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Homocysteine and Multiple Health Outcomes: An Outcome-Wide Umbrella Review of Meta-analyses and Mendelian Randomization Studies.

Elevated levels of homocysteine (Hcy) are associated with various health outcomes. We aimed to systematically assess the credibility and certainty of evidence of associations of Hcy and Hcy-lowering therapies with various health outcomes. We retrieved observational meta-analyses examining the associations between Hcy and health outcomes, interventional meta-analyses investigating health outcomes related to Hcy-lowering treatments, and Mendelian randomization (MR) studies exploring the causal associations of Hcy with health outcomes to perform an umbrella review. A total of 135 observational me

Molecular mechanisms underlying methotrexate-induced intestinal injury and protective strategies.

Methotrexate (MTX) is a folic acid reductase inhibitor that manages various malignancies as well as immune-mediated inflammatory chronic diseases. Despite being frequently prescribed, MTX's severe multiple toxicities can occasionally limit its therapeutic potential. Intestinal toxicity is a severe adverse effect associated with the administration of MTX, and patients are significantly burdened by MTX-provoked intestinal mucositis. However, the mechanism of such intestinal toxicity is not entirely understood, mechanistic studies demonstrated oxidative stress and inflammatory reactions as key fa

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… Cancer Treat Rev 33:448–460 Lopez-Gonzalez JS, Prado-Garcia H, Aguilar-Cazares D, Molina-Guarneros JA, Morales-Fuentes J, Mandoki JJ (2004) Apoptosis and cell cycle disturbances induced by coumarin and 7-hydroxycoumarin on human lung carcinoma cell lines. …

Enhancing the Bioavailability of Resveratrol: Combine It, Derivatize It, or Encapsulate It?

Overcoming the limited bioavailability and extensive metabolism of effective in vitro drugs remains a challenge that limits the translation of promising drugs into clinical trials. Resveratrol, despite its well-reported therapeutic benefits, is not metabolically stable and thus has not been utilized as an effective clinical drug. This is because it needs to be consumed in large amounts to overcome the burdens of bioavailability and conversion into less effective metabolites. Herein, we summarize the more relevant approaches to modify resveratrol, aiming to increase its biological and therapeut

The role of polyamine metabolism in remodeling immune responses and blocking therapy within the tumor immune microenvironment.

The study of metabolism provides important information for understanding the biological basis of cancer cells and the defects of cancer treatment. Disorders of polyamine metabolism is a common metabolic change in cancer. With the deepening of understanding of polyamine metabolism, including molecular functions and changes in cancer, polyamine metabolism as a new anti-cancer strategy has become the focus of attention. There are many kinds of polyamine biosynthesis inhibitors and transport inhibitors, but not many drugs have been put into clinical application. Recent evidence shows that polyamin

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… Morales-Nebreda L, McLafferty FS, Singer BD. DNA Methylation as a transcriptional regulator of the immune system. Transl Res (2019) 204:1–18. doi: 10.1016/j.trsl.2018.08.001 76. Ikeguchi Y, Bewley MC, Pegg AE. Aminopropyltransferases: Function, structure and genetics. …

A systematic literature review informing the consensus statement on efficacy and safety of pharmacological treatment with interleukin-6 pathway inhibition with biological DMARDs in immune-mediated inflammatory diseases.

OBJECTIVES: Informing an international task force updating the consensus statement on efficacy and safety of biological disease-modifying antirheumatic drugs (bDMARDs) selectively targeting interleukin-6 (IL-6) pathway in the context of immune-mediated inflammatory diseases. METHODS: A systematic literature research of all publications on IL-6 axis inhibition with bDMARDs published between January 2012 and December 2020 was performed using MEDLINE, EMBASE and Cochrane CENTRAL databases. Efficacy and safety outcomes were assessed in clinical trials including their long-term extensions and obse

Kabuki Syndrome-Clinical Review with Molecular Aspects.

Kabuki syndrome (KS) is a rare developmental disorder principally comprised of developmental delay, hypotonia and a clearly defined dysmorphism: elongation of the structures surrounding the eyes, a shortened and depressed nose, thinning of the upper lip and thickening of the lower lip, large and prominent ears, hypertrichosis and scoliosis. Other characteristics include poor physical growth, cardiac, gastrointestinal and renal anomalies as well as variable behavioral issues, including autistic features. De novo or inherited pathogenic/likely pathogenic variants in the KMT2D gene are the most c

Neuroinflammatory Process Involved in Different Preclinical Models of Chemotherapy-Induced Peripheral Neuropathy.

