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Nanogel-Based Precision Bone Regeneration: Rational Design, Biological Barrier Penetration, and Osteoporotic Microenvironment Remodeling.

The pathogenesis of osteoporosis is primarily associated with impaired communication between osteoblasts and osteoclasts, leading to disrupted bone homeostasis. Conventional biomaterials mainly rely on macroscopic structural support and are limited in their ability to precisely regulate the complex bone microenvironment and overcome biological barriers. As representative soft matter nanoplatforms, nanogels possess unique viscoelastic mechanical properties and adaptive biointerfacial properties, offering new opportunities to overcome physical barriers within bone tissues. Moving beyond previous

Integrating Nature Into Oncology: Enhancing Hematological Malignancies Therapies With Natural Medicine.

Hematological malignancies are complex clonal disorders that pose a significant threat to human health. Current treatment modalities, including radiotherapy, chemotherapy, immunotherapy, and bone marrow transplantation, have demonstrated efficacy but are often limited by side effects, drug resistance, and suboptimal cure rates. Natural medicines, as key elements of complementary and alternative medicine, exhibit considerable potential in combating hematological cancers. Particularly when used in combination with conventional therapies, they can enhance treatment efficacy and reverse drug resis

Targeting Cancer Through Thymoquinone: From Molecular Mechanisms to Clinical Prospects.

Thymoquinone (TQ), the active compound in Nigella sativa (black seed), has shown promising effects against cancer in many laboratory studies. In this review, we explore how TQ works on different aspects of cancer, from stopping cancer cell growth and spread, to triggering cancer cell death, reducing inflammation, and helping the immune system fight back. We also highlight how TQ may overcome one of the biggest problems in cancer treatment-chemoresistance. When used together with common treatments like chemotherapy, radiation, or immunotherapy, TQ has been shown to improve their effects and red

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… A study by Pang et al. demonstrated that TQ binds to the catalytic domain of DNMT1, where it competes with the methyl donor S-adenosylmethionine (SAM), or its by-product SAH (S-adenosylhomocysteine), thereby inhibiting enzymatic activity in a dose-dependent manner, with an IC 50 of approximately 30 nM …

Талидомид взаимодействует с воспалением в идиопатическом фиброзе легких.

" Трагедия Талидомида " является важной вехой в истории фармацевтической промышленности. Несмотря на ограниченные клинические испытания, прилагаются постоянные усилия по изучению Талидомида в качестве лекарства от рака и подстрекательских заболеваний, таких, как ревматуидный артрит, проказа, и COVID-19. В рамках этого обзора основное внимание уделяется возможностям борьбы с воспалением путем повторного использования талидомида для лечения идиопатического фиброза легких (ИПФ). Статьи были найдены в базе данных Scopus, сортированы и рассмотрены отдельные статьи. Содержание включает в с

Amino acid metabolism in primary bone sarcomas.

Primary bone sarcomas, including osteosarcoma (OS) and Ewing sarcoma (ES), are aggressive tumors with peak incidence in childhood and adolescence. The intense standard treatment for these patients consists of combined surgery and/or radiation and maximal doses of chemotherapy; a regimen that has not seen improvement in decades. Like other tumor types, ES and OS are characterized by dysregulated cellular metabolism and a rewiring of metabolic pathways to support the biosynthetic demands of malignant growth. Not only are cancer cells characterized by Warburg metabolism, or aerobic glycolysis, bu

Predictive and Prognostic Biomarkers for Lung Cancer Bone Metastasis and Their Therapeutic Value.

Lung cancer is the leading cause of cancer-related death worldwide. Bone metastasis, which usually accompanies severe skeletal-related events, is the most common site for tumor distant dissemination and detected in more than one-third of patients with advanced lung cancer. Biopsy and imaging play critical roles in the diagnosis of bone metastasis; however, these approaches are characterized by evident limitations. Recently, studies regarding potential biomarkers in the serum, urine, and tumor tissue, were performed to predict the bone metastases and prognosis in patients with lung cancer. In t

MicroRNAs and Glucocorticoid-Induced Apoptosis in Lymphoid Malignancies.

