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Dendrimer-doxorubicin conjugates exhibit improved anticancer activity and reduce doxorubicin-induced cardiotoxicity in a murine hepatocellular carcinoma model.

Hepatocellular carcinoma (HCC) is the 2nd leading cause of cancer-related deaths every year globally. The most common form of treatment, hepatic arterial infusion (HAI), involves the direct injection of doxorubicin (DOX) into the hepatic artery. It is plagued with limited therapeutic efficacy and the occurrence of severe toxicities (e.g. cardiotoxicity). We aim to improve the therapeutic index of DOX delivered via HAI by loading the drug onto generation 5 (G5) poly(amidoamine) (PAMAM) dendrimers targeted to hepatic cancer cells via N-acetylgalactosamine (NAcGal) ligands. DOX is attached to the

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… Mice were anesthetized at 4–5% isoflurane for induction and reduced to 2–3% for maintenance during the procedure, with the carrier gas being oxygen. … Mice were anesthetized with 1.25–2% isoflurane in 1 L/min of oxygen. Animals were then placed in the supine position and imaged at 7T using a Direct Drive console (Agilent Technologies, Santa Clara, CA) and a 40 mm inner diameter transmit-receive volume coil (Morris Instruments, Ontario, Canada). …

Кетогенные изменения в метаболизме печени с потенциальными последствиями для озанимодных фармакокинетических мышей.

Кетогенное питание (КД) все чаще рассматривается в качестве адъюнктивного терапевтического подхода к целому ряду заболеваний, однако его воздействие на фармакокинетику сопутствующих лекарств остается неясным. Такое взаимодействие может иметь особое значение в случае множественного склероза, когда КД изучается в качестве дополнительной стратегии наряду с лечением заболеваний, например, озанимодом. Поэтому мы изучили вопрос о том, влияет ли KD на озанимодный метаболизм и фармакокинетику, и изучили потенциальные факторы, которые могут способствовать такому воздействию. Женщинам, не содержащим пат

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… Mice were euthanized by isoflurane overdose, followed by cervical dislocation. Blood samples were collected by cardiac puncture through both atria into syringes coated with 0.5 mol/L EDTA (pH 8). Livers, without gallbladders, were removed and stored at −80 °C. …

Rack1-mediated ferroptosis affects hindgut development in rats with anorectal malformations: Spatial transcriptome insights.

Anorectal malformation (ARM), a common congenital anomaly of the digestive tract, is a result of insufficient elongation of the urorectal septum. The cytoplasmic protein Receptor of Activated C-Kinase 1 (Rack1) is involved in embryonic neural development; however, its role in embryonic digestive tract development and ARM formation is unexplored. Our study explored the hindgut development and cell death mechanisms in ARM-affected rats using spatial transcriptome analysis. We induced ARM in rats by administering ethylenethiourea via gavage on gestational day (GD) 10. On GDs 14-16, embryos from b

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… From GDs 14–16, the pregnant rats were anaesthetised using isoflurane inhalation combined with an intraperitoneal injection of lidocaine, followed by a caesarean section to retrieve the embryos. …

Treatment of medulloblastoma using an oncolytic measles virus encoding the thyroidal sodium iodide symporter shows enhanced efficacy with radioiodine.

BackgroundMedulloblastoma is the most common malignant brain tumor of childhood. Although the clinical outcome for medulloblastoma patients has improved significantly, children afflicted with the disease frequently suffer from debilitating side effects related to the aggressive nature of currently available therapy. Alternative means for treating medulloblastoma are desperately needed. We have previously shown that oncolytic measles virus (MV) can selectively target and destroy medulloblastoma tumor cells in localized and disseminated models of the disease. MV-NIS, an oncolytic measles virus t

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… Animals were given an IP injection of 4.5 μg Xenolight Rediject D-Luciferin (Caliper Life Sciences) and kept under general anesthesia with isoflurane in O 2 delivered by a veterinary vaporizer. Images were obtained 20 minutes after luciferin administration. …

Pathogenic Role of FGFR3 Autoantibodies in Small Fiber Neuropathy.

Sensory neuronopathies (SNN) and small fiber neuropathies (SFN) are debilitating disorders associated with neuropathic pain, yet their underlying mechanisms remain poorly understood. Autoantibodies against fibroblast growth factor receptor 3 define a subset of patients with consistent reports of neuropathic pain harboring a distinct clinical phenotype characterized by small-fiber and non-length-dependent neuropathy, suggesting dorsal root ganglia (DRG) dysfunction. FGFR3-autoantibody-positive sera (FGFR3-AbS) bind to sensory neurons within dorsal root ganglia (DRG). The target of autoantibodie

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… Rats were anesthetized with 5% isoflurane for induction and maintained under 2.5% isoflurane. After confirming areflexia, a ≈2–3 cm incision was made on the right flank, approximately 1 cm lateral to the hip. …

Мелатонин за пределами хронобиологии: интеграция фармакокинетики, прогнозирование дозы и клинические данные.

