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Регулирование Kynurenin Pathway в Relapping Rising Multial Sclerosis и его корреляции с прогрессивным нейродегенерацией.

Несмотря на отсутствие острых повреждений при многократном склерозе (MS), хроническое нейродегенерация продолжает развиваться, и потенциальным основополагающим механизмом может быть кинурайнский путь (КП). Как известно, продолжительная активация КП от хронического воспаления усугубляет прогресс нервно-дегенеративных заболеваний за счет производства нейротоксичных метаболитов. В числе 8 КП метаболиты, six из них, а именно: кинурень (КИН), 3- Гидроксилкилинин (3ГК), антраиличная кислота (АА), кинуриновая кислота (КИНА) и квинолинская кислота (QUIN) были связаны с нейродегенерацией.Чтобы получить

Nephrotoxicity in Bispecific Antibodies Recipients: Focus on T-Cell-Engaging Bispecific Antibodies.

Recently, bispecific antibodies (BsAbs) are evolving the landscape of cancer treatment and have significantly improved the outcomes of relapsed or refractory cancer patients. As increasing BsAbs entered clinical practice, specific toxicities have emerged, and renal side-effects have been described. However, there are a lack of studies analyzing the nephrotoxicity in the anti-cancer BsAbs recipients systematically. In this review, we demonstrate the etiologies, mechanisms, other risk factors and treatment options of kidney injury in the BsAbs recipients to provide a more comprehensive insight i

The CoV-2 outbreak: how hematologists could help to fight Covid-19.

COVID-19 is a medical emergency, with 20 % of patients presenting with severe clinical manifestations. From the pathogenetic point of view, COVID-19 mimics two other well-known diseases characterized by cytokine storm and hyper-activation of the immune response, with consequent organ damage: acute graft-versus-host disease (aGVHD) and macrophage activation syndrome (MAS). Hematologists are confident with these situations requiring a prompt therapeutic approach for switching off the uncontrolled cytokine release; here, we discuss pros and cons of drugs that are already employed in hematology in

Phase II trial of single-agent panobinostat consolidation improves responses after sub-optimal transplant outcomes in multiple myeloma.

Panobinostat is a pan-deacetylase inhibitor that modulates the expression of oncogenic and immune-mediating genes involved in tumour cell growth and survival. We evaluated panobinostat-induced post-transplant responses and identified correlative biomarkers in patients with multiple myeloma who had failed to achieve a complete response after autologous transplantation. Patients received panobinostat 45 mg administered three-times weekly (TIW) on alternate weeks of 28-day cycles commencing 8-12 weeks post-transplant. Twelve of 25 patients (48%) improved their depth of response after a median (ra

Tumor microenvironment signaling and therapeutics in cancer progression.

Tumor development and metastasis are facilitated by the complex interactions between cancer cells and their microenvironment, which comprises stromal cells and extracellular matrix (ECM) components, among other factors. Stromal cells can adopt new phenotypes to promote tumor cell invasion. A deep understanding of the signaling pathways involved in cell-to-cell and cell-to-ECM interactions is needed to design effective intervention strategies that might interrupt these interactions. In this review, we describe the tumor microenvironment (TME) components and associated therapeutics. We discuss t

Evaluation of salivary nitric oxide levels and anxiety in multiple sclerosis patients, with and without Xerostomia: correlation with clinical variables.

BACKGROUND: Xerostomia is a prevalent but often overlooked condition in multiple sclerosis (MS) patients, significantly impacting their quality of life and oral health. This cross-sectional observational study investigates the role of nitric oxide (NO) in the pathophysiology of multiple sclerosis (MS) and explores its association with xerostomia in MS patients. The primary objective was to compare salivary NO concentrations and stress levels between MS patients with and without xerostomia. METHODS: MS patients diagnosed by neurologists and MRI were categorized into two groups: those with xero

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… These medications were categorized into four groups: (1) Disease-modifying drugs (DMDs), including interferon beta-1a and interferon beta-1b; (2) Antidepressants; (3) The medications used for symptom management included anti-inflammatory drugs (corticosteroids); and (4) Drugs for managing relapses and …

Лизат парабасероид дистазонис предотвращает серьезные формы экспериментального аутоиммунного энцефаломиэлита, модифицируя примитивную реакцию клеток Т.

Микробиота кишечника влияет на реактивность иммунной системы, а парабактероид дистасонис появился как антивоспалительная комменза. Здесь мы изучили, может ли ли его лизат предотвратить сильные формы нейроинфламмации в экспериментальном аутоиммунном энцефаломиелите (EAE) у мышей и как эта превентивная стратегия влияет на кишечную микробиоту и иммунную реакцию. Лизат анаэробной культуры P. distasonis (Pd лизат) был в устной форме подан мышам C57BL/6 в четырех еженедельных дозах. Неделю спустя EAE был вызван, и через три недели после вводного курса была проведена оценка степени заболеваемости. Фе

The Role of Interleukin-1 in the Pathogenesis of Cancer and its Potential as a Therapeutic Target in Clinical Practice.

