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Iron deprivation in cancer--potential therapeutic implications.

Iron is essential for normal cellular function. It participates in a wide variety of cellular processes, including cellular respiration, DNA synthesis, and macromolecule biosynthesis. Iron is required for cell growth and proliferation, and changes in intracellular iron availability can have significant effects on cell cycle regulation, cellular metabolism, and cell division. Perhaps not surprisingly then, neoplastic cells have been found to have higher iron requirements than normal, non-malignant cells. Iron depletion through chelation has been explored as a possible therapeutic intervention i

Ferret coronavirus-associated diseases.

A novel coronavirus of ferrets was first described in 1993. This coronavirus caused an enteric disease called epizootic catarrhal enteritis (ECE). Recently, a ferret systemic coronavirus (FRSCV)-associated disease was discovered. This new systemic disease resembles the dry form of feline infectious peritonitis (FIP) and has been reported in the United States and Europe. This article addresses the clinical signs, pathology, pathogenesis, diagnosis, treatment, and prevention of this ferret FIP-like disease.

Genome Editing Approaches with CRISPR/Cas9 for Cancer Treatment: Critical Appraisal of Preclinical and Clinical Utility, Challenges, and Future Research.

The increasing burden on human malignant diseases became a major concern for healthcare practitioners, that must deal with tumor relapse and the inability to efficiently treat metastasis, in addition to side effects. Throughout the decades, many therapeutic strategies have been employed to improve the clinical outcomes of cancer patients and great efforts have been made to develop more efficient and targeted medicines. The malignant cell is characterized by genetic and epigenetic modifications, therefore targeting those specific drivers of carcinogenesis is highly desirable. Among the genome e

Beyond DNA Damage: Exploring the Immunomodulatory Effects of Cyclophosphamide in Multiple Myeloma.

The alkylating agent cyclophosphamide has been used in the treatment of multiple myeloma for over 60 years. At low doses, cyclophosphamide also has significant immunomodulatory activity, which can be used to modify the immunosuppressive tumor microenvironment in order to augment responses to existing therapies. Immune-mediated therapies are becoming more widespread in modern approaches to myeloma treatment. In this review, we discuss the effects cyclophosphamide has on the immune system, and how it can be used synergistically with other treatment modalities including the immunomodulatory agent

Abscopal Effect in Radiation Therapy: The Immune Mechanisms and Clinical Advances.

The abscopal effect is a systemic antitumor response to localized radiotherapy (RT) that has emerged as a central focus in the era of immunotherapy. Clinical evidence demonstrates that local RT can induce regression of distant, nonirradiated metastases, including cases of complete remission. However, the effect remains unpredictable, with marked variation in clinical outcomes ranging from complete regression to paradoxical progression. The mechanistic basis for this heterogeneity and optimal strategies to enhance abscopal effects remain incompletely understood. This review synthesizes current

HERV-W Env вызывает нейронный пироптоз с помощью NLRP3-CASP1-GSDMD Pathway в недавней Шизофрении.

HERVs (человеческие эндогенные ретровирусы) являются остатками древних внешних ретровирусов, которые интегрировались в геном человека, особенно в микробных клетках. Среди них белковый ген HERV-Wenv (Human Internal revoiruses W семейный белок), расположенный на хромосоме 7 и выраженный главным образом в плаценте человека, тесно связан с различными нейропсихиатрическими расстройствами, включая шизофрению, а также аутоиммунные заболевания и рак. Недавние исследования выявили аномальное выражение цитокина в качестве ключевого фактора в патофизиологии шизофрении. В частности, повышенные уровни сыво

Targeting of multiple myeloma-related angiogenesis by miR-199a-5p mimics: in vitro and in vivo anti-tumor activity.

Multiple myeloma (MM) cells induce relevant angiogenic effects within the human bone marrow milieu (huBMM) by the aberrant expression of angiogenic factors. Hypoxia triggers angiogenic events within the huBMM and the transcription factor hypoxia-inducible factor-1α (HIF-1α) is over-expressed by MM cells. Since synthetic miR-199a-5p mimics negatively regulates HIF-1α, we here investigated a miRNA-based therapeutic strategy against hypoxic MM cells. We indeed found that enforced expression of miR-199a-5p led to down-modulated expression of HIF-1α as well as of other pro-angiogenic factors such a

Recent advances in precision oncology research.