Мелатонин установлен в качестве регулятора времени и сна в циркадиане, в то время как более широкий спектр зависящих от рецептора и независимых от рецептора биологических эффектов вызвал интерес к дополнительным видам терапевтического применения. В этом обзоре критически рассматривается вопрос о том, можно ли интерпретировать эти предлагаемые последствия в фармакологических рамках, основанных на воздействии. Мы интегрируем недавние доклинические и клинические данные с фармакокинетиками перорального и внутривенного мелатонина и с обычным дифференциальном уравнением (ОДВ) - прогнозом воздействия

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… . | Cardiac surgery/renal protection | PMID 36,586,514 [ 74 ] | Adults undergoing general anesthesia with intubation | Prospective double-blind randomized study; n = 50 | Oral melatonin 6 mg 2 h before surgery | Hemodynamic response, propofol/isoflurane/fentanyl requirements | Reduced MAP before/after … induction and reduced propofol and isoflurane requirements; did not fully attenuate intubation responses. | Anesthesia/premedication | PMID 38,269,180 [ 75 ] | Women undergoing induction of labor | Double-blind randomized placebo-controlled trial | Melatonin during induction of labor; route/dose not …

Antiseptic Functions of CGK012 against HMGB1-Mediated Septic Responses.

High mobility group box 1 (HMGB1), a protein with important functions, has been recognized as a potential therapeutic target for the treatment of sepsis. One possible mechanism for this is that inhibiting HMGB1 secretion can exert antiseptic effects, which can restore the integrity of the vascular barrier. (7S)-(+)-cyclopentyl carbamic acid 8,8-dimethyl-2-oxo-6,7-dihydro-2H,8H-pyrano[3,2-g]chromen-7-yl-ester (CGK012) is a newly synthesized pyranocoumarin compound that could function as a novel small-molecule inhibitor of the Wnt/β-catenin signaling pathway. However, no studies have yet determi

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… In Vivo Leukocyte Migration Assay Mice used in the in vivo experiment were anesthetized using a combination of 2% isoflurane in oxygen delivered through an inhaling chamber and a facemask attached to veterinary anesthesia equipment for small rodents. …

Oncofetal Chondroitin Sulfate Is a Highly Expressed Therapeutic Target in Non-Small Cell Lung Cancer.

Broad-spectrum therapeutics in non-small cell lung cancer (NSCLC) are in demand. Most human solid tumors express proteoglycans modified with distinct oncofetal chondroitin sulfate (CS) chains that can be detected and targeted with recombinant VAR2CSA (rVAR2) proteins and rVAR2-derived therapeutics. Here, we investigated expression and targetability of oncofetal CS expression in human NSCLC. High oncofetal CS expression is associated with shorter disease-free survival and poor overall survival of clinically annotated stage I and II NSCLC patients (n = 493). Oncofetal CS qualifies as an independ

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… Initially, 7-week-old female nude mice (ENVIGO, Indianapolis, IN, USA; Stock No. 069) were anesthetized with 3% isoflurane. Then, 100 μL of a cell suspension in PBS:Matrigel (Corning, Ref. …

Serial low doses of sorafenib enhance therapeutic efficacy of adoptive T cell therapy in a murine model by improving tumor microenvironment.

Requirements of large numbers of transferred T cells and various immunosuppressive factors and cells in the tumor microenvironment limit the applications of adoptive T cells therapy (ACT) in clinic. Accumulating evidences show that chemotherapeutic drugs could act as immune supportive instead of immunosuppressive agents when proper dosage is used, and combined with immunotherapy often results in better treatment outcomes than monotherapy. Controversial immunomodulation effects of sorafenib, a multi-kinases inhibitor, at high and low doses have been reported in several types of cancer. However,

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… The imaging studies were performed under 2% isoflurane was used for anesthesia during tumor inoculation and imaging acquisition. CO 2 was use for euthanasia the mice when isolated T cells or at the end of the experiment, and all efforts were made to minimize suffering. …

Proceedings 27th Symposium ESVN‐ECVN

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Обобщение и оценка 6-ариламинобензамидов в качестве позитронных фотографических лигандов для рецептора фингозина-1-фосфата-5.

