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Linoleate-pazopanib conjugation as active pharmacological ingredient to abolish hepatocellular carcinoma growth.

Small molecule compounds targeting multiple kinases involved in neoangiogenesis have shown survival benefits in patients with unresectable hepatocellular carcinoma (HCC). Nonetheless, despite the beneficial effects of multikinase inhibitors (MKIs), a lack of boosting adjuvant limits their objective response rate. Lipid conjugates have been used to improve delivery efficacy or pharmaceutical benefits for decades. However, the feasibility of utilizing lipid-drug conjugates (LDCs) in HCC regimens remains untested. In this study, oral feeding of linoleate-fluorescein isothiocyanate conjugates show

LncRNA Gas5, a Target of the Nonsense-Mediated Decay Pathway in the Brain, Regulates Neuroinflammation and Neurodegenerative Disease Pathways in a Tauopathy Mouse Model.

Dysregulation of target genes of nonsense-mediated decay (NMD) in the brain remains sparsely known in tauopathies. PS19 transgenic mice expressing human mutant P301S tau were evaluated for levels of lncRNA Gas5, a target of NMD. The results show Gas5 decreased in the brains of PS19 mice as they aged. We evaluated the consequences of blocking the NMD-mediated turnover of Gas5 using a small molecule administered intranasally to PS19 mice. The results show NPC86 disassociated Upf1 and Gas5, thereby hindering NMD. NPC86 treatment increased Gas5 levels in the cortex of male PS19 mice concurrent wit

Множественный склероз: то, что мы узнали и можем узнать из электронной микроскопии.

Множественный склероз (MS) — воспалительное нейродегенеративное заболевание, характеризующееся возникновением демиелинированных повреждений в центральной нервной системе. Повреждения MS могут подвергаться воспоминанию, временно смягчая симптомы, но по мере развития болезни воспроизводство становится менее эффективным. Помимо повреждений, нормальные появляющиеся ткани мозга имеют тонкие изменения, потенциально указывающие на более широкую диффузную патологию и/или повышенную подверженность воздействию повреждений. Патология MS варьируется между повреждениями серых и белых веществ и их нормальны

Премии победителей и резюме 32nd Ежегодный симпозиум Общества протеинов; Бостон, ОЭТ, июль 9-12, 2018.

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… Using fluorescence polarization assay, native electrophoresis, analytical gel filtration and analytical ultracentrifugation we show that doubly phosphorylated procaspase‐2 and 14‐3‐3 form an equimolar complex with a dissociation constant in the nanomolar range. …

Tuning epigenetics to enhance cancer virotherapy.

Cancer remains a major global health challenge, driving intensive research into novel therapeutic strategies. Oncolytic viruses (OVs) including herpesviruses, adenoviruses and echoviruses, have emerged as promising agents for cancer treatment, with several achieving regulatory approval. These viruses selectively lyse tumor cells and stimulate antitumor immunity. Nevertheless, their efficacy is constrained by limitations such as neutralization by serum factors and tumor cell resistance. Concurrently, epigenetic inhibitors modulate gene expression to suppress tumor proliferation and reshape immu

Генетическая основа болезни.

Генетика в той или иной степени играет определенную роль во всех заболеваниях. Изменения в нашей ДНК и различия в том, как эта ДНК функционирует (одиночка или комбинация), наряду с окружающей средой (которая включает образ жизни), способствуют болезнетворным процессам. В рамках этого обзора изучается генетическая основа человеческих заболеваний, включая однородные генетические расстройства, хромосомные диспропорции, эпигенетические, раковые и сложные расстройства, и рассматривается вопрос о том, каким образом наше понимание и технологические достижения могут быть использованы для обеспечения н

Paradoxical Left Ventricular Hypertrophy by Echocardiogram and Low Voltage ECG: A Key Clue in the Diagnostic Workup of Two Distinct Presentations of Cardiac AL Amyloidosis.

Cardiac amyloidosis remains a rare disease caused by the extracellular deposition of abnormal proteins-amyloids in the myocardium. These protein structures in the myocardium are associated with high morbidity and mortality, with prognosis hinging on early detection and treatment. Three main types of cardiac amyloidosis have been identified: light chain (AL), familial or senile (ATTR), and secondary amyloidosis which is associated with chronic inflammation. Cardiac amyloidosis classically presents as diastolic heart failure with symptoms of volume overload low voltage on electrocardiogram (ECG)

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

The effect of growth hormone on ovarian function recovery in a mouse model of ovarian insufficiency.

