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Биоразлагаемый электроспун PLGA Nanofibers-Encapsolated Trichinella Sphiralis Antigens защищает от повторного использования экспериментального аутоиммунного энцефаломилита и связанного с ним микробиота дисбиоз.

ЦЕЛЬ: " Тричинелла спиралис " создала сложные механизмы иммуномодуляции при посредничестве экскременто-секретарских продуктов (ESL1), которые позволяют ей выжить в принимающей стране. Следовательно, антигены ESL1 обладают прекрасным потенциалом для лечения аутоиммунных заболеваний, таких, как множественный склероз (MS). Однако вопрос о том, могут ли своевременные контролируемые поставки антигенов ESL1 в vivo, как и в случае естественных инфекций, повысить его терапевтический потенциал в отношении MS, до сих пор неизвестен.Для этого мы ввели антигены ESL1 в полихлорированные (лактидно

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… This analysis pointed to the extensive changes in microbial metabolism at the peak of the disease in control animals, marked by the enrichment of pathways involved in nucleotide, purine, and pyrimidine biosynthesis. … supplementation could prevent the polarization of astrocytes and microglia to neurotoxic phenotypes. 113 Ju et al 114 showed that the colonization of host microbiota with the genus Parasutterella strongly affects the faecal metabolome, increasing bile acid metabolites, succinate production, and purines …

Research Progress in Pharmacological Targeted Therapy for Myasthenia Gravis.

Myasthenia gravis (MG) is a disorder of neuromuscular junction transmission that is mediated by autoantibodies and depends on T cell help, causing fatigable muscle weakness. Limitations of conventional first-line treatments, including long-term adverse effects and inadequate control of refractory disease, have driven targeted therapy to the forefront of MG research. This narrative review summarizes second-line and later-line targeted biological and cellular therapies, covering agents directedat B and T cells, complement inhibitors, neonatal Fc receptor (FcRn) antagonists and cytokine inhibitor

Pathophysiology and Treatments of Complications of Waldenström's Macroglobulinemia.

Waldenstrom's macroglobulinemia (WM) or lymphoplasmacytic lymphoma is a B-cell malignancy characterized by lymphoplasmacytic cells in the bone marrow that secrete high amounts of immunoglobulin (Ig) M. The large pentameric structure of IgM leads to a variety of unique complications in WM, such as hyperviscosity syndrome, cryoglobulinemia and sensory neuropathy. Furthermore, malignant cells can infiltrate the central nervous system and lead to a variety of neurological complications, also known as Bing Neel Syndrome. Because of the unique pathophysiology of WM and these complications, their dia

Оценка прогнозируемых факторов, которые сокращают продолжительность лечения пациентов с множественной миеломой с использованием AI: Реальное продольное исследование в мире с использованием данных из базы данных о перспективах медицинских данных.

С учетом наличия новых методов лечения продолжительность терапии (DOT) сокращается с каждым увеличением линии лечения японских пациентов с множественной миеломой (MM). Цель этого исследования заключалась в выявлении факторов, которые сокращают DT у пациентов с MM с использованием процедуры машинного обучения (ML) из базы данных Medical Data Vision (MDV). 2003 в адрес 2022. Пациенты≥18 y) с недавно поставленным диагнозом MM, имеющим право на трансплантацию (продолжение первой линии терапии), или с рецидивом или рефракторным MM (продолжение второй или третьей строки терапии). Для выявления важны

Изучение воздействия программы ухода за больными на основе эффективности, интегрированной со стратегиями вмешательства в области питания, на результаты лечения нескольких больных миеломой с почечной неполноценностью.

ЦЕЛЬ: Изучение воздействия схемы ухода за больными на основе теории эффективности в сочетании с пищевым вмешательством на пациентов с множественной миеломой (ММ), связанной с почечной недостаточностью. МЕТОДЫ: Ninety-two Пациенты с MM были осложнены почечной недостаточностью в нашей больнице с апреля 2022 по апрель 2024 были произвольно разделены на контрольную группу (46 :: случаи с использованием традиционных медицинских сестер) и наблюдательной группы46 - случаи с использованием схемы ухода за больными, основанной на теории эффективности, в сочетании с мерами в области питания). Показатели

Изучение связи между 91 циркуляцией воспламенительных протеинов и нейродегенеративными заболеваниями: двухнаправленный анализ менделей и биоинформатики.

Циркуляция подстрекательских белков играет важную роль в патогенезе нейродегенеративных заболеваний (НДД). Однако точная причинно-следственная связь и механизмы, лежащие в основе их взаимодействия, по-прежнему остаются неясными. МЕТОДЫ: В каталоге GWAS были получены данные по 91 циркуляционному подстрекательскому протеину в рамках исследования ассоциации геномов (GWAS). Кроме того, данные GWAS о болезни Паркинсона (PD), болезни Альцгеймера (AD), амиотропическом боковом склерозе (ALS), множественном склерозе (MS) и ишемическом инсульте (IS) были получены в рамках проекта IEU Open GWAS. Для анал

Chemotherapy-induced acute kidney injury: epidemiology, pathophysiology, and therapeutic approaches.

