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Progress on new drug treatments for hepatic echinococcosis.

Echinococcosis: is a zoonotic parasitic disease caused by infection with the larvae of Echinococcus tapeworms. At present, the standardized treatment regimen for this disease consists of radical lesion resection combined with albendazole. For patients who are inoperable or experience postoperative recurrence, the treatment with anti-echinococcosis drugs is particularly crucial. To date, albendazole remains the primary drug clinically used for anti-echinococcosis treatment. However, it has inherent drawbacks such as low bioavailability, poor solubility, long treatment course, and multiple adver

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… The Proteolysis Targeting Chimeras (PROTAC) molecular technology developed by Wu and Hu (2024) endows the nano-sustained release system with dynamic regulation capabilities. …

NDP52 и его новая роль в патогенезе.

Автофагика - это процесс, способствующий выживанию, который регулирует деградацию и обновление клеточных компонентов, что делает его важнейшим механизмом для клеточного гомеостазиза. Существуют выборочные формы автофагии, характерные для ряда субстратов, таких, как патогены (бактерии или вирусы), белковые агрегаты или излишние/поврежденные органеллы. Эти процессы включают в себя в качестве ключевых игроков автофагичные рецепторы, которые связывают груз, подлежащий деградации, с автофагическим оборудованием. Среди них NDP52 (известный также как КАКПО2) был охарактеризован как «бридж» между авто

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… In addition, previous research evidence has shown promising outcomes of a proteolysis targeting chimera (PROTAC) drug. The latter is a novel small molecule named C004019 designed to simultaneously recruit E3 ligase (Vhl), and selectively enhance Tau ubiquitination, and its subsequent proteolysis. …

Metronomic chemotherapy: changing the paradigm that more is better.

The introduction of the "maximum tolerated dose" in usual treatment protocols (and its concomitant overt toxicity) made necessary the imposition of rest periods between cycles of therapy-a practice that not only involves re-growth of tumour cells, but also growth of selected clones resistant to the therapy. To avoid the problems caused by traditional chemotherapeutic regimens, a new modality of drug administration called "metronomic chemotherapy" has been proposed. This name makes reference to the chronic, equally spaced administration of (generally) low doses of various chemotherapeutic drugs

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… Antiangiogenic therapy of established tumors in human skin/severe combined immunodeficiency mouse chimeras by anti-endoglin (CD105) monoclonal antibodies, and synergy between anti-endoglin antibody and cyclophosphamide. Cancer Res. 2001;61:7846–54. 17. …

Advancements in antibody-drug conjugates as cancer therapeutics.

Antibody-drug conjugates (ADCs) represent a promising approach in targeted cancer therapy, combining the targeted precision of antibodies with the potency of cytotoxic payloads to selectively target tumour cell whilst minimising off-target effects. This review provides a comprehensive analysis of ADCs, encompassing their structural components, mechanisms of action, and clinical applications. It also examines recent technological advancements, particularly in antibody engineering and linker design, aimed at enhancing therapeutic efficacy and safety. The current clinical landscape is outlined, h

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… PLAUR domain containing 3; MEK, mitogen-activated protein extracellular signal-regulated kinase; NAD, nicotinamide adenine dinucleotide; NAMPT, nicotinamide phosphoribosyltransferase; NOD-SCID, nonobese diabetic/severe combined immunodeficiency mice; NIR, near-infrared; PROTAC, proteolysis-targeting chimeras … Proteolysis-targeting chimeras (PROTACs) in cancer therapy: present and future. Molecules. 2022;27(24):8828. doi: 10.3390/molecules27248828. 73. Maneiro M., Forte N., Shchepinova M.M., et al. Antibody–PROTAC conjugates enable HER2-dependent targeted protein degradation of BRD4. …

An Overview of Polymeric Nanoparticles-Based Drug Delivery System in Cancer Treatment.

Cancer is recognized as one of the world's deadliest diseases, with more than 10 million new cases each year. Over the past 2 decades, several studies have been performed on cancer to pursue solutions for effective treatment. One of the vital benefits of utilizing nanoparticles (NPs) in cancer treatment is their high adaptability for modification and amalgamation of different physicochemical properties to boost their anti-cancer activity. Various nanomaterials have been designed as nanocarriers attributing nontoxic and biocompatible drug delivery systems with improved bioactivity. The present

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… . | UCSF Chimera | The integrated visualization and analysis of molecular structures and related nonstructural biological data are made possible by web-based computing resources. | www.cgl.ucsf.edu > chimera 9. | VMD | The molecular visualization program displays animate and analyzes large biomolecular …

Modulating glycosphingolipid metabolism and autophagy improves outcomes in pre-clinical models of myeloma bone disease.

