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mRNA вакцины для профилактики и лечения заболеваний.

mRNA вакцины стали высокоэффективными стратегиями в области профилактики и лечения болезней, в значительной степени, хотя и не полностью благодаря их выдающимся показателям в последние годы в борьбе с глобальной чумой. COVID-19. Огромное превосходство вакцин MRNA в том, что касается их эффективности, безопасности и крупномасштабного производства, побуждает фармацевтическую промышленность и биотехнологические компании распространять их применение на различные заболевания, несмотря на несомненные проблемы в проектировании, изготовлении и способе управления. В настоящем обзоре рассматриваются тех

Cutting edge of immune response and immunosuppressants in allogeneic and xenogeneic islet transplantation.

As an effective treatment for diabetes, islet transplantation has garnered significant attention and research in recent years. However, immune rejection and the toxicity of immunosuppressive drugs remain critical factors influencing the success of islet transplantation. While immunosuppressants are essential in reducing immune rejection reactions and can significantly improve the survival rate of islet transplants, improper use of these drugs can markedly increase mortality rates following transplantation. Additionally, the current availability of islet organ donations fails to meet the demand

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… A 14-patient Phase 1/2a study in New Zealand showed that neonatal porcine islets encapsulated with alginate-poly-L-ornithine-alginate (APA) were safe and reduced unawareness of hypoglycemia in patients with type 1 diabetes ( 221 ). … The use of multivalent cations (Ca² + , Ba² + ) and polycations (poly-L-lysine or poly-L-ornithine) during alginate synthesis alters its properties ( 231 ). …

Fanconi syndrome induced by adefovir dipivoxil: a case report and clinical review.

More than 150 cases of Fanconi syndrome (FS) or hypophosphatemia osteomalacia induced by low-dose adefovir dipivoxil (ADV) have been reported since 2002, when ADV was introduced for the long-term treatment of hepatitis B virus (HBV) infection. Because the life expectancy of HBV-infected individuals has increased, the adverse effects of long-term treatment with antiviral therapies are increasingly observed, and nephrotoxicity is one of the most severe adverse effects of ADV. Therefore, the number of cases may be far higher than reported. Moreover, ADV-induced FS is often misdiagnosed or diagnos

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… Some biomarkers of hepatic mitochondria impairment have been described, such as glutamate dehydrogenase, carbamoyl phosphate synthase-1, alanine aminotransferase-2, and ornithine carbamoyltransferase, but no kidney mitochondria-specific enzymes have been recognized to date. …

Occult cirrhosis presenting as progressive tremor: acquired hepatocerebral degeneration induced by traditional Chinese medicine and natural health products, aggravated by manganese supplements: A case report.

RATIONALE: Acquired hepatocerebral degeneration (AHD) is a rare neurological complication of chronic liver disease or portosystemic shunting, typically characterized by extrapyramidal symptoms and manganese accumulation in the basal ganglia. Its diagnosis is particularly challenging in patients with occult cirrhosis and complex exposure histories, especially when traditional Chinese medicines (TCM) and natural health products (NHPs) contribute to hepatotoxicity. PATIENT CONCERNS: A 66-year-old woman presented with a 2-year history of progressive postural and intention tremor, with marked wors

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… Specifically, management included the use of bicyclol tablets and polyene phosphatidylcholine capsules to reduce hepatic enzyme levels, and L-ornithine L-aspartate injection to lower blood ammonia level. …

Fanconi syndrome induced by the long-term use of tenofovir disoproxil fumarate: a case report and literature review.

We present the case of a woman of 50 years of age who experienced widespread bone pain along with digestive symptoms, including nausea and vomiting. She had been prescribed tenofovir disoproxil fumarate (TDF) tablets for the treatment of hepatitis B. Laboratory testing revealed low circulating phosphorus and potassium concentrations and acidosis. A whole-body bone scan revealed abnormal bone metabolism. Rheumatologic and urologic conditions were ruled out, and therefore TDF-induced Fanconi syndrome (FS) and related bone pain was diagnosed. After the TDF was discontinued, the patient's symptoms

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… Heavy metals (e.g., lead, cadmium, mercury, copper), L-arginine and L-ornithine, aristolochic acid (a cause of herbal nephropathy), and fumaric acid are some other factors that cause FS. 3 – 11 Of these, drugs are the most frequent cause of FS. 7 Tenofovir disoproxil fumarate (TDF) is an NRTI antiviral …

Построение олигодендроцитов, подобных прекурсорам, из эмбриональных фибробатластов мыши с использованием miR-7a Имитация.

