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Quantification of promoting efficiency and reducing toxicity of Traditional Chinese Medicine: A case study of the combination of Tripterygium wilfordii hook. f. and Lysimachia christinae hance in the treatment of lung cancer.

Traditional Chinese medicine (TCM) usually acts in the form of compound prescriptions in the treatment of complex diseases. The herbs contained in each prescription have the dual nature of efficiency and toxicity due to their complex chemical component, and the principle of prescription is usually to increase efficiency and reduce toxicity. At present, the studies on prescriptions have mainly focused on the consideration of the material basis and possible mechanism of the action mode, but the quantitative research on the compatibility rule of increasing efficiency and reducing toxicity is stil

ASENT 2022 Annual Meeting.

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… Gammaitoni, Zogenix, Inc., Emeryville, CA, USA Abstract Fenfluramine’s dual activity at serotonergic and Sigma-1 receptors has positive effects on memory, learning, and cognition. …

Rediscovering trazodone for the treatment of major depressive disorder.

Trazodone is a triazolopyridine derivative that belongs to the class of serotonin receptor antagonists and reuptake inhibitors (SARIs). The drug is approved and marketed in several countries worldwide for the treatment of major depressive disorder (MDD) in adult patients. In clinical studies, trazodone has demonstrated comparable antidepressant activity to other drug classes, including tricyclic antidepressants (TCAs), selective serotonin reuptake inhibitors (SSRIs) and serotonin-noradrenaline (norepinephrine) reuptake inhibitors (SNRIs). Moreover, the SARI action of trazodone may overcome the

Иммунный транскриптомный профиль у взрослых женских свиней: доминантный статус оказывает большее влияние, чем экологическая обогащение.

ОКРУЖАЮЩАЯ СРЕДА: Оценка благосостояния сельскохозяйственных животных имеет решающее значение, однако по-прежнему отсутствуют практические физиологические средства. В этом исследовании мы проверили, обнаруживает ли периферийный транскриптом моноядерной клетки крови (PBMC) вариации в связи с благосостоянием свиней. Для этого мы сравнивали животных, состояние благосостояния которых было расценено как отличающееся из-за их жизни в более или менее обогащенной среде и из-за их различного доминирующего положения. Совы размещались в обычном помещении (C, n = 36) или обогащенного (E, n = 35) среда с д

Proteasome inhibition protects blood-brain barrier P-glycoprotein and lowers Aβ brain levels in an Alzheimer's disease model.

BackgroundLoss of P-glycoprotein (P-gp) at the blood-brain barrier contributes to amyloid-β (Aβ) brain accumulation in Alzheimer's disease (AD). Using transgenic human amyloid precursor protein (hAPP)-overexpressing mice (Tg2576), we previously showed that Aβ triggers P-gp loss by activating the ubiquitin-proteasome pathway, which leads to P-gp degradation. Furthermore, we showed that inhibiting the ubiquitin-activating enzyme (E1) prevents P-gp loss and lowers Aβ accumulation in the brain of hAPP mice. Based on these data, we hypothesized that repurposing the FDA-approved proteasome inhibitor

UFMTrack, "Недоходный миграционный трекер", позволяющий проанализировать весь многоэтапный каскад экстравазии иммунных клеток через барьер кровеносного мозга в микрофлюидовых устройствах.

Эндотелиальный барьер кровеносного мозга (БДБ) строго контролирует оборот иммунных клеток в центральную нервную систему (КНС). В таких нейро-воспалительных заболеваниях, как множественный склероз, этот жесткий контроль, однако, нарушается, что приводит к инфильтрации иммунных клеток в CNS. Разработка моделей BBB in vitro в сочетании с микрофлюидовыми устройствами способствовала более глубокому пониманию клеточных и молекулярных механизмов посредничества многоэтапной экстравазии Т-клеток по всему BBB. Одним из основных узких мест в этих исследованиях in vitro является отсутствие надежного и авт

Drug Repurposing for the Management of Depression: Where Do We Stand Currently?

A slow rate of new drug discovery and higher costs of new drug development attracted the attention of scientists and physicians for the repurposing and repositioning of old medications. Experimental studies and off-label use of drugs have helped drive data for further studies of approving these medications. A deeper understanding of the pathogenesis of depression encourages novel discoveries through drug repurposing and drug repositioning to treat depression. In addition to reducing neurotransmitters like epinephrine and serotonin, other mechanisms such as inflammation, insufficient blood supp

Inhibition of Cxcr4 chemokine receptor signaling improves habituation learning in a zebrafish model of neurofibromatosis.