Patients with multiple myeloma, an incurable malignancy of plasma cells, frequently develop osteolytic bone lesions that severely impact quality of life and clinical outcomes. Eliglustat, a U.S. Food and Drug Administration-approved glucosylceramide synthase inhibitor, reduced osteoclast-driven bone loss in preclinical in vivo models of myeloma. In combination with zoledronic acid, a bisphosphonate that treats myeloma bone disease, eliglustat provided further protection from bone loss. Autophagic degradation of TRAF3, a key step for osteoclast differentiation, was inhibited by eliglustat as ev

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… Chimera blood lineages analysis BM chimera was conducted on 11 Gy lethally irradiated 8-week-old female CD45.1 + B6.SJL mice using BM cells from CD45.2 OC-specific deletion of traf3 female mice or their littermates. …

Glutathione Transferase P1-1 an Enzyme Useful in Biomedicine and as Biomarker in Clinical Practice and in Environmental Pollution.

Glutathione transferase P1-1 (GSTP1-1) is expressed in some human tissues and is abundant in mammalian erythrocytes (here termed e-GST). This enzyme is able to detoxify the cell from endogenous and exogenous toxic compounds by using glutathione (GSH) or by acting as a ligandin. This review collects studies that propose GSTP1-1 as a useful biomarker in different fields of application. The most relevant studies are focused on GSTP1-1 as a biosensor to detect blood toxicity in patients affected by kidney diseases. In fact, this detoxifying enzyme is over-expressed in erythrocytes when unusual amo

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… Three-dimensional structures of glutathione Transferases were drawn by the means of UCSF Chimera software v1.6 [ 35 ]. Chemical structures were designed by the software ChemDraw Ultra v8 (PerkinElmer Informatics, Cambridge, MA, USA). 3. … UCSF Chimera—A visualization system for exploratory research and analysis J. Comput. Chem. 2004 25 1605 1612 10.1002/jcc.20084 15264254 36. Galli F. Rovidati S. Benedetti S. Buoncristiani U. Covarelli C. Floridi A. Canestrari F. …

Tumor Biology Hides Novel Therapeutic Approaches to Diffuse Large B-Cell Lymphoma: A Narrative Review.

Diffuse large B-cell lymphoma (DLBCL) is a malignancy of immense biological and clinical heterogeneity. Based on the transcriptomic or genomic approach, several different classification schemes have evolved over the years to subdivide DLBCL into clinically (prognostically) relevant subsets, but each leaves unclassified samples. Herein, we outline the DLBCL tumor biology behind the actual and potential drug targets and address the challenges and drawbacks coupled with their (potential) use. Therapeutic modalities are discussed, including small-molecule inhibitors, naked antibodies, antibody-dru

Состояние питания, способность к антиоксидантам в рационе питания и разнообразие рациона питания у пациентов с недавно диагностированными гематологическими отклонениями: тематическое исследование.

ППОЗ: Состояние питания и способность к антиоксидантам в рационе питания являются важными факторами, определяющими клиническую устойчивость к раку; однако данные о гематологических заболеваниях по-прежнему ограничены. Мы поставили перед собой цель сравнить состояние питания, общий потенциал рациона питания с антиоксидантами (DTAC) и разнообразие рациона питания между пациентами с недавно диагностированными гематологическими отклонениями и здоровыми средствами контроля. МЕТОДЫ: Это тематическое исследование включало 34 больные с недавно диагностированными гематологическими заболеваниями12 лимфо

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… Huybrechts I, Chimera B, Hanley-Cook GT, Biessy C, Deschasaux-Tanguy M, Touvier M et al (2024) Food biodiversity and gastrointestinal cancer risk in nine European countries: analysis within a prospective cohort study. Eur J Cancer. 10.1016/j.ejca.2024.114258 15. …

MAIT Cells in the Bone Marrow of Patients with Aplastic Anemia.