The initial response of lymphoid malignancies to glucocorticoids (GCs) is a critical parameter predicting successful treatment. Although being known as a strong inducer of apoptosis in lymphoid cells for almost a century, the signaling pathways regulating the susceptibility of the cells to GCs are only partly revealed. There is still a need to develop clinical tests that can predict the outcome of GC therapy. In this paper, I discuss important parameters modulating the pro-apoptotic effects of GCs, with a specific emphasis on the microRNA world comprised of small players with big impacts. The

Role of Autophagy and AMPK in Cancer Stem Cells: Therapeutic Opportunities and Obstacles in Cancer.

Cancer stem cells represent a resilient subset within the tumor microenvironment capable of differentiation, regeneration, and resistance to chemotherapeutic agents, often using dormancy as a shield. Their unique properties, including drug resistance and metastatic potential, pose challenges for effective targeting. These cells exploit certain metabolic processes for their maintenance and survival. One of these processes is autophagy, which generally helps in energy homeostasis but when hijacked by CSCs can help maintain their stemness. Thus, it is often referred as an Achilles heel in CSCs, a

Multiple Facets of Autophagy and the Emerging Role of Alkylphosphocholines as Autophagy Modulators.

Autophagy is a highly conserved multistep process and functions as passage for degrading and recycling protein aggregates and defective organelles in eukaryotic cells. Based on the nature of these materials, their size and degradation rate, four types of autophagy have been described, i.e. chaperone mediated autophagy, microautophagy, macroautophagy, and selective autophagy. One of the major regulators of this process is mTOR, which inhibits the downstream pathway of autophagy following the activation of its complex 1 (mTORC1). Alkylphosphocholine (APC) derivatives represent a novel class of a

Imiglucerase in the treatment of Gaucher disease: a history and perspective.

The scientific and therapeutic development of imiglucerase (Cerezyme(®)) by the Genzyme Corporation is a paradigm case for a critical examination of current trends in biotechnology. In this article the authors argue that contemporary interest in treatments for rare diseases by major pharmaceutical companies stems in large part from an exception among rarities: the astonishing commercial success of Cerezyme. The fortunes of the Genzyme Corporation, latterly acquired by global giant Sanofi SA, were founded on the evolution of a blockbuster therapy for a single but, as it turns out, propitious ul

Уникальные диагностические и терапевтические функции порфиринов и фтальокянинов в области фотодинамической терапии, визуализации и термостимы.

Порфиринические молекулы играют уникальную тераностическую роль в лечении болезней; они используются для отображения, обнаружения и лечения различных форм заболевших тканей, в том числе в связи с возрастной маркулярной дегенерацией и рядом различных видов рака. В настоящее время основное внимание уделяется клинической съемке опухолей; целенаправленной доставке фотосенитеров и потенциалу фотоэнцедентов в мультимодальных биомедицинских наноплатформах. В настоящем Обзоре подчеркиваются роли порфириновых молекул в области съемки и пдта, а также исследования по совершенствованию их селективного пог

Модуляторные эффекты традиционной китайской медицины и производные активных метаболитов на аутоиммунально-воспалительных путях сигнала при множестве склерозов: обзор повествования.

Множественный склероз (MS) — нервно-воспалительное заболевание с иммунной помощью, характеризующееся обезвоживанием, аксоновой травмой и обширным разрушением целостности центральной нервной системы. Экспериментальный аутоиммунный энцефаломиэлит (EAE) — наиболее часто применяемая модель для имитации патологических особенностей человека. В настоящее время еще многое предстоит сделать для совершенствования стратегии лечения MS. Все больше исследований показывают, что традиционная китайская медицина (TCM) и связанные с ней активные метаболиты полезны для лечения MS и умело регулируют уровни подстр

Precision in Action: The Role of Clustered Regularly Interspaced Short Palindromic Repeats/Cas in Gene Therapies.

Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR)-associated enzyme-CAS holds great promise for treating many uncured human diseases and illnesses by precisely correcting harmful point mutations and disrupting disease-causing genes. The recent Food and Drug Association (FDA) approval of the first CRISPR-based gene therapy for sickle cell anemia marks the beginning of a new era in gene editing. However, delivering CRISPR specifically into diseased cells in vivo is a significant challenge and an area of intense research. The identification of new CRISPR/Cas variants, particularly

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… TALENs are made from the fusion of a TALE (transcription activator-like effector) and the catalytic domain of restriction endonuclease FokI ( Table 2 ), and their engineering is also difficult. ZFNs and TALENs use engineered proteins to target specific DNA sequences in the genome. …

Unveiling the role of histone deacetylases in neurological diseases: focus on epilepsy.