ObjectivesTo evaluate the effects and mechanisms of action of growth hormone (GH) in the recovery of ovarian function in ovarian insufficiency induced by cyclophosphamide (CP) in a mouse model.Materials and methodsAfter inducing ovarian insufficiency by administering 400 mg/kg of CP intraperitoneally to 6-week-old ICR mice, the mice were divided into four groups (control, CP, 1 mg/kg GH, and 2 mg/kg GH) with 10 mice in each group. GH was administered a week later for 7 days. Five mice from each group were sacrificed the next day, and their ovaries were collected for histological examination. T

Systemic administration of quality- and quantity-controlled PBMNCs reduces bisphosphonate-related osteonecrosis of jaw-like lesions in mice.

BACKGROUND: Definitive treatment strategies for bisphosphonate-related osteonecrosis of the jaw (BRONJ) have not been developed. Cell-based therapy is an attractive treatment method for intractable diseases in the medical and dental fields; however, approval has been challenging in dentistry. Recently, we developed quality- and quantity (QQ)-controlled peripheral blood mononuclear cells (PBMNCs) that have anti-inflammatory and pro-angiogenesis effects. The aim of this study was to investigate the effects of QQ-controlled PBMNC transplantation on BRONJ-like lesions in mice. METHODS: To create

The role of polyamine metabolism in remodeling immune responses and blocking therapy within the tumor immune microenvironment.

The study of metabolism provides important information for understanding the biological basis of cancer cells and the defects of cancer treatment. Disorders of polyamine metabolism is a common metabolic change in cancer. With the deepening of understanding of polyamine metabolism, including molecular functions and changes in cancer, polyamine metabolism as a new anti-cancer strategy has become the focus of attention. There are many kinds of polyamine biosynthesis inhibitors and transport inhibitors, but not many drugs have been put into clinical application. Recent evidence shows that polyamin

Совершенствование иммунотерапии клеток ИНКТ путем интеграции оптимизированных эндодоменов ЦАР и участников ИНКТ.

Клетки ИНКТ становятся весьма перспективной платформой иммунотерапии для лечения рака. Чтобы максимально увеличить антираковую активность CAR-INKT против рака крови, мы изучили оптимальные конструкции CAR и их комбинацию с новыми специфичными участниками INKT. Мы находим, что среди пяти различных эндодомен ЦАР, подкрепляемых возросшей вспыльчивостью и перекрестным разговором между Plexin D1 на CAR-INKT и Semaphorin 4 A на клетках миэломы, BCMA CD28z CAR-INKT проявляет наибольшую активность против миэломы. В частности, CD28z CAR-INKT опережает их коллег CAR-T. В целях расширения потенциала CAR-

Therapeutic Perspectives on the Modulation of G-Protein Coupled Estrogen Receptor, GPER, Function.

Estrogens exert their physiological and pathophysiological effects via cellular receptors, named ERα, ERβ, and G-protein coupled estrogen receptor (GPER). Estrogen-regulated physiology is tightly controlled by factors that regulate estrogen bioavailability and receptor sensitivity, while disruption of these control mechanisms can result in loss of reproductive function, cancer, cardiovascular and neurodegenerative disease, obesity, insulin resistance, endometriosis, and systemic lupus erythematosus. Restoration of estrogen physiology by modulating estrogen bioavailability or receptor activity

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… Specifically, CIMBA inhibits G-1 dependent calcium mobilization in HL60 cells (IC 50 = 75 nM), with a binding activity for ERα or ERβ <10 μM in fluorescence polarization assays. …

Epigenetic Activation of CCDC183-AS1 Promotes Osteoclastogenesis and Prostate Cancer Bone Metastasis Through the FUBP1/LIGHT Axis.