Interleukin-1 (IL-1) has long been known to be a key mediator of immunity and inflammation. Its dysregulation has been implicated in recent years in tumorigenesis and tumor progression, and its upregulation is thought to be associated with many tumors. Overexpression of the IL-1 agonists IL-1α and IL-1β has been shown to promote tumor invasiveness and metastasis by inducing the expression of angiogenic genes and growth factors. IL-1 blockers such as anakinra and canakinumab are already approved and widely used for the treatment of some autoimmune and autoinflammatory diseases and are currently

Recent advances in oncolytic virotherapy: insights from clinical trials and combination treatment strategies.

Background and aimOncolytic virotherapy is a novel therapeutic paradigm in oncology that uses viruses to selectively replicate within cancer cells, causing targeted tumor cell destruction with minimal toxicity to healthy tissues. With the rapid growth of oncolytic virotherapy and the accumulation of clinical studies on this subject, the present review aims to provide a comprehensive evaluation of current achievements in cancer treatments involving oncolytic viruses (OVs).Main textNumerous clinical trials have been conducted to assess the therapeutic efficacy and safety of OVs across a variety

33rd Annual Meeting & Pre-Conference Programs of the Society for Immunotherapy of Cancer (SITC 2018) : Washington, D.C., USA. 7-11 November 2018.

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Sildenafil, a Type-5 Phosphodiesterase Inhibitor, Fails to Reverse Myeloid-Derived Suppressor Cell-Mediated T Cell Suppression in Cells Isolated From Tuberculosis Patients.

Successful TB treatment is hampered by increasing resistance to the two most effective first-line anti-TB drugs, namely isoniazid and rifampicin, thus innovative therapies focused on host processes, termed host-directed therapies (HDTs), are promising novel approaches for increasing treatment efficacy without inducing drug resistance. We assessed the ability of Sildenafil, a type-5 phosphodiesterase inhibitor, as a repurposed compound, to serve as HDT target, by counteracting the suppressive effects of myeloid-derived suppressor cells (MDSC) obtained from active TB cases on T-cell responsivene

TGF-β in hematologic malignancies: molecular functions and clinical applications.

Transforming growth factor-β (TGF-β) represents a family of multifunctional cytokines, primarily secreted by megakaryocytes, monocytes, T lymphocytes, bone marrow stromal cells, and other cell types. TGF-β plays an essential role in various physiological processes, including the regulation of cell proliferation, differentiation, apoptosis, and immune homeostasis. As a key immunoregulatory cytokine, TGF-β contributes to an immunosuppressive network within the microenvironment of hematologic malignancies by modulating the functions of both adaptive and innate immune cells. Current studies have s

Drug Combinations as a First Line of Defense against Coronaviruses and Other Emerging Viruses.

The world was unprepared for coronavirus disease 2019 (COVID-19) and remains ill-equipped for future pandemics. While unprecedented strides have been made developing vaccines and treatments for COVID-19, there remains a need for highly effective and widely available regimens for ambulatory use for novel coronaviruses and other viral pathogens. We posit that a priority is to develop pan-family drug cocktails to enhance potency, limit toxicity, and avoid drug resistance. We urge cocktail development for all viruses with pandemic potential both in the short term (<1 to 2 years) and longer term wi

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… In another clinical trial ( 109 ), administration of two oral HIV protease inhibitors (lopinavir and ritonavir), an oral broad-spectrum viral replication inhibitor (ribavirin), and an injected anti-inflammatory (interferon beta-1b) reduced viral loads and improved symptoms in hospitalized patients compared … Triple combination of interferon beta-1b, lopinavir-ritonavir, and ribavirin in the treatment of patients admitted to hospital with COVID-19: an open-label, randomised, phase 2 trial. Lancet 395:1695–1704. doi: 10.1016/S0140-6736(20)31042-4. 110. …

Клиническое и экономическое воздействие работников, обеспечивающих уход за пациентами, страдающими множественным склерозом, в зависимости от состояния болезни.