Peripheral neuropathies are characterized by nerves damage and axonal loss, and they could be classified in hereditary or acquired forms. Acquired peripheral neuropathies are associated with several causes, including toxic agent exposure, among which the antineoplastic compounds are responsible for the so called Chemotherapy-Induced Peripheral Neuropathy (CIPN). Several clinical features are related to the use of anticancer drugs which exert their action by affecting different mechanisms and structures of the peripheral nervous system: the axons (axonopathy) or the dorsal root ganglia (DRG) ne

Antibody-Drug Conjugates for Cancer Therapy.

Antibody-drug conjugates (ADCs) are novel drugs that exploit the specificity of a monoclonal antibody (mAb) to reach target antigens expressed on cancer cells for the delivery of a potent cytotoxic payload. ADCs provide a unique opportunity to deliver drugs to tumor cells while minimizing toxicity to normal tissue, achieving wider therapeutic windows and enhanced pharmacokinetic/pharmacodynamic properties. To date, nine ADCs have been approved by the FDA and more than 80 ADCs are under clinical development worldwide. In this paper, we provide an overview of the biology and chemistry of each co

Proceedings of the CIMAGO Meeting - Challenges in Oncobiology Coimbra, 31st january 2020.

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Novel Investigations of Flavonoids as Chemopreventive Agents for Hepatocellular Carcinoma.

We would like to highlight the application of natural products to hepatocellular carcinoma (HCC). We will focus on the natural products known as flavonoids, which target this disease at different stages of hepatocarcinogenesis. In spite of the use of chemotherapy and radiotherapy in treating HCC, patients with HCC still face poor prognosis because of the nature of multidrug resistance and toxicity derived from chemotherapy and radiotherapy. Flavonoids can be found in many vegetables, fruits, and herbal medicines that exert their different anticancer effects via different intracellular signalin

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… Morales-González A. Hepatoprotective effect of silymarin World Journal of Hepatology 2014 6 3 144 149 10.4254/wjh.v6.i3.144 24672644 PMC3959115 75 Nishikawa T. Nakajima T. Moriguchi M. …

Anticancer Molecular Mechanisms of Curcuminoids: An Updated Review of Clinical Trials.

Curcuminoids are bioactive polyphenols, mainly extracted from Curcuma longa (turmeric), and have received much attention due to their pleiotropic anticancer properties. Recent evidence suggests that curcumin and analogs prevent the activation of a variety of signaling pathways, including the MAPK, PI3K/Akt, and NF-kB pathways, resulting in the induction of apoptosis, prevention of proliferation, and suppression. In addition to these processes, curcumin has been shown to enhance the efficacy of the conventional anti-cancer modalities such as radiation and chemotherapy. By suppressing the expres

Эффективность Куркумина в нейродегенеративных болезнях: от фармакокинетических барьеров до передовых систем доставки.

Предыстория и цели: Основные нейродегенеративные заболевания (НД) - болезнь Альцгеймера (AD), болезнь Паркинсона (PD), множественный склероз (MS) и амиотропический боковой склероз (ALS) - создают растущее бремя для здоровья людей во всем мире при отсутствии доступных методов лечения, позволяющих вести борьбу с заболеваниями. Куркумин, полифенол из Curcuma longa, является многообещающим кандидатом из-за его плейотропного антиоксиданта, антивоспалительного и нейрозащитного профиля, наблюдаемого главным образом в доклинических моделях, но плохой оральной биодоступности ().<1%) и незначительное пр

HDACs and Their Inhibitors on Post-Translational Modifications: The Regulation of Cardiovascular Disease.

Cardiovascular diseases (CVD), such as myocardial hypertrophy, heart failure, atherosclerosis, and myocardial ischemia/reperfusion (I/R) injury, are among the major threats to human health worldwide. Post-translational modifications alter the function of proteins through dynamic chemical modification after synthesis. This mechanism not only plays an important role in maintaining homeostasis and plays a crucial role in maintaining normal cardiovascular function, but is also closely related to the pathological state of various diseases. Histone deacetylases (HDACs) play an important role in the

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… Castillo E.C., Morales J.A., Chapoy-Villanueva H., Silva-Platas C., Treviño-Saldaña N., Guerrero-Beltrán C.E., Bernal-Ramírez J., Torres-Quintanilla A., García N., Youker K., et al. …

Plasma Cell Myeloma: Биохимический анализ диагноза, лечения и умного нанокарьера - терапевтического развития.

