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Aminopeptidase N: a multifunctional and promising target in medicinal chemistry.

Aminopeptidase N (APN) is a zinc metalloproteinase present in almost all types of organisms and has various functions. Many of them are unrelated to its catalytic activity, which is why APN is sometimes classified as a moonlighting enzyme. APN is involved in carcinogenesis and angiogenesis. It also works as an entrance receptor for some coronaviruses and acts as a mediator during skin inflammation. Additionally, APN removes and helps to recycle regulatory proteins including neuropeptides, which is why its inhibitors hold therapeutic potential for a wide range of diseases, making the design and

MDM2/X Inhibitors as Radiosensitizers for Glioblastoma Targeted Therapy.

Inhibition of the MDM2/X-p53 interaction is recognized as a potential anti-cancer strategy, including the treatment of glioblastoma (GB). In response to cellular stressors, such as DNA damage, the tumor suppression protein p53 is activated and responds by mediating cellular damage through DNA repair, cell cycle arrest and apoptosis. Hence, p53 activation plays a central role in cell survival and the effectiveness of cancer therapies. Alterations and reduced activity of p53 occur in 25-30% of primary GB tumors, but this number increases drastically to 60-70% in secondary GB. As a result, reacti

Tumor Cell Survival Factors and Angiogenesis in Chronic Lymphocytic Leukemia: How Hot Is the Link?

Chronic lymphocytic leukemia (CLL) is characterized by the accumulation of neoplastic CD5+/CD19+ B lymphocytes in the blood. These cells migrate to and proliferate in the bone marrow and lymphoid tissues. Despite the development of new therapies for CLL, drug resistance and disease relapse still occur; novel treatment approaches are therefore still needed. Inhibition of the angiogenesis involved in the progression of CLL might be a relevant therapeutic strategy. The literature data indicate that vascular endothelial growth factor, angiopoietin-2, and matrix metalloproteinase-9 are pro-angiogen

Exploiting the Ref-1-APE1 node in cancer signaling and other diseases: from bench to clinic.

Reduction-oxidation factor 1-apurinic/apyrimidinic endonuclease (Ref-1/APE1) is a critical node in tumor cells, both as a redox regulator of transcription factor activation and as part of the DNA damage response. As a redox signaling protein, Ref-1/APE1 enhances the transcriptional activity of STAT3, HIF-1α, nuclear factor kappa B, and other transcription factors to promote growth, migration, and survival in tumor cells as well as inflammation and angiogenesis in the tumor microenvironment. Ref-1/APE1 is activated in a variety of cancers, including prostate, colon, pancreatic, ovarian, lung an

Review of COVID-19 Therapeutics by Mechanism: From Discovery to Approval.

The global research and pharmaceutical community rapidly mobilized to develop treatments for coronavirus disease 2019 (COVID-19). Existing treatments have been repurposed and new drugs have emerged. Here we summarize mechanisms and clinical trials of COVID-19 therapeutics approved or in development. Two reviewers, working independently, reviewed published data for approved COVID-19 vaccines and drugs, as well as developmental pipelines, using databases from the following organizations: United States Food and Drug Administration (US-FDA), European Medicines Agency (EMA), Japanese Pharmaceutical

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… Target proteases of conestat alfa are involved in the activation of complement protein C1, kallikrein, factor XIIa, and factor XIa. 90 Activation of the complement system plays a central role in the pathogenesis of acute lung injury. …

Another Weapon against Cancer and Metastasis: Physical-Activity-Dependent Effects on Adiposity and Adipokines.

Physically active behavior has been associated with a reduced risk of developing certain types of cancer and improved psychological conditions for patients by reducing anxiety and depression, in turn improving the quality of life of cancer patients. On the other hand, the correlations between inactivity, sedentary behavior, and overweight and obesity with the risk of development and progression of various cancers are well studied, mainly in middle-aged and elderly subjects. In this article, we have revised the evidence on the effects of physical activity on the expression and release of the ad

Interleukin-1 Beta-A Friend or Foe in Malignancies?