Спингосин-1-фосфат-5 (S1P5) является одним из пяти мембранных белковых рецепторов G, которые активируются лизофосфолипидом, фосфатом-1, что приводит к регулированию многих клеточных процессов. Рецепторы S1P5 расположены на олигодендроцитах и предлагаются для оказания влияния на физиологию олигодендроцитов. Понимание модуляции S1P5 в ходе таких процессов, как ремиелионация, может иметь потенциальные возможности для демиелионизации расстройств CNS, таких, как множественный склероз (MS). В этой связи мы сообщаем об обобщении и предварительной оценке серии фторированных 6-ариламинобензамидов в кач

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… Anesthesia was induced with the use of an induction chamber with 3% isoflurane (Isoflo, APIECE) delivered in a mixture of 0.5 L min −1 of oxygen and 0.5 L min −1 nitrous oxide. … Once anesthesia was induced, the rat was transferred to the bed of the PET scanner (NanoPET/CT, Mediso Medical Imaging Systems, Budapest, Hungary) ensuring the nose was in the nose cone and anesthesia was maintained with 2–2.5% isoflurane (50/50 oxygen/nitrous oxide, 1 L min −1 ). …

Астроглиальная модуляция синаптической функции в недемилинированной коре головного мозга зависит от сигнала MyD88 в модели токсичного обезвоживания.

Прогрессивный неврологический спад в множественном склерозе связан с аксонной потерей и синаптической дисфункцией в недемилинированном нормальном сером веществе (NAGM) и занимает видное место в мозжечке. В отличие от ранних стадий заболеваний, когда синаптическая и нейро-аксональная патология коррелирует с масштабами инфильтрации клеток Т, для прогрессивных MS была предложена важная роль врожденной иммунной системы. Вместе с тем конкретный вклад микроглии и астроцитов в синаптическую патологию мозгового мозга в НГММ - независимо от адаптивной реакции Т клеток - по-прежнему в значительной степе

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… Preparation of acute cerebellar slices After 5 weeks, WT and MyD88 −/− animals were anesthetized with isoflurane and immediately decapitated. Preparation of acute cerebellar slices was carried out as described elsewhere [ 88 ]. …

Visfatin promotes multiple myeloma cell proliferation and inhibits apoptosis by inducing IL-6 production via NF-κB pathways.

BackgroundMultiple myeloma (MM) is the second most prevalent hematological malignancy that results in the proliferation of malignant plasma cells and the overproduction of monoclonal immunoglobulin. Visfatin plays an important role in the regulation of apoptosis, oxidative stress, and inflammation; however, to this date, the role of visfatin in multiple myeloma is unclear.ObjectiveTo explore the role of visfatin in multiple myeloma and find new targets for MM treatment.MethodsIn this study, expression of visfatin in bone marrow was detected by ELISA. The diagnostic value of visfatin was determ

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… The central disruption (cervical dislocation) method was used as the method of euthanasia under anesthesia with isoflurane. After that, the tumor tissue was collected. All the procedures used in these experiments were approved by the Ethics Committee of Lanzhou University Second Hospital. …

Расширенный полиглутамин в ATAXIN1 приводит к потере функции, которая усугубляет остроту множественного склероза в модели мыши EAE.

Ataxin-1 (ATXN1) — белок, в котором расширение его полиглутаминового тракта вызывает нервно-дегенеративное расстройство спинномозговой системы 1 (SCA1) в результате повышения функциональности. Недавно было продемонстрировано, что АТXN1 дикая порода играет защитную роль в регулировании жесткости экспериментального аутоиммунного энцефаломиелита (EAE) — хорошо зарекомендовавшей себя модели мыши для мультиклероза (MS). В этом исследовании дополнительно изучается роль ATXN1 с расширенным полиглутаминым трактом в контексте MS с использованием модели мыши EAE.МЕТОДЫ: Гемизигиозные мыши Atxn1 (Atxn12Q

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… EAE immunization Eight-week-old female mice were anesthetized using 1.8% isoflurane and injected subcutaneously in the flank/tail base with 200 mg of MOG 35 − 55 peptide (Genemed Synthesis Inc.) emulsified in complete Freund’s adjuvant (BD Biosciences) supplemented with 600 mg of Mycobacterium tuberculosis …

Validation of a data-driven multicomponent T2 analysis for quantifying myelin content in the cuprizone mouse model of multiple sclerosis.

BACKGROUND: Myelin quantification is essential for understanding a wide range of neurodegenerative pathologies. Voxel-wise multicomponent T2 (mcT2) analysis is the common approach for this purpose, yet no gold standard technique exist that can overcome the ambiguity of fitting several T2 components to a single-voxel signal. This challenge is further exacerbated in preclinical scan settings due to the addition of spurious diffusion encoding, resulting from the use of imaging gradients that are at least an order of magnitude larger than on typical clinical scanners. PURPOSE: Assess the utility

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… During MRI scans mice were anesthetized with isoflurane gas (1–2% in O 2 ), their body temperature maintained at 37°C using a water circulation system, and their breathing probed using an abdominal pressure pad. …

IL-6 and NFE2L2: A putative role for the hepatoprotective effect of N. Sativa, P. Ginseng and C. Sempervirens in AFB-1 induced hepatocellular carcinoma in rats.

