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New insights into CAR T-cell hematological toxicities: manifestations, mechanisms, and effective management strategies.

Chimeric antigen receptor (CAR) T-cell therapy represents a highly efficacious treatment modality demonstrated to enhance outcomes in patients afflicted with malignancies, particularly those enduring relapsed or refractory hematological malignancies. However, the escalating adoption of CAR T-cell therapy has unveiled several life-threatening toxicities, notably cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), infections, and hematological toxicities (HTs), thereby hindering the broad implementation of CAR T-cell therapy. HTs encompass a spectrum

Nanomedicine Approaches for Autophagy Modulation in Cancer Therapy.

Cancer is a daunting global health problem with a steadily rising incidence. Despite the wide arsenal of current anticancer therapies, challenges such as drug resistance, tumor heterogeneity, poor targeting, and severe side effects often lead to suboptimal efficacy and poor patient outcomes, highlighting the need for innovative therapies. Autophagy modulation has emerged as an attractive approach to complement existing therapies. The dual role of autophagy in cancer promotion and suppression has inspired the development of new drugs and therapeutic strategies focusing on both inhibition and in

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… Mannosylation enhanced NP selectivity for drug‐resistant HCT8/ADR cells overexpressing the mannose receptor, resulting in an 89% tumor inhibition rate. … The combination reversed MDR through targeted delivery to mannose receptor‐overexpressing cells, improved DOX accumulation in the nucleus, increased apoptosis, and induced autophagy due to DHA. …

Subject index

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Platycodon grandiflorum, as a medicinal and food homologous plant: a comprehensive review of anti-tumor components, mechanisms, modern applications, and preventive healthcare.

Platycodon grandiflorum (Jacq.) A. D C. (P. grandiflorum), as a medicinal and edible plant, is widely distributed in China. In terms of Chinese medical theories, Traditional Chinese Medicine (TCM) believes that the root of P. grandiflorum has the functions of relieving sore throat, eliminating phlegm, and draining pus, and is widely used in lung diseases and respiratory system disorders. Modern pharmacological studies have shown that Platycodon grandiflorum saponin, flavonoids, polysaccharides, and phenolic acids are the main active components of P. grandiflorum, which have significant antitus

Methamphetamine induces transcriptional changes in cultured HIV-infected mature monocytes that may contribute to HIV neuropathogenesis.

HIV-associated neurocognitive impairment (HIV-NCI) persists in 15-40% of people with HIV (PWH) despite effective antiretroviral therapy. HIV-NCI significantly impacts quality of life, and there is currently no effective treatment for it. The development of HIV-NCI is complex and is mediated, in part, by the entry of HIV-infected mature monocytes into the central nervous system (CNS). Once in the CNS, these cells release inflammatory mediators that lead to neuroinflammation, and subsequent neuronal damage. Infected monocytes may infect other CNS cells as well as differentiate into macrophages,

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… MRC2, a member of mannose receptor family, binds and internalizes collagen contributing to matrix degradation and turnover ( 56 ). … Mannose receptor 2 attenuates renal fibrosis. J Am Soc Nephrol (2012) 23(2):236–51. doi: 10.1681/asn.2011030310 57. Romagnoli M, Mineva ND, Polmear M, Conrad C, Srinivasan S, Loussouarn D, et al. ADAM8 expression in invasive breast cancer promotes tumor dissemination and metastasis. …

The Complosome: An Emerging Intracellular Complement Network in Cancer Development and Therapy.

The complement system is traditionally recognized as a major effector of innate immunity, essential for pathogen clearance, inflammation and the maintenance of tissue homeostasis. In recent years, however, its role in cancer has been substantially redefined. Beyond its canonical extracellular activity, complement has emerged as a multifaceted regulator of tumor biology, acting not only within the tumor microenvironment but also intracellularly through the recently described intracellular complement system (complosome). While extracellular complement primarily shapes immune responses and the tu

A Review of Gaucher Disease Pathophysiology, Clinical Presentation and Treatments.