Справочная информация: Исследования по вопросу о партнерах по уходу за пациентами с множественным склерозом (МС) являются ограниченными. Цели: Клиническое и экономическое воздействие на партнеров по уходу за работниками оценивалось с точки зрения степени заболеваемости MS. Методы: работники с супругами/домашними партнерами с НР из базы данных о партнерах по работе (Jan. 1, 2010- Декабрь. 31, 2019) имеют право на получение пособия, если: супруг/партнер имел по крайней мере 3 Связанная с НРICD-9-CM/ICD-10-CM::340xx/G35) заявления пациентов/акушеров/болезней в рамках 1 год (последняя претензия =

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… Disease modifying therapies considered for inclusion were subcutaneous interferon beta-1a, intramuscular interferon beta-1a, peginterferon beta-1a, subcutaneous interferon beta-1b, glatiramer acetate, daclizumab, teriflunomide, fingolimod, dimethyl fumarate, alemtuzumab, mitoxantrone, ocrelizumab, and …

Факторы, влияющие на развитие усталости у многочисленных склерозовых пациентов.

Усталость является одним из наиболее распространенных и недействующих симптомов у пациентов с MS, однако в настоящее время проводятся ограниченные исследования по изучению продольных детерминант развития усталости. Цель этого исследования состоит в том, чтобы выявить социально-демографические, поведенческие и клинические характеристики и терапевтические режимы, которые со временем соотносятся с усиливающейся усталостью у пациентов, у которых диагностированы синдромы MS. Это ретроспективная диаграмма 483 пациентов. Главным результатом этого стало изменение результатов по шкале 5 (MFIS-5) с перв

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… Low efficacy DMTs included interferon beta-1a, interferon beta-1b, and teriflunomide. Patients were receiving one DMT at a time, but may have used more than one DMT (from the same or different efficacy group) during the study interval due to failed response. …

Revisiting potential value of antitumor drugs in the treatment of COVID-19.

Since an outbreak started in China in 2019, coronavirus disease 2019 (COVID-19) has rapidly become a worldwide epidemic with high contagiousness and caused mass mortalities of infected cases around the world. Currently, available treatments for COVID-19, including supportive care, respiratory support and antiviral therapy, have shown limited efficacy. Thus, more effective therapeutic modalities are highly warranted. Drug repurposing, as an efficient strategy to explore a potential broader scope of the application of approved drugs beyond their original indications, accelerates the process of d

Neuroimaging and Neurocognitive Outcomes in Older Patients with Multiple Myeloma Treated with Chemotherapy and Autologous Stem Cell Transplantation.

There is a paucity of research on treatment-related neurotoxicity in older adults with multiple myeloma (MM) treated with high-dose chemotherapy (HDC) and autologous SCT (HDC/ASCT), despite the increasing use of this regimen. We examined resting state functional connectivity (RSFC), gray matter (GM) volume, neurocognitive function (NF), and proinflammatory cytokines (PCy) in older patients with MM pre- and post-HDC/ASCT. Eighteen patients underwent MRI, NF tests, and serum PCy measurements prior to HDC/ASCT, and fifteen patients completed a follow up five-months post-HDC/ASCT. There were signi

Exploiting the potential of the ubiquitin-proteasome system in overcoming tyrosine kinase inhibitor resistance in chronic myeloid leukemia.

The advent of tyrosine kinase inhibitors (TKI) targeting BCR-ABL has drastically changed the treatment approach of chronic myeloid leukemia (CML), greatly prolonged the life of CML patients, and improved their prognosis. However, TKI resistance is still a major problem with CML patients, reducing the efficacy of treatment and their quality of life. TKI resistance is mainly divided into BCR-ABL-dependent and BCR-ABL-independent resistance. Now, the main clinical strategy addressing TKI resistance is to switch to newly developed TKIs. However, data have shown that these new drugs may cause serio

Взаимосвязь между БМИ и когнитивом, инвалидностью и качеством жизненных показателей при множественном склерозе: вторичный анализ DISCOMS.

СВЯЗЬ МЕЖДУ индексом массы тела (ИОВ) и когнитивированием, инвалидностью и качеством жизни (QOL) является спорной при множественном склерозе (MS). Мы изучили связь между BMI и когнитивной функцией, инвалидностью и QoL в MS. МЕТОДЫ: Был проведен перекрестный вторичный анализ процесса ДИСКОМС для изучения связи между БМИ и когнитивом, инвалидностью и QoL. Когнитивная функция измерялась по методу проверки символических цифр (ССРМ), а инвалидность измерялась на основе расширенной шкалы показателей инвалидности (СЭДСС) и установленных пациентом ступеней инвалидности (ПДДС). Кольные маркеры измеряли

A Focus on CAR T-Cell Therapy and Bispecific Antibodies in Multiple Myeloma.

Significant strides have been made in the management of patients living with myeloma. However, patients with multiply relapsed or refractory multiple myeloma (MM) have a shorter overall survival; therefore, new treatments with novel mechanisms of action are needed in this patient population. Patients with relapsing disease require a full restaging workup, including whole body imaging to evaluate for extramedullary disease and lytic bone lesions, as well as bone marrow biopsy with fluorescence in situ hybridization to determine if the patient has any new chromosomal changes that are present. Th