In this study, we investigated possible hepato-protective effects of N. Sativa, P. Ginseng, and C. Sempervirens in Aflatoxin B1 (AFB-1) induced hepatocellular carcinoma rat model. Fifty-four male albino rats were randomly assigned to experimental groups. Alcoholic extracts of aforementioned herbs were administered orally for 28 days at different doses. IL-6, hs-CRP, MDA, SOD and NFE2L2 were determined using ELISA. Histopathological changes in treated groups were examined. Herbal treatment significantly reduced IL-6, hs-CRP, and MDA (P C. Sempervirens 600 and N. Sativa 1000 increased NFE2L2 lev

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… Neuroprotective effect of ginsenoside Rg1 prevents cognitive impairment induced by isoflurane anesthesia in aged rats via antioxidant, anti-inflammatory and anti-apoptotic effects mediated by the PI3K/AKT/GSK-3beta pathway. Mol Med Rep. 2016;14(3):2778–2784. doi: 10.3892/mmr.2016.5556. 57. Lu K.H. …

Morphine-3-glucuronide upregulates PD-L1 expression via TLR4 and promotes the immune escape of non-small cell lung cancer.

ObjectivePatients with cancer pain are highly dependent on morphine analgesia, but studies have shown a negative correlation between morphine demand and patient outcomes. The long-term use of morphine may result in abnormally elevated serum morphine-3-glucuronide (M3G) levels. Hence, the effects of M3G on tumor progression are worth studying.MethodsThe effects of M3G on PD-L1 expressions in human non-small cell lung cancer (NSCLC) cell lines were first evaluated. Activation of TLR4 downstream pathways after M3G treatment was then determined by Western blot. The effects of M3G on human cytotoxi

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… For mice tumor samples, mice were deeply anesthetized with isoflurane and perfused intracardially with PBS. LLC tumors were removed from the mice and post-fixed in 4% PFA overnight. …

The role and mechanisms of mesenchymal stem cells in postoperative cognitive dysfunction via immune network regulation.

Postoperative cognitive dysfunction (POCD) is a common neurological complication in elderly patients after surgery. Its pathophysiology is complex. Neuroinflammation, oxidative stress, and immune imbalance are all involved in this process. These changes can affect postoperative recovery and reduce patients' quality of life. As population aging continues to increase, the prevention and treatment of POCD have become important clinical issues. In recent years, mesenchymal stem cells (MSCs) have attracted attention in neurological diseases because of their immunomodulatory and tissue healing abili

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… Wang Z Meng S Cao L Critical role of NLRP3-caspase-1 pathway in age-dependent isoflurane-induced microglial inflammatory response and cognitive impairment [J] J Neuroinflammation 2018 15 1 109 10.1186/s12974-018-1137-1 29665808 PMC5904978 Wang Z, Meng S, Cao L, et al. … Critical role of NLRP3-caspase-1 pathway in age-dependent isoflurane-induced microglial inflammatory response and cognitive impairment [J]. J Neuroinflammation. 2018;15(1):109. 10.1186/s12974-018-1137-1 PMC5904978 29665808 59. …

Combined spatial metabolomics and 4D-DIA quantitative proteomics approaches to explore the relationship between lung cancer and the heart.

Lung cancer and cardiovascular disease pose persistent threats to human health, despite advancements in targeted therapy, percutaneous coronary intervention, and drug treatments. Challenges such as side effects, drug resistance, hospitalization rates, and mortality remain high. These diseases are closely linked, sharing common risk factors and intricately influencing each other. This study aims to investigate the interplay between lung disease and cardiovascular disease by examining changes in cardiac metabolites and protein expression using spatial metabolomics and 4D-DIA quantitative proteom

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… Spatial metabolomics experimental procedures Sample preparation After the final gavage, mice were anaesthetised with isoflurane and blood and hearts were taken. Frozen tissue samples were fixed in three drops of distilled water during the cutting stage. …

A Novel Intravesical Dextrose Injection Improves Lower Urinary Tract Symptoms on Interstitial Cystitis/Bladder Pain Syndrome.

Interstitial cystitis/bladder pain syndrome (IC/BPS) is a painful recurrent condition characterized by the discomfort of the bladder, and current treatment options have limited effectiveness. Prolotherapy is a well-known treatment that involves the injection of non-biologic solutions to reduce pain and/or promote proliferation of soft tissue, and dextrose is the most common injectate. This study investigated the effects of dextrose prolotherapy in a rat model of IC/BPS and patients with IC/BPS. We used cyclophosphamide to induce IC/BPS in rats, and intravesical instillation of 10% dextrose sol

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… Dextrose Prolotherapy in IC Rat Model Briefly, the rats were fasted for 12 h prior to bladder perfusion and anesthetized with isoflurane (Baxter, USA) by inhalation with a respirator. …