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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

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… Cobalt (III) oxide nanoparticles (Co 3 O 4 NPs) were used to deliver β-arrestin1 siRNAs into the 1321N1 cells; MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide) assay showed that Co 3 O 4 NPs were non-toxic in this cell line. 236 G protein-coupled receptor 1 (OGR1 or GPR68) mediates …

Gene editing in cancer therapy: overcoming drug resistance and enhancing precision medicine.

The CRISPR system has revolutionized cancer gene therapy, offering unparalleled precision in genetic manipulation for targeted oncogene disruption, mutation correction, and immune system modulation. This breakthrough tool has demonstrated remarkable potential in overcoming drug resistance, enhancing chemotherapy sensitivity, and improving immunotherapy strategies such as CRISPR-engineered CAR-T cells. Additionally, oncolytic virus-mediated CRISPR delivery has emerged as a novel approach for tumor-specific gene editing, minimizing off-target effects. The rapid transition of CRISPR-based cancer

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… S262: The cobalt-lym Study Of Ctx130: a phase 1 dose escalation study Of Cd70-targeted allogeneic crispr-Cas9–engineered Car T cells in patients with relapsed/refractory (R/R) T-cell malignancies. HemaSphere. 2022;6:163–4. 57. Hu Y, Zhou Y, Zhang M, Ge W, Li Y, Yang L, et al. …

Гомоцитистейн, питание и Гут Микробиота: всеобъемлющий обзор текущих данных и понимания.

Гомоциштейн, содержащий серную аминокислоту, является промежуточным продуктом во время метаболизма метатонина, жизненно важной аминокислоты. Возвышенная концентрация гомоцистайна в плазме, названной гипергомоцистистемией, в значительной степени связана с возникновением нескольких заболеваний, включая диабет, множественный склероз, остеопороз, рак и нейродегенеративные расстройства, такие как слабоумие, болезни Альцгеймера и Паркинсона. Сообщалось о взаимодействии между метаболическими путями гомоциштейна и кишечной микробиотой, а также о конкретных микробных сигнатурах у лиц, страдающих гиперг

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… Vitamin B12, also known as cobalamin, is a cobalt-based nutrient produced by bacteria, crucial for mammals, who obtain it through their diet. Its absorption and distribution involve intricate biological mechanisms, including specific proteins, receptors, and transporters. …

MicroRNAs in Aseptic Loosening of Prosthesis: Pathophysiology and Potential Therapeutic Approaches.

OBJECTIVES: Aseptic loosening (AL) is one of the leading causes of total joint arthroplasty (TJA) revision. Discovering the roles of microRNAs (miRNA/miR) in ontogenesis and osteolysis has attracted more attention to diagnosing and treating bone disorders. This review aimed to summarize miRNA biogenesis and describe the involvement of miRNAs in AL of implants. METHODS: A detailed search was carried out on scientific search engines, including Google Scholar, Web of Science, and PubMed, to find appropriate papers related to subjects. The search process was performed using the following keywords

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… Myo18a, which closely participates in suppressing inflammatory responses of macrophages via pathway regulating CD14 trafficking. 42 In another study, miR-130b was reported to participate in PPO via reducing the gene expression of frizzled-related protein (FRZB) in mice model induced by implantation of cobalt-chromium-molybdenum …

Testing mapping algorithms of the cancer-specific EORTC QLQ-C30 onto EQ-5D in malignant mesothelioma.

BackgroundIn order to estimate utilities for cancer studies where the EQ-5D was not used, the EORTC QLQ-C30 can be used to estimate EQ-5D using existing mapping algorithms. Several mapping algorithms exist for this transformation, however, algorithms tend to lose accuracy in patients in poor health states. The aim of this study was to test all existing mapping algorithms of QLQ-C30 onto EQ-5D, in a dataset of patients with malignant pleural mesothelioma, an invariably fatal malignancy where no previous mapping estimation has been published.MethodsHealth related quality of life (HRQoL) data whe

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… The data was obtained from the South West Area Mesothelioma and Permetrexed Trial (SWAMP Trial) which was a charity funded (Cobalt Appeal Fund Registered Charity Number 1090790) trial of chemotherapy in mesothelioma. References 1. NICE. Guide to the methods of technology appraisal. …

The inhibition of RANKL-induced osteoclastogenesis through the suppression of p38 signaling pathway by naringenin and attenuation of titanium-particle-induced osteolysis.