Bone metastasis (BM) is a major contributor to poor prognosis of prostate cancer (PCa); however, the underlying mechanisms of PCa BM remain poorly understood. A better understanding of these processes may provide critical insights for developing effective preventive and therapeutic strategies for PCa BM. In this study, significant upregulation of CCDC183-AS1 in PCa BM is identified, which is associated with disease progression. CCDC183-AS1 overexpression enhanced the ability of PCa cells to spread to the bone by inducing osteoclastogenesis and aiding in the creation of a BM niche. Mechanistica

Zebrafish Avatars towards Personalized Medicine-A Comparative Review between Avatar Models.

Cancer frequency and prevalence have been increasing in the past decades, with devastating impacts on patients and their families. Despite the great advances in targeted approaches, there is still a lack of methods to predict individual patient responses, and therefore treatments are tailored according to average response rates. "Omics" approaches are used for patient stratification and choice of therapeutic options towards a more precise medicine. These methods, however, do not consider all genetic and non-genetic dynamic interactions that occur upon drug treatment. Therefore, the need to dir

Искусственный интеллект основывается на достижениях в области наномедицины для лечения мозговых расстройств: обновленный обзор повествования.

Наномедицина - это наномасштабные, биосопоставимые материалы, которые предлагают перспективные альтернативы традиционным методам лечения расстройств мозга. Технологические достижения в области искусственного интеллекта (АИ), в частности машинного обучения (МЛ) и глубокого обучения (ДЛ), трансформируют область наномедицины путем совершенствования диагностики заболеваний, биомаркировки, прогнозирования и мониторинга заболеваний, целевых поставок наркотиков и терапевтического вмешательства, а также содействия расчетным и методологическим разработкам. Эти успехи могут быть достигнуты за счет анали

Clinical Efficacy and Potential Mechanisms of Acupoint Stimulation Combined With Chemotherapy in Combating Cancer: A Review and Prospects.

Although chemotherapy is the first-line treatment strategy for a variety of tumors, its side effects have limited its efficacy. This review summarizes the progress on the use of acupoint stimulation to combat chemotherapy-associated side effects, including chemotherapy-induced peripheral neuropathy (CIPN), cognitive impairment (CICI), and gastrointestinal toxicity (GI), as well as myelosuppression and immunosuppression. It was found that acupoint stimulation attenuated CIPN and GI by modulating the 5-hydroxytryptamine system in dorsal root ganglia, the dorsal horn of the spinal cord, and the d

Targeting strategies for bone diseases: signaling pathways and clinical studies.

Since the proposal of Paul Ehrlich's magic bullet concept over 100 years ago, tremendous advances have occurred in targeted therapy. From the initial selective antibody, antitoxin to targeted drug delivery that emerged in the past decades, more precise therapeutic efficacy is realized in specific pathological sites of clinical diseases. As a highly pyknotic mineralized tissue with lessened blood flow, bone is characterized by a complex remodeling and homeostatic regulation mechanism, which makes drug therapy for skeletal diseases more challenging than other tissues. Bone-targeted therapy has b

Техническое обслуживание дисмиелинических небольших диаметровых аксонов 14-3-3s в центральной нервной системе.

В центральной нервной системе миелин, образующийся вокруг нервных аксонов олигодендроцитом, позволяет эффективно проводить потенциалы действий и поддерживает аксонный гомеостаз. Таким образом, в случае демиелинизирующих заболеваний, таких, как множественный склероз (MS), наблюдается аксональное дегенерация и потеря, особенно в аксонах малых диаметров. Teneurin-4 Недостатки (недостатки)Ten-4 -) Мыши демонстрируют сильное дисмиэлирование микродиаметровых аксонов, но выживают больше года. Здесь мы хотели прояснить механизм выживания аксонов малого диаметра без миелина с помощью Ten-4 - Мыши. Имму

Immunoglobulin Light-Chain Amyloidosis: Clinical Presentations and Diagnostic Approach.

Systemic immunoglobulin light-chain (AL) amyloidosis is a rare disorder arising from a plasma cell clone that produces misfolded immunoglobulin light chains, which are deposited in various tissues and organs as amyloid fibrils. Signs and symptoms are typically vague and overlap with those arising from other common diseases; consequently, diagnosis of AL amyloidosis is challenging for clinicians. Substantial delays between onset of symptoms and diagnosis are common, and result in poorer outcomes, particularly in patients with cardiac AL amyloidosis and others who develop advanced organ dysfunct