ЦЕЛИ: Разработка эффективных стратегий повышения эффективности мер по ликвидации последствий по-прежнему является одной из основных терапевтических проблем в связи с такими демиелинизирующими расстройствами, как множественный склероз (МС). МикроРНК (миРНК) стали мощным регулятором клеточной судьбы. Было показано, что miR-7a , в значительной степени выражается в олигодендроцитных клетках-прекурсорах (ОПК). Цель этого исследования заключалась в изучении вопроса о том, является ли завышенное выражение мнений miR-7a :: может перепрограммировать эмбриональные фибробатласты мыши (МЭФ) в похожие на O

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… Induction of OPC-like phenotype in MEFs To test whether miR-7a overexpression could reprogram MEFs toward an OPC-like fate, cells at passages 4–5 were seeded onto poly-L-ornithine/laminin-coated coverslips in 24-well plates. …

Emerging Therapies for Hepatocellular Carcinoma (HCC).

Hepatocellular carcinoma (HCC) arises from hepatocytes and accounts for 90% of primary liver cancer. According to Global Cancer Incidence, Mortality and Prevalence (GLOBOCAN) 2020, globally HCC is the sixth most common cancer and the third most common cause of cancer-related deaths. Reasons for HCC prognosis remaining dismal are that HCC is asymptomatic in its early stages, leading to late diagnosis, and it is markedly resistant to conventional chemo- and radiotherapy. Liver transplantation is the treatment of choice in early stages, while surgical resection, radiofrequency ablation (RFA) and

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… Apoptin, a tumor-specific apoptosis-inducing protein, was loaded onto ornithine-conjugated PAMAM, and showed better transfection efficiency and intracellular uptake, which lead to apoptosis in HepG2 cells compared to PAMAM dendrimer alone [ 27 ]. … Apoptin gene delivery by the functionalized polyamidoamine (PAMAM) dendrimer modified with ornithine induces cell death of hepg2 cells. Polymers. 2017;9:197. doi: 10.3390/polym9060197. 28. Rajasekaran D., Srivastava J., Ebeid K., Gredler R., Akiel M., Jariwala N., Robertson C.L., Shen X. …

The 8p11 myeloproliferative syndrome: Genotypic and phenotypic classification and targeted therapy.

EMS(8p11 myeloproliferative syndrome, EMS) is an aggressive hematological neoplasm with/without eosinophilia caused by a rearrangement of the FGFR1 gene at 8p11-12. It was found that all cases carry chromosome abnormalities at the molecular level, not only the previously reported chromosome translocation and insertion but also a chromosome inversion. These abnormalities produced 17 FGFR1 fusion genes, of which the most common partner genes are ZNF198 on 13q11-12 and BCR of 22q11.2. The clinical manifestations can develop into AML (acute myeloid leukemia), T-LBL (T-cell lymphoblastic lymphoma),

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… Exons 3-8 encode a central ornithine exchange factor domain (GEF), and exons 19-23 contain the Racgap domain, as well as other PSD95, D1g1, and ZO-1 (PDZ) domain binding motifs ( 26 , 51 ). There is evidence that several domains of BCR play a crucial role in the pathogenesis of EMS. … The fusion protein contains part of the RhoGEF (Rho ornithine exchange factor) domain of BCR, and it has kinase activity. The BCR-FGFR1 fusion causes a kinase-kinase fusion, it is where the tyrosine kinase domain of FGFR1 is fused to the serine-threonine kinase domain of BCR ( 13 ). …

High Output Heart Failure in Multiple Myeloma: Pathogenetic Considerations.

The high output heart failure is a clinical condition in which the systemic congestion is associated to a high output state, and it can be observed in a non-negligible percentage of hematological diseases, particularly in multiple myeloma, a condition in which the risk of adverse cardiovascular events may increase, with a worse prognosis for patients. For this reason, though an accurate literature search, we provided in this review a complete overview of different pathogenetic mechanisms responsible for high output heart failure in multiple myeloma. Indeed, this clinical finding is present in

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… It has been said that myeloma cells, through the enhanced activity of glutamminolysis, increase the levels of ammonaemia, and the latter largely uses the ureagenesis pathway with arginine as the final metabolite; in turn, arginine can be transformed in ornithine by hepatic arginase or it be a NO precursor …

Exosomal circRNAs: Deciphering the novel drug resistance roles in cancer therapy.

