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Наркотики, основанные на сходстве генных экспрессионных сигнатур, чтобы исследовать потенциальные признаки кексетина: тематическое исследование множественных склерозов.

Quercetin (QR) — природный флавонол, широко распространенный в королевстве растений с обширными фармакологическими последствиями. Чтобы найти потенциальные клинические показатели QR, 156 Дифференциально выраженные гены (DEG), регулируемые QR, были получены из базы данных Gene Express Omnibus, и новые потенциальные фармакологические эффекты и клинические показатели QR были перенаправлены путем интегрирования соединений с аналогичными генными сигнатурами возмущения и соответствующими сигнатурами болезни QR на основе карты связи и платформ Coexedia. Предлагаемые результаты QR оказывают главным об

Diagnosis and treatment of multisystem amyloidosis associated with SGPL1 mutation: A case report and review of the literature.

RATIONALE: Amyloidosis is a rare, clinically heterogeneous disease, which makes its diagnosis difficult. The relationship between amyloidosis and gene mutations is insufficiently understood. We report a case of sphingosine-1-phosphate lyase 1 (SGPL1) mutation-related amyloidosis, and review the related literature. PATIENT CONCERNS: A 53-year-old man was admitted to our hospital with a 5-month history of renal dysfunction and abdominal distension, aggravated since 2 days. Five months ago, the patient was diagnosed with nephrotic syndrome, with liver dysfunction and abdominal distension. His sy

Воздействие интерферона-β и диметилфумарата на нелинейные динамические характеристики сигнатур электроэнцефалограммы у пациентов с множественным склерозом.

ВВЕДЕНИЕ: Множественный склероз (МС) представляет собой сложное неврологическое состояние, которое затрагивает многих людей во всем мире, и в настоящее время проводится значительный объем исследований, направленных на понимание патологии и развития лечения. Нелинейный анализ все чаще используется для анализа сигналов электроэнцефалографии (ЭЭГ) от пациентов с различными неврологическими расстройствами, включая MS, и он доказал свою эффективность как инструмент понимания сложной природы мозга.МЕТОДЫ: Настоящее исследование направлено на изучение воздействия Интерферона-β (IFN-β) и диметилфумара

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… This drug is administered via injection, and common side effects include flu-like symptoms, injection-site reactions, myalgia, depression, and increased liver enzymes ( Jakimovski et al., 2018 ). Dimethyl fumarate is branded as Tecfidera®. … Interferon-β (IFN-β) Dimethyl fumarate (DMF) Injection Oral Helps reduce inflammation and regulates the immune response Regulates the immune system and prevents stress and inflammation Side effects: flu-like symptoms, injection site reactions, myalgia, depression, and an increase in liver enzymes Side …

Current progress and mechanisms of bone metastasis in lung cancer: a narrative review.

Lung cancer is a kind of malignant tumor with rapid progression and poor prognosis. Distant metastasis has been the main cause of mortality among lung cancer patients. Bone is one of the most common sites. Among all lung cancer patients with bone metastasis, most of them are osteolytic metastasis. Some serious clinical consequences like bone pain, pathological fractures, spinal instability, spinal cord compression and hypercalcemia occur as well. Since the severity of bone metastasis in lung cancer, it is undoubtedly necessary to know how lung cancer spread to bone, how can we diagnose it and

Dibromo-Edaravone Induces Anti-Erythroleukemia Effects via the JAK2-STAT3 Signaling Pathway.

Acute erythroid leukemia (AEL) is a rare and aggressive hematological malignancy managed with chemotherapy, targeted therapies, and stem cell transplantation. However, these treatments often suffer from limitations such as refractoriness, high toxicity, recurrence, and drug resistance, underscoring the urgent need for novel therapeutic approaches. Dibromo-edaravone (D-EDA) is a synthetic derivative of edaravone (EDA) with unreported anti-leukemic properties. In this study, D-EDA demonstrated potent cytotoxicity against HEL cells with an IC50 value of 8.17 ± 0.43 μM using an MTT assay. Morpholo

Clinico-biological significance of suppressor of cytokine signaling 1 expression in acute myeloid leukemia.

Suppressor of cytokine signaling 1 (SOCS1) protein, which encodes a member of signal transducers and activators of transcription-induced inhibitors, takes part in a negative regulation of cytokine signaling. The mechanism of SOCS1 in tumor carcinogenesis is complex and there have been no studies concerning the clinic-biologic implication of SOCS1 expression in acute myeloid leukemia (AML). Here, we first identified that higher bone marrow (BM) SOCS1 expression was closely associated with older age, FLT3-ITD, NPM1 and DNMT3A mutations, but negatively correlated with CEBPA mutation in patients w

EMD originates from hyaluronan-induced homophilic interactions of CD44 variant-expressing MM cells under shear stress.

