Результаты поиска

Panobinostat-loaded folate targeted liposomes as a promising drug delivery system for treatment of canine B-cell lymphoma.

IntroductionCancer is a major public health problem with over 19 million cases reported in 2020. Similarly to humans, dogs are also largely affected by cancer, with non-Hodgkin's lymphoma (NHL) among the most common cancers in both species. Comparative medicine has the potential to accelerate the development of new therapeutic options in oncology by leveraging commonalities between diseases affecting both humans and animals. Within this context, in the present study, we investigated the potential of panobinostat (Pan)-loaded folate-targeted PEGylated liposomes (FA-PEG-Pan-Lip) for the treatmen

Resveratrol and clinical trials: the crossroad from in vitro studies to human evidence.

Resveratrol (3,5,4'-trihydroxy-trans-stilbene) is a non-flavonoid polyphenol that may be present in a limited number of foodstuffs such as grapes and red wine. Resveratrol has been reported to exert a plethora of health benefits through many different mechanisms of action. This versatility and presence in the human diet have drawn the worldwide attention of many research groups over the past twenty years, which has resulted in a huge output of in vitro and animal (preclinical) studies. In line with this expectation, many resveratrol- based nutraceuticals are consumed all over the world with qu

Development of an Active Chimeric IL13Rα2 ADC for Diffuse Intrinsic Pontine Glioma.

IntroductionDiffuse intrinsic pontine glioma (DIPG) is a rare pediatric brain tumor with a critical unmet need due to the lack of approved, curative interventions available. The interweaving of malignant cells with normal tissue makes surgical extraction essentially impossible, and radiation provides only transient benefit. The recent ONC201 FDA approval, however, suggests DIPG therapy is tractable. Having identified overexpression of IL13Rα2 in DIPG tumor tissue versus normal brain tissue, we investigated binding of commercially available IL13Rα2 monoclonal antibodies. The top candidate antib

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… The solvent of deruxtecan was 90% corn oil + 10% DMSO. …

Совершенствование иммунотерапии клеток ИНКТ путем интеграции оптимизированных эндодоменов ЦАР и участников ИНКТ.

Клетки ИНКТ становятся весьма перспективной платформой иммунотерапии для лечения рака. Чтобы максимально увеличить антираковую активность CAR-INKT против рака крови, мы изучили оптимальные конструкции CAR и их комбинацию с новыми специфичными участниками INKT. Мы находим, что среди пяти различных эндодомен ЦАР, подкрепляемых возросшей вспыльчивостью и перекрестным разговором между Plexin D1 на CAR-INKT и Semaphorin 4 A на клетках миэломы, BCMA CD28z CAR-INKT проявляет наибольшую активность против миэломы. В частности, CD28z CAR-INKT опережает их коллег CAR-T. В целях расширения потенциала CAR-

Activation of Kir4.1 Channels by 2-D08 Promotes Myelin Repair in Multiple Sclerosis.

Multiple sclerosis (MS) is a chronic inflammatory disease that leads to myelin loss and neurological dysfunction. Clinical studies show increased anti-Kir4.1 antibody levels in MS patients' serum, indicating its diagnostic potential. However, the specific mechanism has remained elusive. In a mouse model of experimental autoimmune encephalomyelitis (EAE), it is found that impaired Kir4.1 channels in oligodendrocyte precursor cells (OPCs) hindered myelin repair in the spinal cord. Using a thermal shift assay (TSA), the small molecule 2-D08 is identified, which effectively activated Kir4.1 channe

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… Cre recombinase induction in Pdgfrα‐creER TM ; Kir4.1 f/f mice and Pdgfrα‐creER TM ; mGFP mice were achieved via intraperitoneal injection of tamoxifen (120 mg kg −1 in corn oil) for five consecutive days. …

Cancer prevention programmes in Mexico: are we doing enough?

Cancer has increased in all the countries of the world and Mexico is no exception. The recognised risk factors for the main types of cancer are reviewed and searched through the Mexican government web pages and cancer prevention programmes to tackle the risk factors in the population. The Mexican government, a member of the World Health Organization, shows that the main approach is an early diagnosis rather than prevention, forgetting that an ounce of prevention is better than a pound of cure. Effective public programmes should be promoted to reduce preventable risk factors in the population (

Perspective Applications and Associated Challenges of Using Nanocellulose in Treating Bone-Related Diseases.