The aim of this study was to assess the effect of naringenin on osteoclastogenesis and titanium particle-induced osteolysis. Osteolysis from wear-induced particles and aseptic loosening are the most frequent late complications of total joint arthroplasty leading to revision of the prosthesis. Osteolysis during aseptic loosening is most likely due to increased bone resorption by osteoclasts. Through in vitro studies, we demonstrated that naringenin, a naturally occurring flavanone in grapefruit and tomatoes, exerts potent inhibitory effects on the ligand of the receptor activator of nuclear fac

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… Expression of inflammatory cytokines, RANKL and OPG induced by titanium, cobalt-chromium and polyethylene particles. Biomaterials. 2005;26:1695–1702. doi: 10.1016/j.biomaterials.2004.05.017. 54. Baumann B., Rader C.P., Seufert J., Noth U., Rolf O., Eulert J., Jakob F. …

Essential Medicinal Chemistry of Essential Medicines.

Since 1977, the World Health Organization publishes a list of essential medicines, i.e., those that satisfy the priority health care needs of the population and are selected with regard to disease prevalence and public health relevance, evidence of clinical efficacy, and safety, as well as comparative costs and cost-effectiveness. The Essential Medicines List (EML) is an invaluable tool for all countries to select those medicines that have an excellent risk/benefit ratio and that are reputed to be of pivotal importance to health. In the present perspective, we describe the chemical composition

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… The remaining elements are arsenic in melarsoprol, antimonium in sodium stibogluconate, cobalt in hydroxocobalamin, and iron in sodium nitroprusside. Which Are the Most Represented Functional Groups and Heterocycles in the EML? …

Patient reported change in pain outcome among stage IV cancer patients with bone metastases following palliative radiotherapy: A prospective study from Ethiopia.

BackgroundCancer is reported to be on the rise in low-income countries where most patients present in either locally advanced or metastatic stage of the disease. The standard treatment for cancer patients with metastatic bone disease includes radiotherapy, systemic agents and surgical intervention. Most cancer patients in Ethiopia present in advanced stage of the disease. Among these patients with advanced cancer are those with painful metastasis to the bone. Most commonly these patients are offered palliative single fraction 8 gy or fractionated 20 gy of radiotherapy to painful bone metastase

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… There are five clinical oncologists, one functional cobalt teletherapy machine and one high dose brachytherapy for 110 million Ethiopian populations. …

Effect of N-Acetylcysteine on Cisplatin Toxicity: A Review of the Literature.

N-acetylcysteine (NAC) is a membrane-permeable cysteine precursor capable of enhancing the intracellular cysteine pool, enhancing cellular glutathione (GSH) synthesis, and thus potentiating the endogenous antioxidant mechanism. Late administration of NAC after cisplatin has been shown in different in vivo studies to reduce the side effects caused by various toxicities at different levels without affecting the antitumor efficacy of platinum, improving total and enzymatic antioxidant capacity and decreasing oxidative stress markers. These characteristics provide NAC with a rationale as a potenti

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… Role of direct reactivity with metals in chemoprotection by N-acetylcysteine against chromium (VI), cadmium (II), and cobalt (II). Free Radic Biol Med . 2013;65:262–269. doi: 10.1016/j.freeradbiomed.2013.06.028 57. Higashi T, Elmeligy E, Mai Y, et al. …

Management of single brain metastasis: a practice guideline.

