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Transcriptome Analysis Reveals Altered Inflammatory Pathway in an Inducible Glial Cell Model of Myotonic Dystrophy Type 1.

Myotonic dystrophy type 1 (DM1), the most frequent inherited muscular dystrophy in adults, is caused by the CTG repeat expansion in the 3'UTR of the DMPK gene. Mutant DMPK RNA accumulates in nuclear foci altering diverse cellular functions including alternative splicing regulation. DM1 is a multisystemic condition, with debilitating central nervous system alterations. Although a defective neuroglia communication has been described as a contributor of the brain pathology in DM1, the specific cellular and molecular events potentially affected in glia cells have not been totally recognized. Thus,

Neutrophil diversity and function in health and disease.

Neutrophils, the most abundant type of granulocyte, are widely recognized as one of the pivotal contributors to the acute inflammatory response. Initially, neutrophils were considered the mobile infantry of the innate immune system, tasked with the immediate response to invading pathogens. However, recent studies have demonstrated that neutrophils are versatile cells, capable of regulating various biological processes and impacting both human health and disease. Cytokines and other active mediators regulate the functional activity of neutrophils by activating multiple receptors on these cells,

Leveraging the bacteria for enhanced cancer immunotherapy: from a perspective of synthetic biology.

In recent years, synthetic biology has been widely applied to engineer and program cellular behaviors. Using this approach, bacteria can be designed to express immunotherapeutic agents, improve tumor targeting, and deliver therapeutic payloads directly to tumor sites. To further improve efficacy, strategies such as hypoxia-responsive promoters, bacterial swarming, and extracellular vesicles (EVs) have been investigated, along with the synergistic effects of combining bacterial therapy with other treatments (e.g., photodynamic therapy, chemotherapy, immune checkpoint inhibitors). This review su

Role of myeloid-derived suppressor cells in tumor recurrence.

The establishment of primary tumor cells in distant organs, termed metastasis, is the principal cause of cancer mortality and is a crucial therapeutic target in oncology. Thus, it is critical to establish a better understanding of metastatic progression for the future development of improved therapeutic approaches. Indeed, such development requires insight into the timing of tumor cell dissemination and seeding of distant organs resulting in occult lesions. Following dissemination of tumor cells from the primary tumor, they can reside in niches in distant organs for years or decades, following

Оптимизация результатов цилтакабтагенской автолейкеля: реальный опыт и передовая практика одного учебного центра.

Ciltacabtagen autoleucel (cilta-cel), антигенная зрелость B-клеток (BCMA), направленная на химерик антиген-рецептор Т-клектор (CAR-T), изменила методы лечения повторной или рефрактной множественной миеломы и продемонстрировала долговременную, бестерапную ремиссию у пациентов (CAR-T).CARTITUDE-1:: медианный показатель общего выживания, 60.7 месяцев и 33% Число пациентов, выживавших без прогрессирования ≥5 США). Хотя ключевые клинические испытания продемонстрировали беспрецедентную глубину и долговечность реакции, население реального мира иногда может отличаться от когорт, пригодных для проведен

Management of infection and ocular complications in pediatric SJS/TEN-like acute graft-versus-host disease: a clinical case study and literature review.

Acute graft-versus-host disease (aGVHD) with skin manifestations reminiscent of Stevens-Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN) is associated with poor outcomes. However, optimal management strategies to enhance quality of life in SJS/TEN-like aGVHD remain undefined. This study aims to investigate the management of complex infections and acute ocular injury in patients with SJS/TEN-like aGVHD following allogeneic hematopoietic stem cell transplantation. We conducted a comprehensive analysis of the treatment course for a patient with SJS/TEN-like aGVHD, complemented by a lit

Декодирование GPCR, сигнализирующее перепрограммирование рака: молекулярные механизмы и терапевтические последствия.

G белковые рецепторы (GPCR) представляют собой крупнейшую мембранную группу рецепторов в геноме человека и служат ключевыми регуляторами клеточного сигнала, гомеостаза и фармакологической реакции. Помимо их классической роли в посредничестве внеклеточной стимуляции по зависящим от G-протеина и независимым путям, которые играют ключевую роль при помощи GPCR сигнальных путей, включая CAMP-PKA/EPAC, IP3/PLC, PI3K/Akt/mTOR и ERK/MAPK cascades, в вождении онкогенного распространения, апоптоза и метастаза. Кроме того, ГПХР замешаны в опухоли с помощью различных молекулярных механизмов, в рамках кото

Parasites revive hope for cancer therapy.