Bone serves to maintain the shape of the human body due to its hard and solid nature. A loss or weakening of bone tissues, such as in case of traumatic injury, diseases (e.g., osteosarcoma), or old age, adversely affects the individuals quality of life. Although bone has the innate ability to remodel and regenerate in case of small damage or a crack, a loss of a large volume of bone in case of a traumatic injury requires the restoration of bone function by adopting different biophysical approaches and chemotherapies as well as a surgical reconstruction. Compared to the biophysical and chemothe

PROCEEDINGS 32nd Symposium ESVN-ECVN WROCLAW, POLAND 12th-14th September 2019. Selected research communications of the 32nd Symposium of the ESVN-ECVN Wroclaw, Poland 12th to 14th September 2019.

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Exploring the Molecular Mechanisms by Which DEHP Promotes the Occurrence and Progression of Kidney Stones Based on Network Toxicology and Experimental Validation.

BACKGROUND: The global burden of kidney stones is increasing, while di(2-ethylhexyl) phthalate (DEHP), a widespread plasticizer and endocrine-disrupting pollutant, has been implicated as a potential environmental risk factor. This study investigated the mechanisms by which DEHP may aggravate calcium oxalate kidney stones through network toxicology, computational analyses, and experimental validation. METHODS: DEHP- and kidney stone-related targets were retrieved from six databases. Shared targets were analyzed using protein-protein interaction networks and Gene Ontology and Kyoto Encyclopedia

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… DEHP was dissolved in corn oil and administered by oral gavage at a volume of 8 mL/kg once daily. Mice in the normal control and model groups received an equivalent volume of vehicle. …

The Anti-Cancer Effect of Polyphenols against Breast Cancer and Cancer Stem Cells: Molecular Mechanisms.

The high incidence of breast cancer in developed and developing countries, and its correlation to cancer-related deaths, has prompted concerned scientists to discover novel alternatives to deal with this challenge. In this review, we will provide a brief overview of polyphenol structures and classifications, as well as on the carcinogenic process. The biology of breast cancer cells will also be discussed. The molecular mechanisms involved in the anti-cancer activities of numerous polyphenols, against a wide range of breast cancer cells, in vitro and in vivo, will be explained in detail. The in

Адипоцитный β-гидроксибутират обеспечивает метаболическую стойкость в множестве миеломы.

Множественная миелома (ММ) остается неизлечимым раком крови. Ожирение является известным фактором риска, но то, как адипоциты способствуют прогрессу MM, не в полной мере понятно. Здесь мы обнаруживаем метаболический перекресток между адипоцитами и клетками MM, который способствует выживанию клеток MM под глюкозой. Мы показываем, что ограничение глюкозы активирует АМПК, срывает связь HSP90-IRF4 и делает IRF4 восприимчивым к протеасомной деградации при помощи TRIM21. Парадоксально, но такой же стресс стимулирует адипоциты к производству β-гидроксибутирата (β-OHB). Клетки MM используют β-OHB при

Therapeutic Potential of Chlorogenic Acid in Chemoresistance and Chemoprotection in Cancer Treatment.

Chemotherapeutic drugs are indispensable in cancer treatment, but their effectiveness is often lessened because of non-selective toxicity to healthy tissues, which triggers inflammatory pathways that are harmful to vital organs. In addition, tumors' resistance to drugs causes failures in treatment. Chlorogenic acid (5-caffeoylquinic acid, CGA), found in plants and vegetables, is promising in anticancer mechanisms. In vitro and animal studies have indicated that CGA can overcome resistance to conventional chemotherapeutics and alleviate chemotherapy-induced toxicity by scavenging free radicals

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… The results showed that the DPPH radical scavenging activity is higher in CGA than in α-tocopherol and butylated hydroxytoluene (BHT), with values of 36.3, 32.5, and 8.9%; while the antioxidant index (in corn oil) showed the same pattern CGA > α-tocopherol > BHT, with values of 2.33, 1.93, and 1.72, …

10th Trends in Medical Mycology Held on 8 to 11 October 2021, Aberdeen, Scotland, Organized by the European Confederation of Medical Mycology (ECMM).