Interleukin-1 beta (IL-1β) is induced by inflammatory signals in a broad number of immune cell types. IL-1β (and IL-18) are the only cytokines which are processed by caspase-1 after inflammasome-mediated activation. This review aims to summarize current knowledge about parameters of regulation of IL-1β expression and its multi-facetted role in pathophysiological conditions. IL-1 signaling activates innate immune cells including antigen presenting cells, and drives polarization of CD4+ T cells towards T helper type (Th) 1 and Th17 cells. Therefore, IL-1β has been attributed a largely beneficial

МикроРН в связи с иммунными заболеваниями: механизм, функции и терапевтические аспекты.

МикроРНК (миРНК) представляют собой эволюционно сохранившиеся, некодирующие молекулы РНК приблизительно 18-25 нуклеотидов по длине, которые регулируют генное выражение на посттранарном уровне. Их главным механизмом действий является пост-ранарное заглушение генов с помощью интерференции РНК, которое достигается путем привязки к дополнительным последовательности в рамках целевых посыльных РНК (mRNA). Накопляемые данные свидетельствуют о ключевой роли miRNA в развитии, дифференциации и функционировании иммунных клеток, а также в сохранении иммунной гомеостазии. Более полное понимание сложных мол

Biomarker-Driven Approaches to Bone Metastases: From Molecular Mechanisms to Clinical Applications.

Bone metastases represent a critical complication in oncology, frequently indicating advanced malignancy and substantially reducing patient quality of life. This review provides a comprehensive analysis of the complex interactions between tumor cells and the bone microenvironment, emphasizing the relevance of the "seed and soil" hypothesis, the RANK/RANKL/OPG signaling axis, and Wnt signaling pathways that collectively drive metastatic progression. The molecular and cellular mechanisms underlying the formation of osteolytic and osteoblastic lesions are examined in detail, with a particular foc

Molecular mechanisms and clinical management of cancer bone metastasis.

As one of the most common metastatic sites of malignancies, bone has a unique microenvironment that allows metastatic tumor cells to grow and flourish. The fenestrated capillaries in the bone, bone matrix, and bone cells, including osteoblasts and osteoclasts, together maintain the homeostasis of the bone microenvironment. In contrast, tumor-derived factors act on bone components, leading to subsequent bone resorption or excessive bone formation. The various pathways involved also provide multiple targets for therapeutic strategies against bone metastases. In this review, we summarize the curr

Tumor Microenvironment Onmyoji: Cytokines with Dual Protumor and Antitumor Roles.

Cytokines are essential components of the tumor microenvironment (TME) and play crucial roles in tumor initiation and progression. As key mediators of interactions between immune cells and tumor cells within the TME, many cytokines exhibit both protumor and antitumor properties. This complex duality, reminiscent of the balance philosophy pursued by "Onmyoji" in traditional Eastern philosophy, which involves observing and regulating opposing forces to achieve harmony, poses marked challenges in translating cytokine therapies from animal studies to clinical applications. More than 20 key cytokin

Role of Proteins in Oncology: Advances in Cancer Diagnosis, Prognosis, and Targeted Therapy-A Narrative Review.

Modern oncology increasingly relies on the role of proteins as key components in cancer diagnosis, prognosis, and targeted therapy. This review examines advancements in protein biomarkers across several cancer types, including breast cancer, lung cancer, ovarian cancer, and hepatocellular carcinoma. These biomarkers have proven critical for early detection, treatment response monitoring, and tailoring personalized therapeutic strategies. The article highlights the utility of targeted therapies, such as tyrosine kinase inhibitors and monoclonal antibodies, in improving treatment efficacy while

Beyond boundaries: unraveling innovative approaches to combat bone-metastatic cancers.

Evidence demonstrated that bones, liver, and lungs are the most common metastasis sites in some human malignancies, especially in prostate and breast cancers. Bone is the third most frequent target for spreading tumor cells among these organs and tissues. Patients with bone-metastatic cancers face a grim prognosis characterized by short median survival time. Current treatments have proven insufficient, as they can only inhibit metastasis or tumor progression within the bone tissues rather than providing a curative solution. Gaining a more profound comprehension of the interplay between tumor c

An Extensive Review on Preclinical and Clinical Trials of Oncolytic Viruses Therapy for Pancreatic Cancer.

