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RNA метилтрансферазы METTL8 устанавливает m3C32 в митохондриальном tRNASThr/Ser (UCN) для оптимизации структуры trNA и митохондриального перевода.

Модифицированные нуклеотиды в tRNA являются важными определяющими факторами сворачивания, структуры и функции. Здесь мы идентифицируем METTL8 как митохондриальный белок и активный РНК метилтрансферазы, ответственный за установку m3C32 в митохондриале человека (mt-)tRNAThr и mt-tRNAser (UCN). METTL8 имеет перекрестные связи с антикодоновой стволовой петлей (ASL) многих мт-тРНК в клетках, в связи с чем возникает вопрос о том, каким образом достигается целевая специфичность метилирования. Расчленение элементов распознавания mt-tRNA выявило наличие U34G35 и t6A37/(ms2)i6A37, которые одновременно п

Электрохимические датчики на основе полимера для диагностики нейродегенеративных заболеваний.

Острые и хронические нейродегенеративные заболевания (ND), включая множественный склероз (MS), болезнь Альцгеймера (AD) и болезнь Паркинсона (PD), характеризуются нейродегенерацией, которая представляет собой постепенный сбой и повреждение нейронов и аксонов в центральной нервной системе. Благодаря обнаружению соответствующих биомаркеров нейродегенеративных заболеваний (ND) стало возможным совершенствование клинических диагностических исследований, а также разработка и отслеживание успешных методов лечения заболеваний. Важные биомаркеры, такие, как белки тау, амилоид-β и α-синуклеины, имеют ва

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

"Something Good Has to Come Out of the Horror": A Qualitative Examination of Cancer Survivors' Attitudes Towards Participation in Research During the First Year of the COVID-19 Pandemic.

Introduction: The first year of the COVID-19 pandemic has been highly disruptive for people with cancer. Furthermore, it has been shown that accrual to cancer trials dropped substantially in 2020. Building on findings from a previous pilot survey, the present study used qualitative methods to gain insights into attitudes towards participation in research studies amongst people who have experienced cancer, in the context of the first year of the COVID-19 pandemic. Materials and Methods: We interviewed 13 participants from the UK, who were purposively sampled, including a broad sample of cancer

Radiographic Patterns and Clinical Correlates of Medication-Related Osteonecrosis of the Jaw (MRONJ): A Retrospective Analysis.

Objectives: This study aimed to evaluate the radiographic characteristics of medication-related osteonecrosis of the jaw (MRONJ) by digital panoramic radiographs and to investigate the associations between radiographic findings and clinical, demographic, and treatment-related variables in patients receiving antiresorptive therapy. Methods: A retrospective analysis was performed on 55 patients receiving antiresorptive therapy, categorized into a tooth-extraction group (n = 20) and an MRONJ group (n = 35). Standardized panoramic radiographs obtained at baseline (T0) and during the 6-month follow

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… Dentoalveolar surgical procedures are the most frequently reported precipitating factors in the development of MRONJ. Filleul et al. reported that tooth extraction constituted 67% of cases, followed by spontaneous onset (26%) and prosthesis- or torus-related trauma (7%) [ 11 ]. …

Short- and Long-Term Prognosis in Hemodynamically Stable Pulmonary Embolism With Unresectable or Metastatic Malignancies: The Role of Performance Status.

BackgroundThe simplified Pulmonary Embolism Severity Index (sPESI) has limitations when evaluating acute pulmonary embolism (PE) in patients with concurrent malignancy. Despite its utility in predicting outcomes among cancer patients, the role of the Eastern Cooperative Oncology Group Performance Status (ECOG PS) in acute PE remains underexplored. This study aims to assess the prognostic significance of ECOG PS ≥ 3 on short- and long-term mortality in acute PE with malignancy, correlating it with the sPESI.Methods and resultsWe retrospectively analyzed 44 hemodynamically stable acute PE patien

Systemic Sclerosis and Malignancy: A Review of Current Data.