Plenary Sessions: [...].

ECC-4 Abstracts

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Monoclonal antibody and protein therapeutic formulations for subcutaneous delivery: high-concentration, low-volume vs. low-concentration, high-volume.

Biologic drugs are used to treat a variety of cancers and chronic diseases. While most of these treatments are administered intravenously by trained healthcare professionals, a noticeable trend has emerged favoring subcutaneous (SC) administration. SC administration of biologics poses several challenges. Biologic drugs often require higher doses for optimal efficacy, surpassing the low volume capacity of traditional SC delivery methods like autoinjectors. Consequently, high concentrations of active ingredients are needed, creating time-consuming formulation obstacles. Alternatives to tradition

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… Viscosity Preferred solution viscosity for SC injections, especially when using PFSs, is < 10 centipoise (cP) in order to minimize injection force (also called glide force). 37 This can be a challenge for high-concentration solutions. 17 For reference, at room temperature, water, milk, and corn oil …

Combinatorial targeting of cancer bone metastasis using mRNA engineered stem cells.

BACKGROUND: Bone metastases are common and devastating to cancer patients. Existing treatments do not specifically target the disease sites and are therefore ineffective and systemically toxic. Here we present a new strategy to treat bone metastasis by targeting both the cancer cells ("the seed"), and their surrounding niche ("the soil"), using stem cells engineered to home to the bone metastatic niche and to maximise local delivery of multiple therapeutic factors. METHODS: We used mesenchymal stem cells engineered using mRNA to simultaneously express P-selectin glycoprotein ligand-1 (PSGL-1)

Disorders of the Gastrointestinal System

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Melatonin-micronutrients Osteopenia Treatment Study (MOTS): a translational study assessing melatonin, strontium (citrate), vitamin D3 and vitamin K2 (MK7) on bone density, bone marker turnover and health related quality of life in postmenopausal osteopenic women following a one-year double-blind RCT and on osteoblast-osteoclast co-cultures.

This one-year double blind randomized control trial assessed the effects of nightly melatonin, strontium (citrate), vitamin D3 and vitamin K2 (MK7; MSDK) on bone mineral density (BMD) and quality of life (QOL) in postmenopausal osteopenic women (ages 49-75). Compared to placebo, MSDK treatment increased BMD in lumbar spine (4.3%) and left femoral neck (2.2%), with an upward trend for total left hip (p=0.069). MSDK increased serum P1NP levels and reduced bone turnover (CTx:P1NP). Psychometric analyses indicated that mood and sleep quality improved for the MSDK group. MSDK-exposed human mesenchy

Advances in nanomaterial-mediated CRISPR/Cas delivery: from lipid nanoparticles to vesicle-derived systems.

Gene and genome editing therapies are increasingly connected with nanomaterials, which protect and transport fragile nucleic acids and CRISPR/Cas systems through biological barriers safely and accurately. This review discusses how different nanocarriers, including lipid-based, polymeric, inorganic, and vesicle-derived systems, can improve delivery efficiency, cell targeting, endosomal escape, and intracellular movement for gene and genome editing. It summarizes findings from early clinical and preclinical studies, comparing several carrier types such as ionizable lipid nanoparticles, polymeric

Inflammatory stromal and T cells mediate human bone marrow niche remodeling in clonal hematopoiesis and myelodysplasia.

Somatic mutations in hematopoietic stem/progenitor cells (HSPCs) can lead to clonal hematopoiesis of indeterminate potential (CHIP) and progression to myelodysplastic syndromes (MDS). Using single-cell and anatomical profiling of a large cohort of human bone marrow (BM), we show that the HSPC BM niche in CHIP and MDS is undergoing inflammatory remodeling. This includes loss of CXCL12⁺ adipogenic stromal cells and the emergence of a distinct population of inflammatory mesenchymal stromal cells (iMSCs), which arise in CHIP and become more prevalent in MDS. Functional studies in primary BM HSPC-M