischemia was induced. …

Бета Адренергическая сигнализация как терапевтическая цель для автономного иммунитета.

Мы недавно определили молекулярный механизм с использованием бета-адренергических рецепторов 1 и 2 (β1/2) при разработке лимфоцитов TH17. Фармакологические и генетические ингибиции этих рецепторов в сочетании, но не отдельно, сказались на способности Т-лимфоцитов производить профламматический интерleукин 17А (IL-17A) и вместо этого способствовали производству защитных клеток Трега, которые скрывают инфлюкин-10 (IL-10). Вместе с тем остается неясным, может ли этот механизм регулирования использоваться в качестве нового терапевтического подхода к аутоиммунным расстройствам при посредничестве Т-л

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… Mice were sacrificed by pentobarbital overdose (150mg/kg, Fatal Plus, Vortech Pharmaceuticals, Dearborn, MI, USA) administered intraperitoneally. All mice were sacrificed between 7:00am and 9:00am Central Time to eliminate circadian rhythm effects on T-lymphocyte function. …

Наркотики, основанные на сходстве генных экспрессионных сигнатур, чтобы исследовать потенциальные признаки кексетина: тематическое исследование множественных склерозов.

Quercetin (QR) — природный флавонол, широко распространенный в королевстве растений с обширными фармакологическими последствиями. Чтобы найти потенциальные клинические показатели QR, 156 Дифференциально выраженные гены (DEG), регулируемые QR, были получены из базы данных Gene Express Omnibus, и новые потенциальные фармакологические эффекты и клинические показатели QR были перенаправлены путем интегрирования соединений с аналогичными генными сигнатурами возмущения и соответствующими сигнатурами болезни QR на основе карты связи и платформ Coexedia. Предлагаемые результаты QR оказывают главным об

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… The mice were anesthetized with 1% pentobarbital sodium and perfused with 0.9% sodium chloride solution on day 21 p.i. …

Construction of a Novel Necroptosis-Related Signature in Rat DRG for Neuropathic Pain.

BackgroundRecent studies have shown necroptosis may play a role in the development of inflammation-associated pain. However, research on the correlation between necroptosis-related genes and neuropathic pain in the dorsal root ganglia (DRG) is limited. This study aims to identify a gene signature related to necroptosis in DRG that can predict neuropathic pain.MethodsThe mRNA expression profiles associated with neuropathic pain (GSE24982 and GSE30691) were acquired from the Gene Expression Omnibus (GEO) database. The Least Absolute Shrinkage and Selection Operator (Lasso) and Support Vector Mac

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… Under deep anesthesia (sodium pentobarbital, 10–20 mg/kg, i.p)., the L4 DRG of about 25 g adult male mouse were accessed by removing transverse processes of the vertebrae. …

Prevention of tooth extraction-triggered bisphosphonate-related osteonecrosis of the jaws with basic fibroblast growth factor: An experimental study in rats.

Osteonecrosis of the jaw induced by administration of bisphosphonates (BPs), BP-related osteonecrosis (BRONJ), typically develops after tooth extraction and is medically challenging. As BPs inhibit oral mucosal cell growth, we hypothesized that suppression of the wound healing-inhibiting effects could prevent BRONJ onset after tooth extraction. Since basic fibroblast growth factor (bFGF) promotes wound healing, but has a short half-life, we examined whether the initiation of BRONJ could be prevented by applying a bFGF-containing gelatin hydrogel over the extraction sockets of BRONJ model rats.

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… After induction of anesthesia with a single intraperitoneal injection of pentobarbital sodium 50 mg/kg, extraction of the unilateral lower first molar was performed in each rat ( Fig 1 ). …

miR-21 regulates osteogenic and adipogenic differentiation of BMSCs by targeting PTEN.

ObjectiveTo explore the effects and mechanism of miR-21 on the osteogenic/adipogenic differentiation of mouse BMSCs.MethodsThe bilateral ovaries of C57BL/6J mice (n=24) were removed to construct an osteoporosis model. Real-time quantitative polymerase chain reaction (qRT-PCR) was used to detect the expression of miR-21, osteogenic/adipogenic genes, and PTEN. ALP and ARS and ORO staining were used to detect the formation of calcium nodules and lipid droplets in BMSCs. Western blot was used to detect the expression of PTEN.ResultsmiR-21 was significantly down-regulated in osteoporotic mice. The

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… Before surgery, mice were fasted for 12 h and injected intraperitoneally with 1% pentobarbital. The mice in the model group were performed bilateral ovarian dissection through the dorsal approach. …

Colorectal cancer cells promote osteoclastogenesis and bone destruction through regulating EGF/ERK/CCL3 pathway.