Gaucher disease (GD, ORPHA355) is a rare, autosomal recessive genetic disorder. It is caused by a deficiency of the lysosomal enzyme, glucocerebrosidase, which leads to an accumulation of its substrate, glucosylceramide, in macrophages. In the general population, its incidence is approximately 1/40,000 to 1/60,000 births, rising to 1/800 in Ashkenazi Jews. The main cause of the cytopenia, splenomegaly, hepatomegaly, and bone lesions associated with the disease is considered to be the infiltration of the bone marrow, spleen, and liver by Gaucher cells. Type-1 Gaucher disease, which affects the

Изучение связи между 91 циркуляцией воспламенительных протеинов и нейродегенеративными заболеваниями: двухнаправленный анализ менделей и биоинформатики.

Циркуляция подстрекательских белков играет важную роль в патогенезе нейродегенеративных заболеваний (НДД). Однако точная причинно-следственная связь и механизмы, лежащие в основе их взаимодействия, по-прежнему остаются неясными. МЕТОДЫ: В каталоге GWAS были получены данные по 91 циркуляционному подстрекательскому протеину в рамках исследования ассоциации геномов (GWAS). Кроме того, данные GWAS о болезни Паркинсона (PD), болезни Альцгеймера (AD), амиотропическом боковом склерозе (ALS), множественном склерозе (MS) и ишемическом инсульте (IS) были получены в рамках проекта IEU Open GWAS. Для анал

Targeted drug approvals in 2023: breakthroughs by the FDA and NMPA.

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Metagenomic Next-Generation Sequencing Reveals Individual Composition and Dynamics of Anelloviruses during Autologous Stem Cell Transplant Recipient Management.

Over recent years, there has been increasing interest in the use of the anelloviruses, the major component of the human virome, for the prediction of post-transplant complications such as severe infections. Due to an important diversity, the comprehensive characterization of this viral family over time has been poorly studied. To overcome this challenge, we used a metagenomic next-generation sequencing (mNGS) approach with the aim of determining the individual anellovirus profile of autologous stem cell transplant (ASCT) patients. We conducted a prospective pilot study on a homogeneous patient

Bispecific antibodies and nanotechnology: a strategic alliance in cancer immunotherapy.

Bispecific antibodies (bsAbs), designed to recognize two distinct antigens or epitopes, enable innovative mechanisms of action for emerging generations of cancer immunotherapies. Despite their potential, bsAb therapeutics face several challenges related to their biodistribution and pharmacokinetics, which often result in a suboptimal efficacy/toxicity balance. Starting with a brief description of the relevance of bsAbs in cancer immunotherapy, this review aims to critically analyze the synergistic potential of nanotechnology and bsAb technology oriented to enhance therapeutic efficiency while

Dying of Stress: Chemotherapy, Radiotherapy, and Small-Molecule Inhibitors in Immunogenic Cell Death and Immunogenic Modulation.

Innovative strategies to re-establish the immune-mediated destruction of malignant cells is paramount to the success of anti-cancer therapy. Accumulating evidence suggests that radiotherapy and select chemotherapeutic drugs and small molecule inhibitors induce immunogenic cell stress on tumors that results in improved immune recognition and targeting of the malignant cells. Through immunogenic cell death, which entails the release of antigens and danger signals, and immunogenic modulation, wherein the phenotype of stressed cells is altered to become more susceptible to immune attack, radiother

Targeting Protein Degradation Pathways in Tumors: Focusing on their Role in Hematological Malignancies.

Cells must maintain their proteome homeostasis by balancing protein synthesis and degradation. This is facilitated by evolutionarily-conserved processes, including the unfolded protein response and the proteasome-based system of protein clearance, autophagy, and chaperone-mediated autophagy. In some hematological malignancies, including acute myeloid leukemia, misfolding or aggregation of the wild-type p53 tumor-suppressor renders cells unable to undergo apoptosis, even with an intact p53 DNA sequence. Moreover, blocking the proteasome pathway triggers lymphoma cell apoptosis. Extensive studie

Food and Drug Administration (FDA) Approvals of Biological Drugs in 2023.

An increase in total drug (small molecules and biologics) approvals by the Food and Drug Administration (FDA) was seen in 2023 compared with the previous year. Cancer remained the disease most targeted by monoclonal antibodies (mAbs), followed by autoimmune conditions. Our data reveal the prevalence of approvals for biologics even during years when the total number of authorizations was low, such as in 2022. Over half the drugs that received the green light in 2023 benefited from expedited programs, as the incidence of many diseases increased. In addition, over half of the biologics approved r

Molecular targets for anticancer therapies in companion animals and humans: what can we learn from each other?