Mucosal-associated invariant T cells (MAIT cells) are a subset of T cells with innate, effector-like properties that play an essential role in the immune response to microbial infections. In humans, MAIT cells are detectable in the blood, liver, and lungs, but little is known about the frequency of these cells in the bone marrow. Also, the pathogenic role, if any, of MAIT cells in the development of aplastic anemia, a disease with an exquisite origin in the bone marrow, is currently unknown. We investigated the frequency and clinical relevance of bone marrow MAIT cells in a cohort of 14 patien

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… Assessing Immune Response via NKG2D/MICA Interaction on MAIT Cells Recombinant MICA/Fc chimera (rMICA), a ligand of NKG2D, was purchased from R&D Systems (#1300-MA-050) and diluted to a concentration of 1 µg/mL in sterile PBS, and 1 mL of the solution was added to each well of a 24-well plate. …

Improved intensive care unit survival for critically ill allogeneic haematopoietic stem cell transplant recipients following reduced intensity conditioning.

The use of allogeneic haematopoietic stem cell transplantation (Allo-HSCT) is a standard treatment option for many patients with haematological malignancies. Historically, patients requiring intensive care unit (ICU) admission for transplant-related toxicities have fared extremely poorly, with high ICU mortality rates. Little is known about the impact of reduced intensity Allo-HSCT conditioning regimens in older patients on the ICU and subsequent long-term outcomes. A retrospective analysis of data collected from 164 consecutive Allo-HSCT recipients admitted to ICU for a total of 213 admission

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… by bone marrow transplant patients Critical Care Medicine 1998 26 66 70 9428545 10.1097/00003246-199801000-00018 Peggs KS Kayani I Edwards N Kottaridis P Goldstone AH Linch DC Hough R Morris EC Fielding A Chakraverty R Thomson KJ Mackinnon S Donor lymphocyte infusions modulate relapse risk in mixed chimeras …

Exploration of Site-Specific Drug Targeting-A Review on EPR-, Stimuli-, Chemical-, and Receptor-Based Approaches as Potential Drug Targeting Methods in Cancer Treatment.

Cancer has been one of the most dominant causes of mortality globally over the last few decades. In cancer treatment, the selective targeting of tumor cells is indispensable, making it a better replacement for conventional chemotherapies by diminishing their adverse side effects. While designing a drug to be delivered selectively in the target organ, the drug development scientists should focus on various factors such as the type of cancer they are dealing with according to which drug, targeting moieties, and pharmaceutical carriers should be targeted. All published articles have been collecte

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… A powerful combination approach of chemical targeting that has shown to increase the lifespan of tumor-bearing mice by 40-60% compared to control involves the use of a molecular chimera attached with a regulatory DNA sequence of transcription which can selectively be stimulated in mammalian cells and … The chimera was anchored with a prodrug form of methotrexate and 5-fluorouracil, which gets converted to its active state after the DNA coding region and β -lactamase are expressed at the target site [ 15 ]. …

CAR-Based Cell Therapy in Head and Neck Cancer: A Comprehensive Review on Clinical Applicability.

Background/Objectives: Chimeric antigen receptor T-cell (CAR-T) therapy is a novel form of adoptive cellular immunotherapy that involves modifying autologous T cells to recognize and target tumor-associated antigens (TAAs) on malignant cells, independent of major histocompatibility complex (MHC) restriction. Although CAR-T therapy has shown remarkable success in treating hematologic malignancies, its efficacy in solid tumors remains limited, largely due to the lack of tumor-specific antigens and the complexity of the tumor microenvironment. This review aims to explore the rationale for continu

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… The authors developed a CAR named T1E28z in which the promiscuous ErbB ligand T1E (a chimera derived from Transforming Growth Factor α and EGFR) is fused to a spacer domain and an intracellular domain composed of CD28 and CD3 [ 45 ]. …

Aptamer: A potential oligonucleotide nanomedicine in the diagnosis and treatment of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is one of the most common cancers with a high mortality rate. Late diagnosis and poor prognosis are still a major drawback since curative therapies such as liver resection and liver transplantation are effective only for an early stage HCC. Development of novel molecular targeting therapies against HCC may provide new options that will improve the efficiency of the diagnosis and the success of the therapy, thus ameliorating the life expectancy of the patients. The aptamer is an oligonucleotide nanomedicine that has high binding affinity and specificity to small a

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… Systemic administration of optimized aptamer-siRNA chimeras promotes regression of PSMA-expressing tumors. Nat Biotechnol. 2009;27:839–49. doi: 10.1038/nbt.1560. https://doi.org/10.1038/nbt.1560 . 88. Meek KN, Rangel AE, Heemstra JM. …

Targeting mutant p53 in cancer: from mechanistic insights to therapeutic strategies.