Chemotherapy resistance and peculiar tumor microenvironment, which diminish or mitigate the effects of therapies, make pancreatic cancer one of the deadliest malignancies to manage and treat. Advanced immunotherapies are under consideration intending to ameliorate the overall patient survival rate in pancreatic cancer. Oncolytic viruses therapy is a new type of immunotherapy in which a virus after infecting and lysis the cancer cell induces/activates patients' immune response by releasing tumor antigen in the blood. The current review covers the pathways and molecular ablation that take place

Current advance of nanotechnology in diagnosis and treatment for malignant tumors.

Cancer remains a significant risk to human health. Nanomedicine is a new multidisciplinary field that is garnering a lot of interest and investigation. Nanomedicine shows great potential for cancer diagnosis and treatment. Specifically engineered nanoparticles can be employed as contrast agents in cancer diagnostics to enable high sensitivity and high-resolution tumor detection by imaging examinations. Novel approaches for tumor labeling and detection are also made possible by the use of nanoprobes and nanobiosensors. The achievement of targeted medication delivery in cancer therapy can be acc

Epigenetic modifications in early stage lung cancer: pathogenesis, biomarkers, and early diagnosis.

The integration of liquid biopsy with epigenetic markers offers significant potential for early lung cancer detection and personalized treatment. Epigenetic alterations, including DNA methylation, histone modifications, and noncoding RNA changes, often precede genetic mutations and are critical in cancer progression. In this study, we explore how liquid biopsy, combined with epigenetic markers, can provide early detection of lung cancer, potentially predicting onset up to 4 years before clinical diagnosis. We discuss the challenges of targeting epigenetic regulators, which could disrupt cellul

Is stroke incidence increased in survivors of adult cancers? A systematic review and meta-analysis.

PurposeExisting research hints that people living with and beyond cancer are at an increased risk of stroke. However, there is insufficient evidence to appropriately inform guidelines for specific stroke prevention or management for cancer patients. We conducted a systematic review and meta-analysis to describe and quantify stroke incidence in people living with and beyond cancer.MethodsMedline, CINAHL, and EMBASE were searched for epidemiological studies comparing stroke incidence between cancer and non-cancer patients. Reviewers independently extracted data; random-effects meta-analyses and

Effects of Physical Cues on Stem Cell-Derived Extracellular Vesicles toward Neuropathy Applications.

The peripheral nervous system undergoes sufficient stress when affected by diabetic conditions, chemotherapeutic drugs, and personal injury. Consequently, peripheral neuropathy arises as the most common complication, leading to debilitating symptoms that significantly alter the quality and way of life. The resulting chronic pain requires a treatment approach that does not simply mask the accompanying symptoms but provides the necessary external environment and neurotrophic factors that will effectively facilitate nerve regeneration. Under normal conditions, the peripheral nervous system self-r

Nanoparticles and bone microenvironment: a comprehensive review for malignant bone tumor diagnosis and treatment.

Malignant bone tumors, which are difficult to treat with current clinical strategies, originate from bone tissues and can be classified into primary and secondary types. Due to the specificity of the bone microenvironment, the results of traditional means of treating bone tumors are often unsatisfactory, so there is an urgent need to develop new treatments for malignant bone tumors. Recently, nanoparticle-based approaches have shown great potential in diagnosis and treatment. Nanoparticles (NPs) have gained significant attention due to their versatility, making them highly suitable for applica

Endothelial dysfunction in congenital adrenal hyperplasia due to 21-hydroxylase deficiency: current knowledge and novel biomarkers.

Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (21OHD) is a complex endocrine disorder characterized by impaired cortisol synthesis and androgen excess. Beyond its hormonal and metabolic implications, CAH has been increasingly associated with an elevated risk of cardiovascular complications, including endothelial dysfunction, a critical precursor to atherosclerosis and a risk factor for cardiovascular and metabolic diseases. This review explores the current knowledge on endothelial function in patients with CAH, focusing on the interplay between chronic hormonal imbalanc