Плазменная миелома (ПХМ) классифицируется как рак крови и характеризуется аномальным распространением плазменных клеток в костном мозге и чрезмерным производством моноколональных иммуноглобулинов, что приводит к постоянному повреждению жизненно важных органов. Несмотря на то, что стратегии лечения улучшились благодаря разработке протеазонных ингибиторов (ИП), иммуноводных препаратов (ИМИД) и моноклонных антител (mAbs), ПХМ остается неизлечимым заболеванием из-за молекулярной неоднородности и развития сопротивляемости лекарствам. В этом обзоре мы обсуждаем биохимические и молекулярные основы, л

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

Chemotherapy-induced acute kidney injury: epidemiology, pathophysiology, and therapeutic approaches.

Despite significant advancements in oncology, conventional chemotherapy remains the primary treatment for diverse malignancies. Acute kidney injury (AKI) stands out as one of the most prevalent and severe adverse effects associated with these cytotoxic agents. While platinum compounds are well-known for their nephrotoxic potential, other drugs including antimetabolites, alkylating agents, and antitumor antibiotics are also associated. The onset of AKI poses substantial risks, including heightened morbidity and mortality rates, prolonged hospital stays, treatment interruptions, and the need for

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… Williams RP, Ferlas BW, Morales PC, Kurtzweil AJ. Mannitol for the prevention of cisplatin-induced nephrotoxicity: A retrospective comparison of hydration plus mannitol versus hydration alone in inpatient and outpatient regimens at a large academic medical center. …

Bispecific Antibodies in Hematological Malignancies: A Scoping Review.

Bispecific T-cell engagers (BiTEs) and bispecific antibodies (BiAbs) have revolutionized the treatment landscape of hematological malignancies. By directing T cells towards specific tumor antigens, BiTEs and BiAbs facilitate the T-cell-mediated lysis of neoplastic cells. The success of blinatumomab, a CD19xCD3 BiTE, in acute lymphoblastic leukemia spearheaded the expansive development of BiTEs/BiAbs in the context of hematological neoplasms. Nearly a decade later, numerous BiTEs/BiAbs targeting a range of tumor-associated antigens have transpired in the treatment of multiple myeloma, non-Hodgk

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… Jiménez-Morales S., Aranda-Uribe I.S., Pérez-Amado C.J., Ramírez-Bello J., Hidalgo-Miranda A. Mechanisms of Immunosuppressive Tumor Evasion: Focus on Acute Lymphoblastic Leukemia. Front. Immunol. 2021;12:737340. doi: 10.3389/fimmu.2021.737340. 95. …

Revisiting Proteasome Inhibitors: Molecular Underpinnings of Their Development, Mechanisms of Resistance and Strategies to Overcome Anti-Cancer Drug Resistance.

Proteasome inhibitors have shown relevant clinical activity in several hematological malignancies, namely in multiple myeloma and mantle cell lymphoma, improving patient outcomes such as survival and quality of life, when compared with other therapies. However, initial response to the therapy is a challenge as most patients show an innate resistance to proteasome inhibitors, and those that respond to the therapy usually develop late relapses suggesting the development of acquired resistance. The mechanisms of resistance to proteasome inhibition are still controversial and scarce in the literat

High-Dose Vitamin C in Advanced-Stage Cancer Patients.

High-dose intravenously administered vitamin C (IVC) is widely used in cancer patients by complementary and alternative medicine practitioners. The most frequent indications for IVC therapy result from the belief in its effectiveness as a potent anti-cancer agent which additionally enhances chemosensitivity of cancer cells and reduces chemotherapy-related toxicities and fatigue intensity. In this narrative review, we decided to deal with this issue, trying to answer the question whether there is any scientific evidence supporting the rationale for application of high-dose IVC therapy in advanc

A Review on Curability of Cancers: More Efforts for Novel Therapeutic Options Are Needed.

Cancer remains a major cause of death globally. Given its relapsing and fatal features, curing cancer seems to be something hardly possible for the majority of patients. In view of the development in cancer therapies, this article summarizes currently available cancer therapeutics and cure potential by cancer type and stage at diagnosis, based on literature and database reviews. Currently common cancer therapeutics include surgery, chemotherapy, radiotherapy, targeted therapy, and immunotherapy. However, treatment with curative intent by these methods are mainly eligible for patients with loca

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… Morales-Orue I. Castilla-Martinez J. Zafra-Martin J. Kannemann A. Blanco J. Lloret M. Lara P.C. Stereotactic Ablative Radiotherapy Combined with Immune Checkpoint Inhibitors Reboots the Immune Response Assisted by Immunotherapy in Metastatic Lung Cancer: A Systematic Review Int. J. Mol. …