The tumor suppressor p53, often referred to as the “guardian of the genome,” is mutated in more than half of human cancers. These mutations have a significant impact on cancer biology and response to therapy. p53 mutations involve a range of changes that interfere with DNA binding, eliminate tumor suppressor functions, and, in many cases, confer dominant-negative or gain-of-function characteristics that actively promote oncogenesis. These mutations are closely linked to poor clinical outcomes and resistance to standard treatments. This review examines the impact of p53 mutations on cancer ther

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… (c) Proteolysis-targeting chimeras (PROTACs) are groundbreaking bifunctional small molecules designed to induce the targeted degradation of specific proteins [ 167 ]. …

Epigenetics-targeted drugs: current paradigms and future challenges.

Epigenetics governs a chromatin state regulatory system through five key mechanisms: DNA modification, histone modification, RNA modification, chromatin remodeling, and non-coding RNA regulation. These mechanisms and their associated enzymes convey genetic information independently of DNA base sequences, playing essential roles in organismal development and homeostasis. Conversely, disruptions in epigenetic landscapes critically influence the pathogenesis of various human diseases. This understanding has laid a robust theoretical groundwork for developing drugs that target epigenetics-modifyin

The progress and perspective of nanomedicine in modulating the tumor immune microenvironment.

The widespread application of nanomedicine in oncology is reshaping cancer treatment paradigms. Using the precise targeting mechanisms and the rapid advancements in nanoscale materials, nanomedicine is driving progress in cancer therapy, particularly within the complex landscape of the tumor immune microenvironment (TIM). This review provides a comprehensive overview of recent studies elucidating the critical role of nanomedicine in modulating the TIM, augmenting the efficacy of immunotherapies, and overcoming therapeutic resistance. Emphasis is placed on the significance of targeted drug deli

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… Aptamer-peptide chimeras, such as AptCD28-P60, have been developed to improve the precision targeting of Tregs, enabling a decrease in the required dosage while simultaneously amplifying the immune response 115 . …

Revealing G4 Structures as Drug Targets: Exploring the Potential of Novel Therapeutic Agents.

G-quadruplex (G4) structures represent noncanonical secondary formations found in DNA and RNA. Recent research reveals that G4s are abnormally enriched in various cancers, with closely linked to malignancy, metastatic potential, and prognosis. These structures have emerged as promising biomarkers for cancer with notable clinical relevance. Concurrently, investigations into compounds that selectively recognize DNA or RNA G4s as potential anticancer agents offer new avenues for early cancer diagnosis and therapeutic strategies. This review systematically analyzes the chemical structural characte

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… A notable breakthrough is the inducible ribonuclease targeting chimera (RIBOTAC) strategy developed by Zhang et al. [ 152 ], which conjugates an rG4 binder with a caged ribonuclease recruiter. …

Unlocking the potential of tumor-targeting peptides in precision oncology.

Targeted cancer therapy has emerged as a promising alternative to conventional chemotherapy, which is often plagued by poor selectivity, off-target effects, and drug resistance. Among the various targeting agents in development, peptides stand out for their unique advantages, including minimal immunogenicity, high tissue penetration, and ease of modification. Their small size, specificity, and flexibility allow them to target cancer cells while minimizing damage to healthy tissue selectively. Peptide-based therapies have shown great potential in enhancing the efficacy of drug delivery, improvi

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… Chimera [ 191 ], while primarily a visualization tool, integrates docking capabilities through plugins like AutoDock Vina, allowing researchers to study binding poses and interaction patterns in detail [ 192 ]. …

Механистические знания о перекрестке нейроглии в нейродегенеративных заболеваниях.

Нейродегенеративные заболевания, такие, как болезнь Альцгеймера (AD), болезнь Паркинсона (PD), Множественный Склероз (MS) и болезнь Хантингтона (HD), хотя и отличаются по своим клиническим проявлениям, имеют общую отличительную черту: нарушенная нейро-воспалительная среда, вызванная дисрегулированием нейроглиальной межклеточной связи. Нейроглиальный перекресток физиологически обеспечивается внеклеточными посредниками и деятельностью коннексинов (Cxs), формирующими белки пятен соединений пятен (Gjs) и гемиханнелей (HC), которые поддерживают внутриклеточный и внеклеточный гомеостаз. Однако накоп

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… In addition, mHTT human glial chimeras show an impaired astrocyte differentiation, confirming that defects in glial differentiation could be related to HD pathogenesis and symptoms ( Osipovitch et al., 2019 ). …