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Tumor-educated leukocytes mRNA as a diagnostic biomarker for non-small cell lung cancer.

BackgroundThis study aimed to investigate the diagnostic and prognostic role of tumor-educated leukocytes (TELs) mRNA in Chinese patients with non-small cell lung cancer (NSCLC).MethodsThe TELs collected underwent total RNA isolation. RNA-sequencing (RNA-seq) technology was used to analyze the transcriptome of the TELs. The mRNA expression levels of differential genes were analyzed by RT-qPCR. Statistical analyses were performed using Prism and SPSS by Mann-Whitney nonparametric test, Kruskal-Wallis test and one-way ANOVA.ResultsWe used RNA-seq technology to screen 95 differential genes (DEGs)

Aptamers and Antisense Oligonucleotides for Diagnosis and Treatment of Hematological Diseases.

Aptamers or chemical antibodies are single-stranded DNA or RNA oligonucleotides that bind proteins and small molecules with high affinity and specificity by recognizing tertiary or quaternary structures as antibodies. Aptamers can be easily produced in vitro through a process known as systemic evolution of ligands by exponential enrichment (SELEX) or a cell-based SELEX procedure. Aptamers and modified aptamers, such as slow, off-rate, modified aptamers (SOMAmers), can bind to target molecules with less polar and more hydrophobic interactions showing slower dissociation rates, higher stability,

The Landscape of lncRNAs in Multiple Myeloma: Implications in the "Hallmarks of Cancer", Clinical Perspectives and Therapeutic Opportunities.

Long non-coding RNAs (lncRNAs) are transcripts longer than 200 nucleotides that are not translated into proteins. Nowadays, lncRNAs are gaining importance as key regulators of gene expression and, consequently, of several biological functions in physiological and pathological conditions, including cancer. Here, we point out the role of lncRNAs in the pathogenesis of multiple myeloma (MM). We focus on their ability to regulate the biological processes identified as "hallmarks of cancer" that enable malignant cell transformation, early tumor onset and progression. The aberrant expression of lncR

Твердая неэптическая гипераммония, связанная с уреаплазмой парвума и инфекциями гомини Микопласмы в двойном иммунозапугивании женщины, представляющей как предполагаемый перитональный карциноматоз.

Острая гипераммония, не связанная с гепатической гипераммонией, является редким, но потенциально опасным для жизни заболеванием у пациентов, страдающих иммунокомпромиссной болезнью. Виды Ureaplasma и Mycoplasma являются быстродействующими врожденными организмами, которые генерируют аммиак и могут вызывать распространенную культурно-отрицательную инфекцию. Мы сообщаем о случае 63-year-old Женщина, получающая двойную биологическую терапию, оклелизумаб от множественных склерозов и секукинуумаб от псориаза, которая имела историю стерильности пюрии и симптомов мочи ниже. В течение двух месяцев ее с

Advances in Understanding Mitochondrial MicroRNAs (mitomiRs) on the Pathogenesis of Triple-Negative Breast Cancer (TNBC).

Triple-negative breast cancer (TNBC) is characterized by poor outcome and the most challenging breast cancer type to treat worldwide. TNBC manifests distinct profile of mitochondrial functions, which dictates reprogrammed metabolism, fosters tumor progression, and notably serves as therapeutic targets. Mitochondrial microRNAs (mitomiRs) are a group of microRNAs that critically modulate mitochondrial homeostasis. By a pathway-centric manner, mitomiRs tightly orchestrate metabolic reprogramming, redox status, cell apoptosis, mitochondrial dynamics, mitophagy, mitochondrial DNA (mtDNA) maintenanc

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… In this regard, Manda et al. showed that miR-499a acts to mediate the suppression of DNA polymerase beta (POLB), which plays a master role in the repair and genome stability of mtDNA [ 76 ]. We summarized the mechanisms of mitomiRs acting on mtDNA maintenance of TNBC in Figure 5 . 7. …

The Mode-of-Action of Targeted Alpha Therapy Radium-223 as an Enabler for Novel Combinations to Treat Patients with Bone Metastasis.