Extramedullary disease (EMD) is known to be associated with chemoresistance and poor prognosis in multiple myeloma (MM); however, the mechanisms of its development are not fully understood. Elucidating the mechanism of EMD development and its therapeutic targeting would greatly contribute to further improvement of treatment outcome in patients with MM. Here, we show that bone marrow stroma cell-derived hyaluronan (HA) elicits homophilic interactions of MM cells by binding to surface CD44, especially long-stretch variants, under physiological shear stress and generates cell clusters that might

Диет модернизирует терапевтическое воздействие диметилфумарата, поддерживаемого иммунометаболическим нейтрофильным рецептором HCAR2.

Монометилфумарат (ММФ) и его пронаркодиметилфумарат (ДМП) в настоящее время являются наиболее широко используемыми агентами для лечения множественных склерозов (МС). Однако не все пациенты получают помощь от ДМФ. Мы предположили, что переменная реакция пациентов может быть связана с их питанием. В поддержку этой гипотезы мыши, подвергшиеся экспериментальному аутоиммунальному энцефаломиэлиту (EAE), являющемуся моделью MS, не пользовались лечением DMF при питании богатой лауричной кислотой диетой. В противоположность этому, мыши на нормальном питании чау (NC) и даже мыши на рационе с высоким сод

Balancing the Scales: The Dual Role of Interleukins in Bone Metastatic Microenvironments.

Bone metastases, a common and debilitating consequence of advanced cancers, involve a complex interplay between malignant cells and the bone microenvironment. Central to this interaction are interleukins (ILs), a group of cytokines with critical roles in immune modulation and inflammation. This review explores the dualistic nature of pro-inflammatory and anti-inflammatory interleukins in bone metastases, emphasizing their molecular mechanisms, pathological impacts, and therapeutic potential. Pro-inflammatory interleukins, such as IL-1, IL-6, and IL-8, have been identified as key drivers in pro

Limited Clinical Efficacy with Potential Adverse Events in a Pilot Study of Autologous Adoptive Cell Therapy in Canine Oral Malignant Melanoma.

Adoptive cell therapy (ACT) has been studied in several human and canine cancers with some promising clinical outcomes but not in canine oral malignant melanoma (OMM). Our manuscript aimed to explore one kind of ACT, the ex vivo-expanded autologous immune cell infusion in canine OMM, as this tumor remains a treatment dilemma. The study recruited dogs with histopathological diagnoses of oral malignant melanoma, generated their peripheral blood mononuclear cells, expanded them into predominantly non-B non-T cells via stimulations of IL-15, IL-2, and IL-21, and then re-infused the cells into tumo

Combination with third-generation bisphosphonate (YM529) and interferon-alpha can inhibit the progression of established bone renal cell carcinoma.

The aim of this study was to investigate whether the third-generation nitrogen-containing bisphosphonate (YM529) can inhibit the progression of established bone renal cell carcinoma (RCC) and to elucidate its mechanism. Antiproliferative effect and apoptosis induction of RCC cells and mouse osteoclasts by YM529 and/or interferon-alpha (IFN-α) were evaluated in vitro using cell counting and in vivo using soft X-ray, the TUNEL method and tartrate-resistant acid phosphatase stain. For the in vivo study, male athymic BALB/cA Jc1-nu nude mice bearing human RCC cell line RBM1-IT4 cells were treated

2022 Chinese expert consensus and guidelines on clinical management of toxicity in anti-CD19 chimeric antigen receptor T-cell therapy for B-cell non-Hodgkin lymphoma.

Adoptive cellular immunotherapy with chimeric antigen receptor (CAR) T cells has emerged as a novel modality for treating relapsed and/or refractory B-cell non-Hodgkin lymphoma (B-NHL). With increasing approval of CAR T-cell products and advances in CAR T cell therapy, CAR T cells are expected to be used in a growing number of cases. However, CAR T-cell-associated toxicities can be severe or even fatal, thus compromising the survival benefit from this therapy. Standardizing and studying the clinical management of these toxicities are imperative. In contrast to other hematological malignancies,

Synergistic Effects of Olfactory Ecto-Mesenchymal Stem Cell Supernatant and Ellagic Acid on Demyelination and Glial Modulation in a Chronic Multiple Sclerosis Model.

Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system. Stem cells as a source of neurotrophic factors and ellagic acid (EA) as an antioxidant reduce the progression of neurodegenerative diseases. In this study, we evaluated the effect of olfactory ecto-mesenchymal stem cell (EMSC) supernatant and EA on A1 astrocytes, M1 microglia, and demyelination in cuprizone model. To induce the chronic demyelination model, mice received a diet containing 0.2% cuprizone/kg of food for 12 weeks. EMSC supernatant was injected into the lateral ventricle of mice. EA was

Derivation and elimination of uremic toxins from kidney-gut axis.