Despite clinical successes in the treatment of some early stage cancers, it is undeniable that novel and innovative approaches are needed to aid in the fight against cancer. Targeted therapies offer the desirable feature of tumor specificity while sparing healthy tissues, thereby minimizing side effects. However, the success rate of translation of these therapies from the preclinical setting to the clinic is dramatically low, highlighting an important point of necessary improvement in the drug development process in the oncology field. The practice of a comparative oncology approach can addres

Microbiota-derived metabolites as modulators of cancer immunotherapy response.

The microbiome is a key regulator of host homeostasis and immune activity, in part through the production of metabolites. These microbiota-derived metabolites can modulate both the innate and adaptive immune system, as well as directly target tumour cells, thereby regulating anti-tumour immunity and response to immunotherapy. Here, we describe the current mechanistic knowledge on how these metabolites exert their effects and outline the methodologies used to detect and assess these metabolites. Finally, we summarize microbiota-targeted therapies capable of improving microbial functionality to

Osteoporosis and the Potential of Cell-Based Therapeutic Strategies.

Osteoporosis, the most common chronic metabolic bone disease, is characterized by low bone mass and increased bone fragility. Nowadays more than 200 million individuals are suffering from osteoporosis and still the number of affected people is dramatically increasing due to an aging population and longer life, representing a major public health problem. Current osteoporosis treatments are mainly designed to decrease bone resorption, presenting serious adverse effects that limit their safety for long-term use. Numerous studies with mesenchymal stem cells (MSCs) have helped to increase the knowl

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… PICP is stabilized by disulphide bonds and is cleared by liver endothelial cells via the mannose receptor which can be regulated by growth and thyroid hormones [ 89 ]. PICP presents a short serum half-life of only 6–8 minutes, which limits its use as biomarker. … Circulating C-terminal propeptide of type I procollagen is cleared mainly via the mannose receptor in liver endothelial cells Biochem. J. 1990 271 345 350 10.1042/bj2710345 2241919 PMC1149560 90. Vasikaran S. Cooper C. Eastell R. Griesmacher A. Morris H.A. Trenti T. Kanis J.A. …

Uncommon Factors Leading to Nephrotic Syndrome.

Nephrotic syndrome (NS) is characterized by proteinuria, hypoalbuminemia, edema, and hyperlipidemia. Apart from the traditional causes of NS, such as minimal change disease, focal segmental glomerulosclerosis, diabetes, infections, malignancies, autoimmune conditions, and nephrotoxic agents, there are also rare causes of NS, whose knowledge is of the utmost importance. The aim of this article was to highlight the less well-known causes that have a significant impact on diagnosis and treatment. Genetic syndromes such as Schimke immuno-osseous dysplasia, familial lecithin-cholesterol acyltransfe

Promising Experimental Treatments for Lupus Nephritis: Key Talking Points and Potential Opportunities.

Lupus nephritis (LN) is a frequent and serious complication of systemic lupus erythematosus (SLE), impairing patients' quality of life and significantly increasing mortality. Despite optimizing the use of conventional immunosuppressants and other biological drugs, its management remains unsatisfactory. This is mainly due to the heterogeneity of SLE, but also to insufficiently effective treatment regimens and clinical trial limitations (strict criteria, low number of patients included, and side effects). Most clinical trials of new biological therapies have failed to meet their primary endpoint

"Bioinspired" Membrane-Coated Nanosystems in Cancer Theranostics: A Comprehensive Review.

Achieving precise cancer theranostics necessitates the rational design of smart nanosystems that ensure high biological safety and minimize non-specific interactions with normal tissues. In this regard, "bioinspired" membrane-coated nanosystems have emerged as a promising approach, providing a versatile platform for the development of next-generation smart nanosystems. This review article presents an in-depth investigation into the potential of these nanosystems for targeted cancer theranostics, encompassing key aspects such as cell membrane sources, isolation techniques, nanoparticle core sel