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Interleukin-6 in Hepatocellular Carcinoma: A Dualistic Point of View.

Hepatocellular Carcinoma (HCC) is a pressing health concern, demanding a deep understanding of various mediators' roles in its development for therapeutic progress. Notably, interleukin-6 (IL-6) has taken center stage in investigations due to its intricate and context-dependent functions. This review delves into the dual nature of IL-6 in HCC, exploring its seemingly contradictory roles as both a promoter and an inhibitor of disease progression. We dissect the pro-tumorigenic effects of IL-6, including its impact on tumor growth, angiogenesis, and metastasis. Concurrently, we examine its anti-

The Role of TAM Receptors in Bone.

The TAM (TYRO3, MERTK, and AXL) family of receptor tyrosine kinases are pleiotropic regulators of adult tissue homeostasis maintaining organ integrity and self-renewal. Disruption of their homeostatic balance fosters pathological conditions like autoinflammatory or degenerative diseases including rheumatoid arthritis, lupus erythematodes, or liver fibrosis. Moreover, TAM receptors exhibit prominent cell-transforming properties, promoting tumor progression, metastasis, and therapy resistance in various cancer entities. Emerging evidence shows that TAM receptors are involved in bone homeostasis

Микробиота человека в области здравоохранения и отдельные раковые заболевания.

Большинство эпителиальных поверхностей нашего тела, пищеварительный тракт, дыхательные и врожденные системы, колонизируются большим количеством бактерий, археи, грибов, протозоанов и вирусов. Эти микробиота, особенно кишки, играют важную и полезную роль в пищеварении, метаболизме и синтезе витаминов. Их метаболиты стимулируют производство цитокина человеком, которое используется против потенциальных патогенов. На состав микробиоты влияет ряд внутренних и внешних факторов, включая питание, возраст, болезни и образ жизни. Такие изменения, называемые дисбиозом, могут быть связаны с развитием разл

Overview of Dual-Acting Drug Methotrexate in Different Neurological Diseases, Autoimmune Pathologies and Cancers.

Methotrexate, a structural analogue of folic acid, is one of the most effective and extensively used drugs for treating many kinds of cancer or severe and resistant forms of autoimmune diseases. In this paper, we take an overview of the present state of knowledge with regards to complex mechanisms of methotrexate action and its applications as immunosuppressive drug or chemotherapeutic agent in oncological combination therapy. In addition, the issue of the potential benefits of methotrexate in the development of neurological disorders in Alzheimer's disease or myasthenia gravis will be discuss

Убиквитационное регулирование гликолитического фермента MCT4 в поощрении астроцитной реактивности во время нейроинфламмации.

Одним из гистопатологических признаков нервно-воспалительных заболеваний, таких, как множественный склероз (MS), является появление астроцитной реактивности. Накопление данных свидетельствует о том, что чрезмерный гликолиз может привести к астроцитной реактивности и способствовать нейроэнфламативным реакциям. Однако сложные механизмы, лежащие в основе метаболического перепрограммирования астроцитов в направлении гликолиза, остаются в значительной степени неизвестными. Здесь мы провели эксперименты in vitro с использованием первичных астроцитов и в vivo в экспериментальной аутоиммунной энцефало

Exosomes in the Repair of Bone Defects: Next-Generation Therapeutic Tools for the Treatment of Nonunion.

Nonunion with bone defects, a common complication after long bone fracture, is a major challenge for orthopaedic surgeons worldwide because of the high incidence rate and difficulties in achieving successful treatment. Bone defects are the main complications of nonunion. The conventional biological treatments for nonunion with bone defects involve the use of autologous bone grafts or bone graft substitutes and cell-based therapy. Traditional nonunion treatments have always been associated with safety issues and various other complications. Bone grafts have limited autologous cancellous bone an

The Bone Marrow Microenvironment Mechanisms in Acute Myeloid Leukemia.

Bone marrow (BM) is a highly complex tissue that provides important regulatory signals to orchestrate hematopoiesis. Resident and transient cells occupy and interact with some well characterized niches to produce molecular and cellular mechanisms that interfere with differentiation, migration, survival, and proliferation in this microenvironment. The acute myeloid leukemia (AML), the most common and severe hematological neoplasm in adults, arises and develop in the BM. The osteoblastic, vascular, and reticular niches provide surface co-receptors, soluble factors, cytokines, and chemokines that

Signaling pathways in the regulation of cytokine release syndrome in human diseases and intervention therapy.