Systemic sclerosis (SSc) is associated with increased risk of malignancy. The organ systems most commonly affected are the lungs, the breasts and the hematological system. Risk factors predisposing a SSc patient for development of malignancy are not well defined, and the pathogenic basis of the association is yet to be explained. The incidence of malignancies in SSc patients is variable from one report to another, but most importantly, questions regarding the role of immunosuppressive therapies and the effect of autoantibodies have weak or sometimes contradictory answers in most of the current

Neutralizing antibody against GDF15 for treatment of cancer-associated cachexia.

GDF15 (growth differentiation factor 15), also known as macrophage inhibitory cytokine 1 (MIC-1), is a circulating protein involved in the regulation of energy balance and weight control. Elevated levels of GDF15 have been associated with cachexia and reduced survival rates in cancer patients. Through the activation of the GFRAL (GDNF-family receptor α-like)-RET (Rearranged during Transfection) signaling pathway, GDF15 can induce weight loss, making it a potential target for treating cachexia. Currently, there are no approved antibody drugs specifically targeting GDF15 for cancer cachexia trea

EQUITY-MS: оценка качества исследования и лечения множественной скlerозы на основе данных пяти специализированных нейрологических центров в Великобритании — протокол исследования.

ВВЕДЕНИЕ: Социальные определяющие факторы здоровья — это условия, в которых живут люди, и системы вокруг них, которые формируют эти условия. Социальные определяющие факторы здоровья могут влиять на диагностику и лечение людей с множественной склерозом (МС), даже в странах с универсальной системой здравоохранения. Это исследование будет изучать, влияет ли возраст, пол и/или пол, проживание в более социально-экономически уязвимой зоне и принадлежность к миноритарной этнической группе на доступ к диагностике МС и лекарствам, модифицирующим течение болезни (ДМТ) для людей, проживающих в районах об

Hodgkin's Disease in Patients with HIV Infection.

Hodgkin lymphoma (HL) represents one of the most common non-AIDS-defining cancers with an increasing incidence overtime. Clinically, patients present advanced stages of disease with extranodal involvement in the majority of cases. In the last years, significant improvements in the treatment of patients with HL and HIV infection have been achieved. In the lack of randomized trials, several phase II studies have showed that in the era of highly active antiretroviral therapy (HAART) the same regimens employed in HIV-negative patients with HL can be used in HIV setting with similar results. Moreov

LncRNA CASC15 serves as a diagnostic biomarker for postmenopausal osteoporotic fractures and its knockdown enhances HBMSC osteogenic differentiation via miR-152-3p.

OBJECTIVE: Long non-coding RNA CASC15 plays a role in the development of various human diseases. However, the diagnostic role and molecular mechanisms of CASC15 in postmenopausal osteoporosis (PMOP) remain unclear. METHODS: This study enrolled 137 healthy postmenopausal women and 141 PMOP patients. CASC15 and miR-152-3p levels in serum and HBMSCs were measured via RT-qPCR. Western blotting and RT-qPCR were employed to analyze the protein and mRNA expression levels of osteogenic markers (RUNX2, ALP, OCN, Col I). CASC15's diagnostic value was assessed by the ROC curve. Proliferation (CCK-8) and

Cardiotoxicity Associated with Anti-CD19 Chimeric Antigen Receptor T-Cell (CAR-T) Therapy: Recognition, Risk Factors, and Management.

Chimeric antigen receptor T-cells (CAR-T) are improving outcomes in pediatric and adult patients with relapsed or refractory B-cell acute lymphoblastic leukemias and subtypes of non-Hodgkin Lymphoma. As this treatment is being increasingly utilized, a better understanding of the unique toxicities associated with this therapy is warranted. While there is growing knowledge on the diagnosis and treatment of cytokine release syndrome (CRS), relatively little is known about the associated cardiac events that occur with CRS that may result in prolonged length of hospital stay, admission to the inten

Osteonecrosis of the Jaws (ONJ) after Bisphosphonate Treatment in Patients with Multiple Myeloma: Decreasing ONJ Incidence after Adoption of Preventive Measures.

Bisphosphonates (BPs) are administered to Multiple Myeloma (MM) patients with bone lytic lesion. Osteonecrosis of the Jaw (ONJ) is a complication reported since 2003 in patients treated with intravenous (IV) BPs such as zoledronic acid and pamidronate, with 6%-26.3% frequency in early literature series, before some preventive measures were recommended. We evaluated the occurrence of ONJ with and without dental preventive measures in MM patients treated with BPs in our centre between 1996 and 2015. Since 2005, MM patients (already under treatment or before treatment) underwent a baseline mouth

Irish Endocrine Society 44th Annual Meeting.