Despite significant advancements in oncology, conventional chemotherapy remains the primary treatment for diverse malignancies. Acute kidney injury (AKI) stands out as one of the most prevalent and severe adverse effects associated with these cytotoxic agents. While platinum compounds are well-known for their nephrotoxic potential, other drugs including antimetabolites, alkylating agents, and antitumor antibiotics are also associated. The onset of AKI poses substantial risks, including heightened morbidity and mortality rates, prolonged hospital stays, treatment interruptions, and the need for

The Gut-Bone Marrow Axis: Deciphering the Mechanistic Impact of Microbial Metabolites on Hematopoietic Homeostasis and Disorders.

The gut microbiota is increasingly recognized as a dynamic endocrine-like microbial network that exerts systemic effects far beyond the gastrointestinal tract. Emerging evidence supports the existence of a "gut-bone marrow axis" through which gut-derived signals orchestrate hematopoietic homeostasis. However, shifting from correlative observations to causal mechanisms remains a major challenge in defining precise microbial impacts on hematopoietic outcomes. In this review, we systematically synthesize current knowledge on the molecular mechanisms by which microbial products-specifically short-

Therapeutic Potential of Chlorogenic Acid in Chemoresistance and Chemoprotection in Cancer Treatment.

Chemotherapeutic drugs are indispensable in cancer treatment, but their effectiveness is often lessened because of non-selective toxicity to healthy tissues, which triggers inflammatory pathways that are harmful to vital organs. In addition, tumors' resistance to drugs causes failures in treatment. Chlorogenic acid (5-caffeoylquinic acid, CGA), found in plants and vegetables, is promising in anticancer mechanisms. In vitro and animal studies have indicated that CGA can overcome resistance to conventional chemotherapeutics and alleviate chemotherapy-induced toxicity by scavenging free radicals

Current Approaches in the Treatment of Relapsed and Refractory Acute Myeloid Leukemia.

The limited sensitivity of the historical treatment response criteria for acute myeloid leukemia (AML) has resulted in a different paradigm for treatment compared with most other cancers presenting with widely disseminated disease. Initial cytotoxic induction chemotherapy is often able to reduce tumor burden to a level sufficient to meet the current criteria for "complete" remission. Nevertheless, most AML patients ultimately die from their disease, most commonly as clinically evident relapsed AML. Despite a variety of available salvage therapy options, prognosis in patients with relapsed or r

Combination therapy with novel agents for acute myeloid leukaemia: Insights into treatment of a heterogenous disease.

The treatment landscape of acute myeloid leukaemia (AML) is evolving rapidly. Venetoclax in combination with intensive chemotherapy or doublets or triplets with targeted or immune therapies is the focus of numerous ongoing trials. The development of mutation-targeted therapies has greatly enhanced the treatment armamentarium, with FLT3 inhibitors and isocitrate dehydrogenase inhibitors improving outcomes in frontline and relapsed/refractory (RR) AML, and menin inhibitors showing efficacy in RR NPM1mut and KMT2A-rearranged AML. With so many new drugs approved, the number of potential combinator

Small molecule metabolites: discovery of biomarkers and therapeutic targets.

Metabolic abnormalities lead to the dysfunction of metabolic pathways and metabolite accumulation or deficiency which is well-recognized hallmarks of diseases. Metabolite signatures that have close proximity to subject's phenotypic informative dimension, are useful for predicting diagnosis and prognosis of diseases as well as monitoring treatments. The lack of early biomarkers could lead to poor diagnosis and serious outcomes. Therefore, noninvasive diagnosis and monitoring methods with high specificity and selectivity are desperately needed. Small molecule metabolites-based metabolomics has b

Effect of N-Acetylcysteine on Cisplatin Toxicity: A Review of the Literature.

N-acetylcysteine (NAC) is a membrane-permeable cysteine precursor capable of enhancing the intracellular cysteine pool, enhancing cellular glutathione (GSH) synthesis, and thus potentiating the endogenous antioxidant mechanism. Late administration of NAC after cisplatin has been shown in different in vivo studies to reduce the side effects caused by various toxicities at different levels without affecting the antitumor efficacy of platinum, improving total and enzymatic antioxidant capacity and decreasing oxidative stress markers. These characteristics provide NAC with a rationale as a potenti

Metabolomics for hematologic malignancies: Advances and perspective.