Bone metastasis is a common clinical complication in several cancer types, and it causes a severe reduction in quality of life as well as lowering survival time. Bone metastases proceed through a vicious self-reinforcing cycle that can be osteolytic or osteoblastic in nature. The vicious cycle is characterized by cancer cells residing in bone releasing signal molecules that promote the differentiation of osteoclasts and osteoblasts either directly or indirectly. The increased activity of osteoclasts and osteoblasts then increases bone turnover, which releases growth factors that benefit metast

RNA therapeutics in targeting G protein-coupled receptors: Recent advances and challenges.

G protein-coupled receptors (GPCRs) are the major targets of existing drugs for a plethora of human diseases and dominate the pharmaceutical market. However, over 50% of the GPCRs remain undruggable. To pursue a breakthrough and overcome this situation, there is significant clinical research for developing RNA-based drugs specifically targeting GPCRs, but none has been approved so far. RNA therapeutics represent a unique and promising approach to selectively targeting previously undruggable targets, including undruggable GPCRs. However, the development of RNA therapeutics faces significant cha

Диметил фумарат отменяет гепатоцеллюлярный карциномный рост, подавляя ось Nrf2/Bcl-xL и повышая эффективность сорафениба.

Гепатоклеточная карцинома (ГК) характеризуется плохим прогнозом и остается одной из основных причин смертности от рака во всем мире. Усовершенствованный КЦУК регулируется несколькими методами лечения первой линии, включая ингибиторы тиросина киназы (TKI) и иммунную терапию (mAb-PD-1 и mAb-VEGF). Вместе с тем эффективность лечения КЦХВ зачастую недолговечна. Недавние исследования показали, что активация траектории Nrf2-Bcl-xL способствует плохому прогнозу у группы пациентов с КЦХВ. Здесь мы обнаружили, что диметилфумарат (DMF), лекарство, используемое для лечения псориаза и множественного склер

A Review of Approaches to Potentiate the Activity of Temozolomide against Glioblastoma to Overcome Resistance.

A glioblastoma (GBM) is one of the most aggressive, infiltrative, and treatment-resistant malignancies of the central nervous system (CNS). The current standard of care for GBMs include maximally safe tumor resection, followed by concurrent adjuvant radiation treatment and chemotherapy with the DNA alkylating agent temozolomide (TMZ), which was approved by the FDA in 2005 based on a marginal increase (~2 months) in overall survival (OS) levels. This treatment approach, while initially successful in containing and treating GBM, almost invariably fails to prevent tumor recurrence. In addition to

Influence of the Mediterranean Diet on Healthy Aging.

The life expectancy of the global population has increased. Aging is a natural physiological process that poses major challenges in an increasingly long-lived and frail population. Several molecular mechanisms are involved in aging. Likewise, the gut microbiota, which is influenced by environmental factors such as diet, plays a crucial role in the modulation of these mechanisms. The Mediterranean diet, as well as the components present in it, offer some proof of this. Achieving healthy aging should be focused on the promotion of healthy lifestyle habits that reduce the development of pathologi

Molecular diagnostics in cancer patients with suspected respiratory mold infections.

Invasive fungal infections (IFIs), including aspergillosis and mucormycosis, are serious complications in cancer patients. Reliable detection of etiologic agents is challenging but important for optimal patient management. In a prospective multicenter study, we compared fungal detection by culture, specific and unspecific qPCRs, and fluorescence in situ hybridization (FISH) targeting Aspergillus and Mucorales in bronchoalveolar lavage fluid (BALF) and serum of adult cancer patients with suspected fungal pneumonia. In subgroups of patients, fungal DNA was amplified from serum. We evaluated 210

Cyclic Polypeptide D7 Protects Bone Marrow Mesenchymal Cells and Promotes Chondrogenesis during Osteonecrosis of the Femoral Head via Growth Differentiation Factor 15-Mediated Redox Signaling.

Osteonecrosis of the femoral head (ONFH) is a debilitating disease that is closely associated with the clinical application of high-dose glucocorticoids. Elevated oxidative stress contributes to the pathophysiological changes observed in ONFH. The lack of effective treatments besides surgical intervention highlights the importance of finding novel therapeutics. Our previous studies demonstrated that D7, a cyclic polypeptide, enhances the adhesion, expansion, and proliferation of bone marrow mesenchymal stem cells (BMSCs). Therefore, in this study, we investigated the therapeutic effects of D7