Cytokine release syndrome (CRS) embodies a mixture of clinical manifestations, including elevated circulating cytokine levels, acute systemic inflammatory symptoms and secondary organ dysfunction, which was first described in the context of acute graft-versus-host disease after allogeneic hematopoietic stem-cell transplantation and was later observed in pandemics of influenza, SARS-CoV and COVID-19, immunotherapy of tumor, after chimeric antigen receptor T (CAR-T) therapy, and in monogenic disorders and autoimmune diseases. Particularly, severe CRS is a very significant and life-threatening co

Non-Exosomal and Exosomal Circulatory MicroRNAs: Which Are More Valid as Biomarkers?

MicroRNAs (miRNAs) are a group of small non-coding RNAs with approximately 19-25 nucleotides that are involved in regulating a range of developmental and physiological processes. Non-exosomal circulating and exosomal miRNAs have also been proposed to be useful in diagnostics as biomarkers for diseases and different types of cancer. In this review, the quantity of miRNAs and of reliable experimental data analyses of miRNAs that come from exosomal and non-exosomal sources are discussed from the perspective of their use as biomarkers for cancer and other diseases, including viral infections, nerv

Combination therapy in combating cancer.

Combination therapy, a treatment modality that combines two or more therapeutic agents, is a cornerstone of cancer therapy. The amalgamation of anti-cancer drugs enhances efficacy compared to the mono-therapy approach because it targets key pathways in a characteristically synergistic or an additive manner. This approach potentially reduces drug resistance, while simultaneously providing therapeutic anti-cancer benefits, such as reducing tumour growth and metastatic potential, arresting mitotically active cells, reducing cancer stem cell populations, and inducing apoptosis. The 5-year survival

Advances in microsurgery and assisted reproduction for management of male infertility.

BACKGROUND: This study examines genetic diversity among 102 registered English Bulldogs used for breeding based on maternal and paternal haplotypes, allele frequencies in 33 highly polymorphic short tandem repeat (STR) loci on 25 chromosomes, STR-linked dog leukocyte antigen (DLA) class I and II haplotypes, and the number and size of genome-wide runs of homozygosity (ROH) determined from high density SNP arrays. The objective was to assess whether the breed retains enough genetic diversity to correct the genotypic and phenotypic abnormalities associated with poor health, to allow for the elimi

Contemporary Monoclonal Antibody Utilization in Glomerular Diseases.

Therapeutic monoclonal antibodies (MAbs) have been one of the fastest growing drug classes in the past 2 decades and are indicated in the treatment of cancer, autoimmune disorders, solid organ transplantation, and glomerular diseases. The Food and Drug Administration has approved 100 MAbs between 1986 and 2021, and MAbs account for 20% of Food and Drug Administration's new drug approval every year. MAbs are preferred over traditional immunosuppressive agents because of their high specificity, reduced number of drug-drug interactions, and low toxicity, which make them a prime example of persona

Trichloroethylene: An Invisible Cause of Parkinson's Disease?

The etiologies of Parkinson's disease (PD) remain unclear. Some, such as certain genetic mutations and head trauma, are widely known or easily identified. However, these causes or risk factors do not account for the majority of cases. Other, less visible factors must be at play. Among these is a widely used industrial solvent and common environmental contaminant little recognized for its likely role in PD: trichloroethylene (TCE). TCE is a simple, six-atom molecule that can decaffeinate coffee, degrease metal parts, and dry clean clothes. The colorless chemical was first linked to parkinsonism

Распознавание ксантиновой реберосколочной структуры и металлическое ионопосредованное распознавание лиганда.