Neurofibromatosis type 1 (NF1) is a neurogenetic disorder caused by loss-of-function mutations in the gene neurofibromin 1 (NF1). NF1 encodes neurofibromin, a multifunctional tumor-suppressing protein that regulates Ras, cAMP and dopamine signaling. NF1 predisposes patients to a wide range of symptoms, including peripheral nerve tumors, brain tumors and cognitive dysfunction. Despite considerable work using animal models to investigate the role of neurofibromin in behavior, translating research into treatment for NF1-associated cognitive dysfunction has not yet been successful. Here, we provid

Therapeutic potential of alpha-tocopherol in reducing oxidative stress and inflammatory damage after experimental traumatic brain injury and pentylenetetrazol-induced seizures.

The effects of alpha-tocopherol on seizure parameters, locomotor-cognitive functions, inflammatory response, oxidative stress response, histopathological changes, immunohistochemical parameters, and miRNA fold changes were investigated in rats with traumatic brain injury (TBI) and pentylenetetrazol (PTZ)-induced seizures. Sprague-Dawley male rats were randomly divided into three groups: Control (n = 8), TBI + PTZ (n = 10), and TBI + PTZ + tocopherol (n = 10). After inducing TBI in animals using the weight-drop method, increased post-injury seizure susceptibility was achieved by administering s

Glutathione Transferase P1-1 an Enzyme Useful in Biomedicine and as Biomarker in Clinical Practice and in Environmental Pollution.

Glutathione transferase P1-1 (GSTP1-1) is expressed in some human tissues and is abundant in mammalian erythrocytes (here termed e-GST). This enzyme is able to detoxify the cell from endogenous and exogenous toxic compounds by using glutathione (GSH) or by acting as a ligandin. This review collects studies that propose GSTP1-1 as a useful biomarker in different fields of application. The most relevant studies are focused on GSTP1-1 as a biosensor to detect blood toxicity in patients affected by kidney diseases. In fact, this detoxifying enzyme is over-expressed in erythrocytes when unusual amo

Analgesic Alkaloids Derived From Traditional Chinese Medicine in Pain Management.

Chronic pain is one of the most prevalent health problems. The establishment of chronic pain is complex. Current medication for chronic pain mainly dependent on anticonvulsants, tricyclic antidepressants and opioidergic drugs. However, they have limited therapeutic efficacy, and some even with severe side effects. We turned our interest into alkaloids separated from traditional Chinese medicine (TCM), that usually act on multiple drug targets. In this article, we introduced the best-studied analgesic alkaloids derived from TCM, including tetrahydropalmatine, aloperine, oxysophocarpine, matrine

Danshenol B alleviates central post-stroke pain by regulating the PIK3CG/NLRP3 signaling pathway.

BACKGROUND: Central post-stroke pain (CPSP) is a debilitating neuropathic condition that significantly impairs quality of life and is challenging to manage. Salvia miltiorrhiza (Danshen), a traditional Chinese herb, has demonstrated efficacy against neuropathic pain, but its active analgesic components and underlying mechanisms remain unclear. This study investigated the therapeutic potential of Danshenol B, an active component of Danshen, in a CPSP mouse model, focusing on its mechanism of action via the phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma isoform (PIK3CG)/N

Short-Chain Fatty Acid Production by Gut Microbiota Predicts Treatment Response in Multiple Myeloma.

PurposeThe gut microbiota plays important roles in health and disease. We questioned whether the gut microbiota and related metabolites are altered in monoclonal gammopathies and evaluated their potential role in multiple myeloma and its response to treatment.Experimental designWe used 16S rRNA sequencing to characterize and compare the gut microbiota of patients with monoclonal gammopathy of undetermined significance (n = 11), smoldering multiple myeloma (n = 9), newly diagnosed multiple myeloma (n = 11), relapsed/refractory multiple myeloma (n = 6), or with complete remission (n = 9). Short-

Обоснование и проектирование многоцентрового, национального, случайного, открытого испытания на этапе III: аллогенная трансплантация стволовых клеток как потенциальное лечение пациентов с повторной или прогрессирующей множественной миеломой (AlloRelapseM Study).

СПРАВОЧНАЯ ИНФОРМАЦИЯ: Несмотря на значительные улучшения в лечении миеломы, большинство пациентов, в конечном счете, вновь вернулись к нормальной жизни или добились прогресса. Пациенты с множественной миеломой, которые вновь вернулись после начальной высокодозированной химиотерапии с аутологическими стволовыми клетками, имеют средний прогресс свободного выживания вплоть до 2-3 годы в зависимости от факторов риска, таких, как продолжительность предыдущей ремиссии. В последние годы появляется все больше данных, свидетельствующих о том, что пересадка стволовых клеток может стать перспективным ва

Amiloride ameliorates muscle wasting in cancer cachexia through inhibiting tumor-derived exosome release.