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Synthesis and biological evaluation of a new polymeric conjugate and nanocarrier with osteotropic properties.

Bone-seeking (osteotropic) drug delivery systems (ODDS) represent an interesting solution for targeting different types of drugs to the bones. In particular, anticancer and antibacterial agents could take advantage of such therapeutic strategy. We have recently developed an innovative approach to this aim: a new osteotropic biomaterial was prepared, based on the conjugation of a poly(lactide-co-glycolide) (PLGA) with the bisphosphonate drug alendronate (PLGA-ALE); its hemo- and cytocompatibility were verified. Starting with this copolymer, an osteotropic nanoparticle system (NP) was produced f

Prognosis of concurrent renal impairment at diagnosis of multiple myeloma: a systematic review.

BackgroundMultiple myeloma is a malignant tumour of the blood in which abnormal proliferation of plasma cells leads to bone destruction, renal impairment, anaemia, and hypercalcaemia. Renal impairment caused by multiple myeloma is a common and serious condition; however, the prognosis of multiple myeloma at the time of diagnosis remains unclear.MethodWe conducted searches for literature in PubMed, Web of Science, Cochrane, Embase, CNKI, Wanfang, and VIP databases up to 30 April 2023. Progression-free survival and overall survival with and without renal impairment at the time of multiple myelom

Cataract Induced by Glucocorticoids.

Glucocorticoids (GCs) remain a cornerstone therapy for noninfectious uveitis and autoimmune disorders; however, chronic administration is strongly associated with sight-threatening complications, particularly glucocorticoid-induced cataracts (GIC). This comprehensive review synthesizes current evidence on the molecular pathogenesis, epidemiological patterns, and clinical management of GIC. Epidemiological analyses indicate that over 50% of patients receiving systemic corticosteroids for >60 days develop ocular complications, with cataract formation (36%) and glaucoma (16%) representing the pre

Вторичные аутоиммунные дерматологические расстройства, вызываемые агентами по биологическому иммунотерапии с множественным склерозом: систематический обзор сообщений о случаях.

ONTEXT: Множественный склероз (MS) является разрушительным аутоиммунным нейродегенеративным заболеванием, в связи с которым лекарственные средства для лечения заболеваний (DMD) ассоциируются с вторичными аутоиммунными дерматологическими расстройствами. ЦЕЛИ: Данный систематический обзор докладов по конкретным делам направлен на изучение документально подтвержденных сообщений о случаях применения биологических препаратов при борьбе с нападениями с применением НР и распространением заболеваний, которые коррелируют с такими дерматологическими осложнениями. ИСТОЧНИКИ: Был проведен систематический

The trinity of T cell engagement: navigating the molecular and clinical landscape of CAR-T, TILs, and TCEs in the war against cancer.

The advent of cancer immunotherapy has fundamentally restructured the oncological paradigm, moving away from agents that directly target tumor cell kinetics toward strategies that empower the host immune system to recognize and eliminate malignancy. Central to this revolution is the cytotoxic T lymphocyte (CTL), now harnessed as a potent "living drug" through engineered and naturally selected modalities. This review provides a critical, in-depth examination of the three dominant pillars of T cell-driven therapies: Chimeric Antigen Receptor T-cell (CAR-T) therapy, Tumor-Infiltrating Lymphocyte

Real-world prognostic factors in autotransplanted multiple myeloma patients with severe renal impairment: study of the Polish Myeloma Study Group.

INTRODUCTION: The prognostic factors in autotransplanted multiple myeloma (MM) patients with concomitant advanced chronic kidney disease (CKD) are poorly understood, limited, and controversial. MATERIAL AND METHODS: We retrospectively analysed 44 patients with MM and CKD (eGFR < 40 ml/min), present both at diagnosis and at autologous stem cell transplantation (ASCT), with no improvement of renal function in-between. RESULTS: Patients exhibiting deeper paraprotein responses to pre-transplant treatment predicted better response post ASCT (odds ratio (OR) = 11.6, p = 0.028) and longer progressi