Bone metastasis of colorectal cancer (CRC) cells leads to osteolysis. Aberrant activation of osteoclasts is responsible for bone resorption in tumor. In general, bone marrow-derived monocytes (BMMs) differentiate into osteoclasts, however, how CRC cells interact with BMMs and how to regulate the differentiation is elusive. We here report that CRC cells promote bone resorption in bone metastasis. Transcriptomic profiling revealed CCL3 up-regulated in MC-38 conditional medium treated BMMs. Further investigation demonstrated that CCL3 produced by BMMs facilitated cell infusion and thus promoted t

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… Anesthesia was performed before procedures through intraperitoneally infection of 0.5% pentobarbital sodium solution. The mice were killed by CO 2 inhalation. All experiments conformed to the guidelines of the ethical use of animals, all efforts were made to reduce the number of animals used. …

Silencing of SPARC represses heterotopic ossification via inhibition of the MAPK signaling pathway.

Heterotopic ossification (HO), the pathologic formation of extraskeletal bone, can be disabling and lethal. However, the underlying molecular mechanisms were largely unknown. The present study aimed to clarify the involvement of secreted protein acidic and rich in cysteine (SPARC) and the underlying mechanism in rat model of HO. The mechanistic investigation on roles of SPARC in HO was examined through gain- and loss-of-function approaches of SPARC, with alkaline-phosphatase (ALP) activity, mineralized nodules, and osteocalcin (OCN) content measured. To further confirm the regulatory role of S

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… Rats were anesthetized with an intraperitoneal injection of 30 μg/g pentobarbital under aseptic conditions. The left crus posterolateral approach was used. …

Preclinical Evaluation of a Lentiviral Vector for Huntingtin Silencing.

Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder resulting from a polyglutamine expansion in the huntingtin (HTT) protein. There is currently no cure for this disease, but recent studies suggest that RNAi to downregulate the expression of both normal and mutant HTT is a promising therapeutic approach. We previously developed a small hairpin RNA (shRNA), vectorized in an HIV-1-derived lentiviral vector (LV), that reduced pathology in an HD rodent model. Here, we modified this vector for preclinical development by using a tat-independent third-generation LV (pCCL) ba

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… Histological Processing Eight weeks after lentiviral injection, animals received an overdose of sodium pentobarbital and were transcardially perfused with PBS followed by 4% paraformaldehyde (Fluka; Sigma) and 10% picric acid fixation. … Mice were sacrificed by pentobarbital overdose 24 hr or 6 weeks after bilateral infection of each siRNA construct or PBS in the striatum. Brains were dissected, placed on ice, and sliced using a mouse brain matrix into 1-mm-thick fresh sections. …

Low-level laser therapy prevents medication-related osteonecrosis of the jaw-like lesions via IL-1RA-mediated primary gingival wound healing.

BACKGROUND: Medication-related osteonecrosis of the jaw (MRONJ) is a serious debilitating disease caused by anti-resorption and anti-angiogenesis drugs, significantly affecting patients' quality of life. Recent studies suggested that primary gingival wound healing may effectively prevent the development of MRONJ. This study aimed to evaluate the effects of low-level light therapy (LLLT) on promoting gingival wound healing in extraction sockets of MRONJ-like mice and preventing the occurrence of MRONJ. Furthermore, we explored underlying mechanisms. METHODS: Mice were randomly divided into the

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… After two weeks of drug treatment, tooth extraction of bilateral maxillary second molars was performed under general anesthesia using pentobarbital (50 mg/kg, P3761, Sigma, USA). The ctrl group or the Zol group received no local treatment for tooth sockets after tooth extraction. …

MM-129 as a Novel Inhibitor Targeting PI3K/AKT/mTOR and PD-L1 in Colorectal Cancer.