Рибосколки сохраняют функциональные области в MRNA, которые в основном существуют в бактериях. Они регулируют генное выражение в ответ на различные концентрации метаболитов или металлических ионов. Недавно был выявлен мотив РНК NMT1 для селективной привязки ккантиновой и мочевой кислот, соответственно, к метаболическому пути деградации пурины. Вот, мы сообщаем о кристаллической структуре этой РНК, связанной с ксантиной. В целом рибосуха имеет стержень, постоянно сложенный в сложенном виде three стебли и two внутренние перекрестки. Связующий карман определяется высокоохранной соединенной послед

The Application Progress of Patient-Derived Tumor Xenograft Models After Cholangiocarcinoma Surgeries.

Surgical treatment is the only possible cure for cholangiocarcinoma (CCA) at present. However, the high recurrence rate of postoperative CCA leads to a very poor prognosis for patients, effective postoperative chemotherapy is hence the key to preventing the recurrence of CCA. The sensitivity of CCA to cytotoxic chemotherapy drugs and targeted drugs varies from person to person, and therefore, the screening of sensitive drugs has become an important topic after CCA surgeries. Patient-Derived tumor Xenograft models (PDX) can stably retain the genetic and pathological characteristics of primary t

The Role of Drug Repurposing in the Development of Novel Antimicrobial Drugs: Non-Antibiotic Pharmacological Agents as Quorum Sensing-Inhibitors.

Background: The emergence of multidrug-resistant organisms (MDROs) is a global public health issue, severely hindering clinicians in administering appropriate antimicrobial therapy. Drug repurposing is a drug development strategy, during which new pharmacological applications are identified for already approved drugs. From the viewpoint of the development of virulence inhibitors, inhibition of quorum sensing (QS) is a promising route because various important features in bacterial physiology and virulence are mediated by QS-dependent gene expression. Methods: Forty-five pharmacological agents,

Targeting Selectins and Their Ligands in Cancer.

Aberrant glycosylation is a hallmark of cancer cells with increased evidence pointing to a role in tumor progression. In particular, aberrant sialylation of glycoproteins and glycolipids has been linked to increased immune cell evasion, drug evasion, drug resistance, tumor invasiveness, and vascular dissemination, leading to metastases. Hypersialylation of cancer cells is largely the result of overexpression of sialyltransferases (STs). Differentially, humans express twenty different STs in a tissue-specific manner, each of which catalyzes the attachment of sialic acids via different glycosidi

Voltage-gated sodium channel as a target for metastatic risk reduction with re-purposed drugs.

ObjectiveTo determine the exact role of sodium channel proteins in migration, invasion and metastasis and understand the possible anti-invasion and anti-metastatic activity of repurposed drugs with voltage gated sodium channel blocking properties.Material and methodsA review of the published medical literature was performed searching for pharmaceuticals used in daily practice, with inhibitory activity on voltage gated sodium channels. For every drug found, the literature was reviewed in order to define if it may act against cancer cells as an anti-invasion and anti-metastatic agent and if it w

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… Sodium channels are glycosylated transmembrane proteins that form passages in the cell membrane for the penetration of sodium into the intracellular space according to their electrical gradients. …

Small compound 6-O-angeloylplenolin induces mitotic arrest and exhibits therapeutic potentials in multiple myeloma.

BackgroundMultiple myeloma (MM) is a disease of cell cycle dysregulation while cell cycle modulation can be a target for MM therapy. In this study we investigated the effects and mechanisms of action of a sesquiterpene lactone 6-O-angeloylplenolin (6-OAP) on MM cells.Methodology/principal findingsMM cells were exposed to 6-OAP and cell cycle distribution were analyzed. The role for cyclin B1 to play in 6-OAP-caused mitotic arrest was tested by specific siRNA analyses in U266 cells. MM.1S cells co-incubated with interleukin-6 (IL-6), insulin-like growth factor-I (IGF-I), or bone marrow stromal

Nucleic acid aptamers in orthopedic diseases: promising therapeutic agents for bone disorders.

Precision medicine has become a cornerstone in modern therapeutic strategies, with nucleic acid aptamers emerging as pivotal tools due to their unique properties. These oligonucleotide fragments, selected through the Systematic Evolution of Ligands by Exponential Enrichment process, exhibit high affinity and specificity toward their targets, such as DNA, RNA, proteins, and other biomolecules. Nucleic acid aptamers offer significant advantages over traditional therapeutic agents, including superior biological stability, minimal immunogenicity, and the capacity for universal chemical modificatio