Parasites have attained a life-long stigma of being detrimental organisms with deleterious outcomes. Yet, recently, a creditable twist was verified that can dramatically change our perception of those parasites from being a source of misery to millions of people to a useful anti-cancerous tool. Various parasites have shown promise to combat cancer in different experimental models, including colorectal, lung, and breast cancers, among others. Helminths and protozoan parasites, as well as their derivatives such as Echinococcus granulosus protein KI-1, Toxoplasma gondii GRA15II, and Trypanosoma c

The Role of Cullin-RING Ligases in Striated Muscle Development, Function, and Disease.

The well-orchestrated turnover of proteins in cross-striated muscles is one of the fundamental processes required for muscle cell function and survival. Dysfunction of the intricate protein degradation machinery is often associated with development of cardiac and skeletal muscle myopathies. Most muscle proteins are degraded by the ubiquitin-proteasome system (UPS). The UPS involves a number of enzymes, including E3-ligases, which tightly control which protein substrates are marked for degradation by the proteasome. Recent data reveal that E3-ligases of the cullin family play more diverse and c

Donor's age influences outcome in haploidentical hematopoietic stem cell transplantation with post-transplant cyclophosphamide - a single center experience.

Haploidentical stem cell transplantation (haplo-SCT) using post-transplantation cyclophosphamide (post-Cy) is considered a reasonable therapeutic option for patients who lack matched donor or who urgently need transplant procedure due to high risk disease. We analyzed the results of haplo-SCT performed in years 2018-2023. Eighty one patients (46 males) at median age of 52 years underwent haplo-SCT using peripheral blood as a stem cell source in most cases. Indications included hematological malignancies (acute leukemias in 88% of cases). In 25 cases (31%) transplantation was performed in relap

Evaluating natalizumab first-line and later-line use in multiple sclerosis: a US claims database analysis.

BACKGROUND: Limited information exists on the healthcare resource utilization (HCRU) associated with real-world natalizumab used as a first-line (1L) versus later-line (2L+) treatment in multiple sclerosis (MS). OBJECTIVES: To describe natalizumab use in newly diagnosed MS patients treated as 1L or 2L+ and evaluate unadjusted annualized relapse rates (ARR) and MS-related HCRU before and after treatment initiation. DESIGN: This retrospective observational study utilized Komodo Health Sentinel claims data from October 2015 to August 2022. The study included adults diagnosed with incident MS wh

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… When natalizumab was reintroduced into the US market in 2006, it was generally recommended as a second-line therapy in the US label due to the associated risk of progressive multifocal leukoencephalopathy (PML), a rare yet serious brain infection caused by mutated pathogenic forms of the JC virus. …

The Glucocorticoid Receptor: Isoforms, Functions, and Contribution to Glucocorticoid Sensitivity.

Glucocorticoids exert pleiotropic effects on all tissues to regulate cellular and metabolic homeostasis. Synthetic forms are used therapeutically in a wide range of conditions for their anti-inflammatory benefits, at the cost of dose and duration-dependent side effects. Significant variability occurs between tissues, disease states, and individuals with regard to both the beneficial and deleterious effects. The glucocorticoid receptor (GR) is the site of action for these hormones and a vast body of work has been conducted understanding its function. Traditionally, it was thought that the anti-

Overcoming temozolomide resistance in glioma: recent advances and mechanistic insights.

Temozolomide (TMZ) remains the cornerstone chemotherapy for glioma, yet intrinsic and acquired resistance mechanisms significantly limit its clinical effectiveness. This review summarizes the multifaceted molecular pathways contributing to TMZ resistance, including enhanced DNA repair mechanisms such as O6-methylguanine-DNA methyltransferase (MGMT), mismatch repair (MMR), and base excision repair (BER). Additional resistance factors include genetic mutations that affect the drug response, dysregulated non-coding RNAs (miRNAs, lncRNAs, and circRNAs), glioma stem cells (GSCs), cytoprotective aut

Генетическое или терапевтическое нарушение траектории подачи сигналов Reelin/Apoer2 улучшает воспалительные результаты артрита.