Uremic toxins are chemicals, organic or inorganic, that accumulate in the body fluids of individuals with acute or chronic kidney disease and impaired renal function. More than 130 uremic solutions are included in the most comprehensive reviews to date by the European Uremic Toxins Work Group, and novel investigations are ongoing to increase this number. Although approaches to remove uremic toxins have emerged, recalcitrant toxins that injure the human body remain a difficult problem. Herein, we review the derivation and elimination of uremic toxins, outline kidney-gut axis function and relati

Efficacy and Safety of Acupuncture Combined with Conventional Drug Therapy for the Treatment of Cancer-Induced Bone Pain: A Network Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Cancer-induced bone pain (CIBP) involves both nociceptive and neuropathic components, causing significant suffering in cancer patients. Acupuncture has shown beneficial effects on CIBP. However, given the diverse acupuncture techniques, their therapeutic efficacy may vary. OBJECTIVE: To evaluate the efficacy and safety of various acupuncture modalities integrated with conventional drug therapy for CIBP. METHODS: Randomized controlled trials (RCTs) of acupuncture combined with conventional analgesics for CIBP were searched across eight Chinese and English databases and clinical tr

High mobility group box 1 induces bone pain associated with bone invasion in a mouse model of advanced head and neck cancer.

Advanced head and neck cancer (HNC) can invade facial bone and cause bone pain, thus posing a significant challenge to the quality of life of patients presenting with advanced HNC. The present study was designed to investigate HNC bone pain (HNC‑BP) in an intratibial mouse xenograft model that utilized an HNC cell line (SAS cells). These mice develop HNC‑BP that is associated with an expression of phosphorylated ERK1/2 (pERK1/2), which is a molecular indicator of neuron excitation in dorsal root ganglia (DRG) sensory neurons. Our experiments demonstrated that the inhibition of high mobility gr

RXR Agonists Enhance Lenalidomide Anti-Myeloma Activity and T Cell Functions while Retaining Glucose-Lowering Effect.

Retinoid X receptor (RXR) heterodimerizes with the PPAR nuclear hormone receptor and regulates its downstream events. We investigated the effects of RXR agonists (LG100754, bexarotene, AGN194204, and LG101506) on lenalidomide's anti-myeloma activity, T cell functions, and the level of glucose and lipids in vivo. Genetic overexpression and CRISPR/Cas9 knockout experiments were conducted in multiple myeloma (MM) cell lines and Jurkat T cell lines to determine the roles of CRBN in RXR-agonist mediated effects. A xenograft mouse model of MM was established to determine the combination effect of LG

Efficacy and safety of oncolytic virus combined with chemotherapy or immune checkpoint inhibitors in solid tumor patients: A meta-analysis.

Background: In recent years, several clinical trials have focused on oncolytic virus (OVs) combined with chemotherapy or immune checkpoint inhibitors (ICIs) in solid tumor patients, which showed encouraging effects. However, few studies have concentrated on the summary on the safety and efficacy of the combined treatments. Therefore, we conducted this meta-analysis to explore the safety and curative effect of the combined therapy. Methods: We searched the PubMed, Cochrane Library, Embase, and Clinicaltrials.gov databases to comprehensively select articles on OVs combined with chemotherapy or I

Clinical outcomes of chemotherapy in cancer patients with different ethnicities.

BackgroundChoosing the most effective chemotherapeutic agent with safest side effect profile is a common challenge in cancer treatment. Although there are standardized chemotherapy protocols in place, protocol changes made after extensive clinical trials demonstrate significant improvement in the efficacy and tolerability of certain drugs. The pharmacokinetics, pharmacodynamics, and tolerance of anti-cancer medications are all highly individualized. A driving force behind these differences lies within a person's genetic makeup.Recent findingsPharmacogenomics, the study of how an individual's g

Advances in Molecularly Imprinted Polymers for Bone Biomarker Detection and Therapeutic Applications.

This review explores the application of molecularly imprinted polymers (MIPs) in detecting bone turnover biomarkers and advancing osteogenic treatment strategies. MIPs, designed to mimic biological recognition sites, offer innovative solutions for precise molecular recognition in bone health management. Chemical methodologies for MIPs synthesis and their integration into diagnostic systems for detecting bone resorption markers are highlighted. Furthermore, MIP-driven therapeutic advancements, including controlled drug release, cell imprinting for osteogenic differentiation, and functional scaf