With the use of advanced technology, metabolomics allows for a thorough examination of metabolites and other small molecules found in biological specimens, blood, and tissues. In recent years, metabolomics has been recognized that is closely related to the development of malignancies in the hematological system. Alterations in metabolomic pathways and networks are important in the pathogenesis of hematologic malignancies and can also provide a theoretical basis for early diagnosis, efficacy evaluation, accurate staging, and individualized targeted therapy. In this review, we summarize the prog

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… Glycine dehydrogenase has been found to promote GSH production, and knockdown of glycine dehydrogenase induced DNA damage, thereby inhibiting MM cell proliferation. [ 55 ] Previous publications have found that exogenous glycine only contributes to purine synthesis in melanoma. [ 56 ] In contrast, it … has been observed in a recent investigation that MM cells uptake exogenous glycine and further metabolize it into GSH, purines, and serines. [ 55 ] In summary, the increased presence of glycine within the BM contributes to the progression of MM by modulating the GSH equilibrium within MM cells. …

Management of mantle cell lymphoma in the elderly patient.

Mantle cell lymphoma is a relatively rare B-cell lymphoma with a specific genetic lesion and a typical immunophenotypic profile. The median age is 65 years. There is no curative treatment, except allogeneic stem cell transplantation for a selected group of patients. For the majority of patients, especially the elderly, the aim of therapy should therefore be a long progression-free survival. Age and comorbidity may hamper the use of the most active treatment regimen, such as high dose cytarabine and autologous stem cell transplantation. Therefore, it is a challenge to select the most appropriat

An adult patient with systemic mastocytosis and B-acute lymphoblastic leukemia.

Mastocytosis is a myeloproliferative neoplasm characterized by clonal expansion of abnormal mast cells, ranging from the cutaneous forms of the disease to mast cell leukemia. In a significant proportion of patients, systemic mastocytosis (SM) coexists with another hematologic malignancy, termed systemic mastocytosis with an associated hematologic nonmast cell lineage disorder (SM-AHNMD). Despite the pronounced predominance of concomitant myeloid neoplasms, the much more unusual coexistence of lymphoproliferative diseases has also been reported. Imatinib mesylate (IM) has a role in the treatmen

Coronavirus Disease (COVID-19) Control between Drug Repurposing and Vaccination: A Comprehensive Overview.

Respiratory viruses represent a major public health concern, as they are highly mutated, resulting in new strains emerging with high pathogenicity. Currently, the world is suffering from the newly evolving severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This virus is the cause of coronavirus disease 2019 (COVID-19), a mild-to-severe respiratory tract infection with frequent ability to give rise to fatal pneumonia in humans. The overwhelming outbreak of SARS-CoV-2 continues to unfold all over the world, urging scientists to put an end to this global pandemic through biological and

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… Favipiravir (FPV) Pyrazine carboxamide derivative selectively inhibits RNA-dependent RNA polymerase from RNA viruses by imitating purines or purine nucleosides during viral replication. … Purine analogs have also been shown to reduce favipiravir’s antiviral activity, implying that favipiravir-RTP and purine nucleosides compete for RdRp binding. …

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

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… Aside from lipid metabolism, both SARS-CoV-2 and tumor cells have a vigorous demand of purines and pyrimidines for nucleic acid synthesis, which acts as replication stress driving metabolic alterations of host cells or tumor cells [ 33 ]. … The results showed that folate and one-carbon metabolism of host cells were commandeered by SARS-CoV-2 to commit to de novo purine synthesis that was required for viral replication [ 33 ]. …

Post-Transplant Bendamustine as a Platform for Immune Modulation After Allogeneic Hematopoietic Cell Transplantation.

Post-transplant cyclophosphamide (PT-CY) remains the standard of care for graft-versus-host disease (GvHD) prophylaxis in haploidentical hematopoietic cell transplantation (HCT), yet relapse, delayed immune reconstitution, infections, and organ toxicity represent persistent and clinically meaningful limitations. Post-transplant bendamustine (PT-BEN) has been investigated as a biologically distinct alternative. In stringent haploidentical murine models, PT-BEN uncoupled GvHD from graft-versus-leukemia (GvL) effects through mechanisms centered on myeloid modulation and preservation of innate imm

Managing Tumor Lysis Syndrome in the Era of Novel Cancer Therapies.

Abstract Tumor lysis syndrome (TLS) is a potentially life-threatening emergency that can develop rapidly after the release of intracellular contents from lysed malignant cells. The advent of novel and targeted therapies that have improved tumor-killing efficacy has the potential to increase the risk of TLS when used as part of front-line therapy. A recent review of TLS risk in patients with hematologic malignancies treated with newer targeted agents highlighted the need to revisit TLS risk stratification and to describe the practical challenges of TLS prevention, treatment, and monitoring. Alt

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… Recently, febuxostat (Uloric), a non–purine selective inhibitor, was approved by the US Food and Drug Administration (FDA) for chronic management of hyperuricemia in patients with gout ( Takeda Pharmaceuticals U.S.A., Inc., 2013 ), is currently being studied in the TLS setting. … Allopurinol and febuxostat inhibit xanthine oxidase, the enzyme that converts hypoxanthine to xanthine and xanthine to uric acid ( Figure 2 ; Hu & Tomlinson, 2008 ; Pession, Melchionda, & Castellini, 2008 ), and thus prevent the formation of new uric acid from purines released by cancer cell lysis, reducing …