Ремутатоидный артрит (RA) — хроническое аутоиммунное заболевание, характеризующееся синновальным воспалением, образованием паннуса и постепенным совместным разрушением. Вспыльчивая среда в RA приводит к активации эндотелиальных клеток и к повышению регулирования молекул сцепления, что облегчает проникновение лейкоцитов в синовый. Релин, циркулирующий гликопротеин, ранее связанный с активацией эндотели и вербовкой лейкоцитов для лечения таких заболеваний, как атеросклероз и множественный склероз, стал потенциальным регулятором этих процессов. Однако его роль в патогенезе РА остается слабой. Зде

A Narrative Review of Osteonecrosis of the Jaw: What a Clinician Should Know.

Medication-related osteonecrosis of the jaw (MRONJ) is an uncommon complication of antiresorptive therapy (ART) in patients receiving higher and more frequent doses of osteoclast inhibitors. The jaws are the most common site, as they have high bone turnover. The oral structures are exposed to various types of stresses, like mastication and dental diseases, which lead to microtrauma and increased bone remodeling. The hallmark feature of MRONJ is the area of exposed, necrotic, nonhealing, asymptomatic bone for more than eight weeks. Objective signs are pain in the jaw and oral cavity, loose teet

Use of MASCC score in the inpatient management of febrile neutropenia: a single-center retrospective study.

PurposeThe Multinational Association for Supportive Care in Cancer (MASCC) score is used to risk stratify outpatients with febrile neutropenia (FN). However, it is rarely used in hospital settings. We aimed to describe management, use of MASCC score, and outcomes among hospitalized patients with FN.MethodsWe conducted a retrospective cohort study of patients with cancer and FN. We collected patient demographics, cancer characteristics, microbiological profile, MASCC score, utilization of critical care therapies, documentation of goals of care (GOC), and inpatient deaths. Outcomes associated wi

Neuropathic Pain Related with Spinal Disorders: A Systematic Review.

Systematic literature review. To review the evidence from high-quality studies regarding the treatment of neuropathic pain originating specifically from spinal disorders. In general, treatment guidelines for neuropathic pain cover all its various causes, including medical disease, peripheral neuropathy, and cancer. However, the natural history of neuropathic pain originating from spinal disorders may differ from that of the pain originating from other causes or lesions. An expert research librarian used terms related to neuropathic pain and spinal disorders, disc herniation, stenosis, and spin

Targeting the Sonic Hedgehog-Gli1 Pathway as a Potential New Therapeutic Strategy for Myelodysplastic Syndromes.

The complex mechanistic array underlying the pathogenesis of myelodysplastic syndrome (MDS) is still unclear. Although dysregulations of different signaling pathways involved in MDS have been described, the identification of specific biomarkers and therapy targets remains an important task in order to establish novel therapeutic approaches. Here, we demonstrated that the Shh signaling pathway is active in MDS and correlated it with disease progression. Additionally, the knockdown of Gli1 significantly inhibited cell proliferation in vitro and in vivo. Gli1 silencing also induced apoptosis and

The risk of early and late CMV DNAemia associated with Campath use in stem cell transplant recipients.

The risks associated with in vivo and ex vivo use of Campath-1H and -1G in a cohort of 206 stem cell transplant recipients for human CMV (HCMV) DNAemia have been quantified. DNAemia showed a biphasic incidence pattern with an inflexion at day 60. The first phase had a linear risk rate for HCMV DNAemia of 0.3% per day, whereas the second phase had a substantially lower risk rate of 0.058% per day. In multivariable analyses, risk factors for early DNAemia were HCMV serostatus, radiotherapy-based conditioning and CD34 stem cell dose, with the use of in vivo Campath-1H having the most significant

An update on malignant tumor-related stiff person syndrome spectrum disorders: clinical mechanism, treatment, and outcomes.

Stiff person syndrome (SPS) is a rare central nervous system disorder associated with malignancies. In this review, we retrieved information from PubMed, up until August 2023, using various search terms and their combinations, including SPS, stiff person syndrome spectrum disorders (SPSSDs), paraneoplastic, cancer, and malignant tumor. Data from peer-reviewed journals printed in English were organized to explain the possible relationships between different carcinomas and SPSSD subtypes, as well as related autoantigens. From literature searching, it was revealed that breast cancer was the most