BACKGROUND: Cancer cachexia (CAC) reduces patient survival and quality of life. Developments of efficient therapeutic strategies are required for the CAC treatments. This long-term process could be shortened by the drug-repositioning approach which exploits old drugs approved for non-cachexia disease. Amiloride, a diuretic drug, is clinically used for treatments of hypertension and edema due to heart failure. Here, we explored the effects of the amiloride treatment for ameliorating muscle wasting in murine models of cancer cachexia. METHODS: The CT26 and LLC tumor cells were subcutaneously in

Eukaryotic initiation factors: central factor associating mRNA translational plasticity during neuropathic pain progression.

Neuropathic pain causes plasticity in the nervous system, which is often associated with altered protein synthesis. Proteins are the key executors of cellular functions, and their alteration is closely related to the occurrence of neuropathic pain. Protein synthesis is a finely regulated process involving the interaction of multiple biomolecules. Among them, the eukaryotic translation initiation factors (eIFs) are a group of key regulatory proteins that control the initiation phase of protein translation and thus influence the rate and type of protein synthesis. Recent studies have shown that

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… Genomic action of Sigma-1 receptor chaperone relates to neuropathic pain . Mol Neurobiol . ( 2021 ) 58 : 2523 – 41 . doi: 10.1007/s12035-020-02276-8 , PMID: 33459966 PMC8128747 83. Raught B Gingras AC . eIF4E activity is regulated at multiple levels . …

Оптимальный выбор способа управления лекарствами в отношении внутримышечной и подкожной инъекции.

Внутримышечное (IV), внутримышечное (IM) и подкожное (SC) three - наиболее часто используемые пути инъекции для лечения лекарств. Время от времени проводились сравнительные исследования СК по отношению к IV, IM по отношению к IV, или IM по сравнению с СК, и некоторые новые выводы совершенно отличаются от рекомендаций в отношении дозировки, описанных в предписаниях в отношении информации. Однако врачи, возможно, до сих пор не знают о таких новых фактах при выборе методов лечения. Поиск литературы MetodsA был проведен с использованием PubMed, MedLINE и Web of Sciences TM Core Collection для анал

The Inclusion of Dietary and Medicinal Mushrooms into Translational Oncology: Pros and Cons at the Molecular Level.

Mushrooms are valued for their nutritional qualities and have been used in traditional medicine since the Neolithic era. They exhibit various bioactivities, including antioxidant, hypocholesterolemic, immunomodulatory, and anticancer effects. The anticancer effects arise via direct action on tumor cells and indirect modulation of the immune system; the latter is the predominant mechanism. Numerous studies indicate that various mushroom species are potent immunostimulants because their cell wall polysaccharides and proteoglycans are recognized by intestinal immune cells. This enhances antitumor

Crosstalk between glucocorticoid and mineralocorticoid receptors boosts glucocorticoid-induced killing of multiple myeloma cells.

The glucocorticoid receptor (GR) is a crucial drug target in multiple myeloma as its activation with glucocorticoids effectively triggers myeloma cell death. However, as high-dose glucocorticoids are also associated with deleterious side effects, novel approaches are urgently needed to improve GR action in myeloma. Here, we reveal a functional crosstalk between GR and the mineralocorticoid receptor (MR) that plays a role in improved myeloma cell killing. We show that the GR agonist dexamethasone (Dex) downregulates MR levels in a GR-dependent way in myeloma cells. Co-treatment of Dex with the

Mielopoiesis временно динамичен и регулируется образом жизни, чтобы изменить множественный склероз.

Моноциты и нейтрофилы из миэлоидной линии способствуют множеству склероза (MS), но динамика миэлопоисиса во время MS неясна. Здесь мы обнаружим связь между стилем жизни, миэлопоисисом и нейроинфламмацией. В мышах с аутоиммунным энцефаломиэлитом (RR-EAE) миэлопоисис в бедренной части, позвоночнике и селезенке поднимается до возникновения болезни и во время ремиссии, перед пиками клинической инвалидности и нейро-воспаления. В прогрессивном EAE (P-EAE) позвоночник mielopoiesis устойчиво поднимается во всех болезнях, в то время как бедра и селезенка mielopoies поднимаются до того, как они упадут п