QUESTIONS: Should patients with confirmed single brain metastasis undergo surgical resection? Should patients with single brain metastasis undergoing surgical resection receive adjuvant whole-brain radiation therapy (wbrt)? What is the role of stereotactic radiosurgery (srs) in the management of patients with single brain metastasis? PERSPECTIVES: Approximately 15%-30% of patients with cancer will develop cerebral metastases over the course of their disease. Patients identified as having single brain metastasis generally undergo more aggressive treatment than do those with multiple metastases

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… Radiosurgery for solitary brain metastases using the cobalt-60 gamma unit: methods and results in 24 patients. Int J Radiat Oncol Biol Phys. 1991;20:1287–95. doi: 10.1016/0360-3016(91)90240-5. 13. Sturm V, Kimmig B, Engenhardt R, et al. Radiosurgical treatment of cerebral metastases. …

Sohlh2 inhibited the angiogenesis of hepatocellular carcinoma through the HIF-1α/VEGFA pathway.

PurposeTo investigate the role of Sohlh2 in hepatocellular carcinoma (HCC) and its potential mechanisms.MethodsThis study focused on Hep3B and HepG2 cells and employed lentiviral transfection to create Sohlh2 overexpression and knockdown models. Through CCK8, flow cytometry, angiogenesis and immunofluorescence experiments, the effects of Sohlh2 on tumor cell proliferation, cell cycle progression, apoptosis, and angiogenesis were investigated. Additionally, its regulatory role in the HIF-1α/VEGFA pathway was explored. The experiments were repeated after introducing the Sohlh2 agonist CoCl2 and

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… Cobalt chloride induced apoptosis by inhibiting GPC3 expression via the HIF-1α/c-Myc axis in HepG2 cells. Onco. Targets Ther. 2019;12:10663–10670. doi: 10.2147/OTT.S227215. 24. Xu H., Chen Y., Li Z., Zhang H., Liu J., Han J. …

Update on current pancreatic treatments: from molecular pathways to treatment.

Pancreatic cancer is still diagnosed at a late stage although we have novel diagnostic tools. Pancreatic cancer chemotherapy treatment resistance is observed and therefore novel treatments are in need. Anti-cancer stem cell therapy, combination of chemotherapy and/or radiotherapy with immunotherapy, proteins/enzymes and gene therapy are currently under evaluation. Targeted treatment with tyrosine kinase inhibitors is also administered and novel inhibitors are also under evaluation. In the current review we present recent data from our search within the year 2018.

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… Porphyrins: Porphyrin-1(Cobalt containing) and Porphyrin-2 (Palladium containing) are observed to have high affinity towards K-ras-promoter/G-quadruplex. These porphyrins exhibited significant cytotoxicity in human pancreatic ductal carcinoma cell line PANC-1 and MiaPaCa2 and blocked metastasis. …

Exploring the Therapeutic Potential of Ganoderma lucidum in Cancer.

Triterpenoids, such as ganoderic acid, and polysaccharides, including β-D-glucans, α-D-glucans, and α-D-mannans, are the main secondary metabolites of the medicinal fungus Ganoderma lucidum. There is evidence of the effects of ganoderic acid in hematological malignancies, whose mechanisms involve the stimulation of immune response, the macrophage-like differentiation, the activation of MAP-K pathway, an IL3-dependent cytotoxic action, the induction of cytoprotective autophagy, and the induction of apoptosis. In fact, this compound has been tested in twenty-six different human cancer cell types

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… Additionally, a number of minerals have been isolated from G. lucidum , including sodium, potassium, calcium, phosphorus, magnesium, selenium, iron, carbon, zinc, copper, manganese, chromium, arsenic, silicon, aluminum, nickel, lead, cobalt, molybdenum, and fluoride [ 11 , 60 ]. …

Advancing gene editing therapeutics: Clinical trials and innovative delivery systems across diverse diseases.