Background and aimsThe purpose of the present study was to examine the pharmacodynamics features of MM-129 (1,2,4-triazine derivative) as a novel promising drug candidate against colon cancer.MethodsMM-129 was assessed for antitumor activity through an in vivo study on Cby.Cg-Foxn1nu/cmdb mice. The mechanistic studies investigated cellular affinity of a new 1,2,4-triazine derivative by measuring levels of intracellular/extracellular signal molecules participating in tumorigenesis.ResultsThe results revealed that MM-129 significantly reduced tumor growth in mice challenged with DLD-1 and HT-29

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… Animals were euthanized by an overdose of pentobarbital administered intraperitoneally. 2.2. …

Targeting Notch-1 positive acute leukemia cells by novel fucose-bound liposomes carrying daunorubicin.

Complete remission by induction therapy in acute myelogenous leukemia (AML) can be achieved due to improvements in supportive and optimized therapy. However, more than 20% of patients will still need to undergo salvage therapy, and most will have a poor prognosis. Determining the specificity of drugs to leukemia cells is important since this will maximize the dose of chemotherapeutic agents that can be administered to AML patients. In turn, this would be expected to lead to reduced drug toxicity and its increased efficacy. We targeted Notch-1 positive AML cells utilizing fucose-bound liposomes

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… All surgery was performed under sodium pentobarbital anesthesia, and all efforts were made to minimize suffering. All mice underwent euthanasia when tumor volumes reached 20 mm in diameter. Statistics Results are presented as mean ± standard deviation (SD) for each sample. …

Euthanasia and physician-assisted suicide not meeting due care criteria in the Netherlands: a qualitative review of review committee judgements.

UNLABELLED: ObjectivesTo assess how Dutch regional euthanasia review committees (RTE) apply the euthanasia and physician-assisted suicide (EAS) due care criteria in cases where the criteria are judged not to have been met ('due care not met' (DCNM)) and to evaluate how the criteria function to set limits in Dutch EAS practice. DESIGN: A qualitative review using directed content analysis of DCNM cases in the Netherlands from 2012 to 2016 published on the RTE website (https://www.euthanasiecommissie.nl/) as of 31 January 2017. RESULTS: Of 33 DCNM cases identified (occurring 2012-2016), 32 case

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… the patient to obtain backup meds, then administered the neuromuscular blocker without a second coma inducer, despite evidence that the patient was not in a full coma. 2016-23 | Medical care | A man, 80–90 years old, with Alzheimer’s disease | The physician used a phenobarbital beverage instead of pentobarbital …

Curcumol inhibits the malignant progression of prostate cancer and regulates the PDK1/AKT/mTOR pathway by targeting miR‑9.

Curcumol has been reported to exert anti‑tumor activity, but its intrinsic molecular mechanism in prostate cancer remains to be elucidated. The present study aimed to analyze the effect of curcumol on prostate cancer and identify its possible internal regulatory pathway using in vitro cell culture and in vivo tumor model experiments. The cytotoxicity of curcumol was detected using a Cell Counting Kit‑8 assay and it was found that curcumol had no obvious toxicity or side effects on RWPE‑1 cells. Wound healing, Transwell and flow cytometry assays demonstrated that curcumol could affect the activ

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… When the maximum tumor volume reached 2,000 mm 3 , the mice were sacrificed via an intraperitoneal injection of pentobarbital sodium (150 mg/kg). The tumor was removed to prepare for further experiments. …

Гастродин поощряет миелиогенез CNS и смягчает демиелионирующее повреждение путем активации сигнала PI3K/AKT/mTOR.

Демиелинция является общей особенностью многочисленных неврологических расстройств, включая множественный склероз и лейкодистрофию. Хотя миелин может быть регенерирован самопроизвольно после травмы, этот процесс зачастую является неадекватным, что может привести к нейродегенерации и обострению неврологической дисфункции. Ряд наркотиков, направленных на содействие дифференциации клеток-прекурсоров олигодендроцитов (ОПК), привели к неудовлетворительным клиническим последствиям. В одном из недавних исследований стратегия дифференциации в пользу ОПС была переориентирована на укрепление миелиногене

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… We anesthetized mice with pentobarbital, and then the whole brains or spinal cords were collected following transcardial perfusion and overnight post-fixation with 4% paraformaldehyde. Adult zebrafish were husbandry in a recirculating system with a 14:10 light-dark cycle at 28 ± 1 °C [ 24 , 25 ]. …