Epilepsy remains a prevalent chronic neurological disease that is featured by aberrant, recurrent and hypersynchronous discharge of neurons and poses a great challenge to healthcare systems. Although several therapeutic interventions are successfully utilized for treating epilepsy, they can merely provide symptom relief but cannot exert disease-modifying effect. Therefore, it is of urgent need to explore other potential mechanism to develop a novel approach to delay the epileptic progression. Since approximately 30 years ago, histone deacetylases (HDACs), the versatile epigenetic regulators re

Mechanisms of resistance to tyrosine kinase inhibitor-targeted therapy and overcoming strategies.

Tyrosine kinase inhibitor (TKI)-targeted therapy has revolutionized cancer treatment by selectively blocking specific signaling pathways crucial for tumor growth, offering improved outcomes with fewer side effects compared with conventional chemotherapy. However, despite their initial effectiveness, resistance to TKIs remains a significant challenge in clinical practice. Understanding the mechanisms underlying TKI resistance is paramount for improving patient outcomes and developing more effective treatment strategies. In this review, we explored various mechanisms contributing to TKI resistan

Stage-specific treatment of colorectal cancer: A microRNA-nanocomposite approach.

Colorectal cancer (CRC) is among the leading causes of cancer mortality. The lifetime risk of developing CRC is about 5% in adult males and females. CRC is usually diagnosed at an advanced stage, and at this point therapy has a limited impact on cure rates and long-term survival. Novel and/or improved CRC therapeutic options are needed. The involvement of microRNAs (miRNAs) in cancer development has been reported, and their regulation in many oncogenic pathways suggests their potent tumor suppressor action. Although miRNAs provide a promising therapeutic approach for cancer, challenges such as

Molecular Mechanism of Autophagy and Its Regulation by Cannabinoids in Cancer.

Autophagy is a "self-degradation" process whereby malfunctioned cytoplasmic constituents and protein aggregates are engulfed by a vesicle called the autophagosome, and subsequently degraded by the lysosome. Autophagy plays a crucial role in sustaining protein homeostasis and can be an alternative source of energy under detrimental circumstances. Studies have demonstrated a paradoxical function for autophagy in cancer, displaying both tumour suppressive and tumour promotive roles. In early phases of tumour development autophagy promotes cancer cell death. In later phases, autophagy enables canc

The Role of Plant-Derived Natural Products as a Regulator of the Tyrosine Kinase Pathway in the Management of Lung Cancer.

One of the most common malignant tumors worldwide is lung cancer, and it is associated with the highest death rate among all cancers. Traditional treatment options for lung cancer include radiation, chemotherapy, targeted therapy, and surgical resection. However, the survival rate is low, and the outlook is still dreadfully dire. The pursuit of a paradigm change in treatment approaches is, therefore, imperative. Tyrosine kinases (TKs), a subclass of protein kinases, regulate vital cellular function by phosphorylating tyrosine residues in proteins. Mutations, overexpression, and autocrine parac

Does DPP-IV Inhibition Offer New Avenues for Therapeutic Intervention in Malignant Disease?

Dipeptidyl peptidase IV (DPP-IV, CD26) is frequently dysregulated in cancer and plays an important role in regulating multiple bioactive peptides with the potential to influence cancer progression and the recruitment of immune cells. Therefore, it represents a potential contributing factor to cancer pathogenesis and an attractive therapeutic target. Specific DPP-IV inhibitors (gliptins) are currently used in patients with type 2 diabetes mellitus to promote insulin secretion by prolonging the activity of the incretins glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypep

Targeting multiple signaling pathways: the new approach to acute myeloid leukemia therapy.

Acute myeloid leukemia (AML) is the most common form of acute leukemia in adults and the second most common form of acute leukemia in children. Despite this, very little improvement in survival rates has been achieved over the past few decades. This is partially due to the heterogeneity of AML and the need for more targeted therapeutics than the traditional cytotoxic chemotherapies that have been a mainstay in therapy for the past 50 years. In the past 20 years, research has been diversifying the approach to treating AML by investigating molecular pathways uniquely relevant to AML cell prolife