Gene editing is a groundbreaking therapeutic approach that can potentially treat a broad spectrum of genetic and acquired diseases. This review highlights recent clinical trials employing advanced gene editing technologies such as CRISPR-Cas9, zinc-finger nucleases (ZFNs), and base editors across multiple disease areas including metabolic disorders, autoimmune diseases, muscular dystrophies, and inherited eye disorders. Central to the success of these therapies is the development of efficient and safe delivery systems, including lipid nanoparticles (LNPs), viral vectors (adenoviral and lentivi

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… Methods: Staphylococcus aureus and Pseudomonas aeruginosa biofilms were grown to maturity in bioreactors according to established laboratory protocol on titanium, cobalt chromium, and polyetherketone (PEEK). … Results: Staphylococcus aureus and Pseudomonas aeruginosa biofilms were grown for 7 days on double-sided titanium, cobalt chromium, and PEEK (n = 4 each). There appeared to be a visible dose-dependent relationship based on the staining and dye concentration. …

Natural extract-derived compounds for the treatment of hematological diseases through modulation of the bone marrow microenvironment.

The bone marrow microenvironment comprises a complex network of hematopoietic stem cells, immune cells, stromal cells, and non-cellular components such as the extracellular matrix and soluble factors, collectively maintaining the homeostasis of hematopoietic stem and progenitor cells. It is highly vulnerable to pathological perturbations induced by hematologic malignancies, solid tumors, inflammatory stress, and therapeutic exposure, which collectively destabilize microenvironmental homeostasis and promote hematopoietic failure, malignant progression, and immune dysregulation. Natural products

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… For example, fisetin is a natural tetrahydroxyflavone that significantly enhances hematopoietic function in mice exposed to cobalt-60 gamma radiation. This compound promotes the recovery of hematopoietic stem and progenitor cells. It also supports the repair of the BME. …

Advancing CRISPR genome editing into gene therapy clinical trials: progress and future prospects.

Genome editing has recently evolved from a theoretical concept to a powerful and versatile set of tools. The discovery and implementation of CRISPR-Cas9 technology have propelled the field further into a new era. This RNA-guided system allows for specific modification of target genes, offering high accuracy and efficiency. Encouraging results are being announced in clinical trials employed in conditions like sickle cell disease (SCD) and transfusion-dependent beta-thalassaemia (TDT). The path finally led the way to the recent FDA approval of the first gene therapy drug utilising the CRISPR/Cas

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… CTX130 was tested in relapsed/refractory T- or B-cell malignancies under the COBALT-LYM trial and relapsed/refractory renal cell carcinoma under the COBALT-RCC trial. The drug received FDA Orphan Drug and Regenerative Medicine Advanced Therapy (RMAT) designations. …

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Targeted Drug Delivery and Theranostic Strategies in Malignant Lymphomas.

Malignant lymphomas represent the most common type of hematologic malignancies. The first clinically approved TDD modalities in lymphoma patients were anti-CD20 radioimmunoconjugates (RIT) 131I-tositumomab and 90Y-ibritumomab-tiuxetan. The later clinical success of the first approved antibody-drug conjugate (ADC) for the treatment of lymphomas, anti-CD30 brentuximab vedotin, paved the path for the preclinical development and clinical testing of several other ADCs, including polatuzumab vedotin and loncastuximab tesirine. Other modalities of TDD are based on new formulations of "old" cytostatic

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… Magnetic Nanoparticles Magnetic nanoparticles are based on ferromagnetic or ferrimagnetic metals, most commonly iron but also cobalt, nickel, and their compounds and oxides. These nanoparticles exhibit superparamagnetism. …

The Potential of Chronotherapy and Nanotherapy-Based Strategies for Glioblastoma Treatment.

Glioblastoma is the most common and aggressive brain tumour in adults, and despite ongoing efforts, effective treatment remains limited. Standard therapies often face challenges because of the tumour's specific biology, its aggressive nature, and the presence of certain physiological barriers in the brain that impede chemotherapeutics from reaching their target. Emerging research in circadian biology highlights the role of the internal circadian clock in tumour progression and treatment response. Evidence suggests that aligning therapy to patients' chronotypes could potentially improve treatme

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… Cobalt-doped iron oxide nanoparticles, stabilised with a carboxymethylcellulose capping ligand (Co-MION), induced apoptosis and ferroptosis in a 2D U87 brain culture and reduced tumour development and volume in 3D spheroids [ 107 ]. …