Exosomal circular RNA (circRNAs) are pivotal in cancer biology, and tumor pathophysiology. These stable, non-coding RNAs encapsulated in exosomes participated in cancer progression, tumor growth, metastasis, drug sensitivity and the tumor microenvironment (TME). Their presence in bodily fluids positions them as potential non-invasive biomarkers, revealing the molecular dynamics of cancers. Research in exosomal circRNAs is reshaping our understanding of neoplastic intercellular communication. Exploiting the natural properties of exosomes for targeted drug delivery and disrupting circRNA-mediate

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… Zhang et al. [ 74 ] discovered that circ_0003028 facilitates tumor progression by modulating the miR-498/ornithine decarboxylase 1 (ODC1) axis. circ_0003028 is upregulated in HCC, promoting cell proliferation, metastasis, and triggering the epithelial–mesenchymal transition (EMT) by its exosome pathway … Circular RNA circ_0003028 regulates cell development through modulating miR-498/ornithine decarboxylase 1 axis in hepatocellular carcinoma. Anti Cancer Drugs. 2023;34:507–518. doi: 10.1097/CAD.0000000000001457. 75. Qin L., Zhan Z., Wei C., et al. …

Роль микроглии в множественном склерозе: последствия для лечения ингибиторами тиросина Брютона.

Множественный склероз (MS) — хроническое аутоиммунное заболевание, затрагивающее центральную нервную систему (CNS), характеризующееся воспалением и нейродегенерацией. Патофизиология MS, особенно его прогрессивные формы, включает различные клеточные компоненты, включая микроглию, являющиеся основными постоянными иммунными клетками CNS. В настоящем обзоре рассматривается роль микроглии в нейроинфламмации, ремонте тканей и нейронном гомеостазе, а также их участие в MS и изучаются потенциальные терапевтические стратегии, ориентированные на микроглиальную функцию.МЕТОДЫ: Поиск литературы, проведенн

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… The use of oxidative metabolism allows the microglia to maintain their neuroprotective functions and contributes to tissue repair and wound healing in the longer term; the production of ornithine by anti-inflammatory microglia as part of glutaminolysis enhances cell proliferation and repair ( 33 ). …

Peroral Endoscopic Myotomy (POEM) in a Patient with Complete Heart Block-a Case Report.

UNLABELLED: The ATP-binding cassette, subfamily G, member 2 (ABCG2) transporter, or breast cancer resistance protein (BCRP), plays a crucial role in the absorption and distribution of various compounds, including anti-seizure medications (ASMs). ABCG2 genetic polymorphisms have been shown to affect the pharmacokinetics of several drugs, including anti-cancer drugs and statins. Clinical studies suggested an association between the ABCG2 variations and ASMs pharmacokinetics. Thus, the aim of the present study was to evaluate the effect of the coding ABCG2 variants, 742T > G and 886G > C on the A

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… Raper SE Chirmule N Lee FS Wivel NA Bagg A Gao GP Wilson JM Batshaw ML Fatal systemic inflammatory response syndrome in a ornithine transcarbamylase deficient patient following adenoviral gene transfer Mol Genet Metab 2003 80 148 158 10.1016/j.ymgme.2003.08.016 14567964 10. …

Chemoprevention in Skin Cancer: What Advice?

The incidence of melanoma and non-melanoma skin cancers (NMSCs) is increasing worldwide. While NMSCs are more common, melanoma remains the most challenging because of its higher aggressiveness. Although the use of sunscreens is key in high-risk populations, it provides limited protection, which highlights the need for alternative solutions. In this review, we discuss current evidence on chemopreventive therapies, as well as their efficacy and adverse events, including immunocompetent and immunosuppressed patients. Acitretin, nicotinamide, 5-fluorouracil, and photodynamic therapy have shown ove

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… Difluoromethylornithine Difluoromethylornithine (DFMO) is an irreversible inhibitor of the ornithine decarboxylase enzyme involved in polyamine synthesis, needed for cell growth and proliferation ( Figure 5 ) [ 50 ]. … Evidence coming from preclinical models suggests that inhibition of the ornithine decarboxylase will prevent tumor formation [ 50 ]. Several studies have focused on the use of DMFO as a chemopreventive agent in a range of cancers, including skin cancers, with variable results. …

A Comprehensive Review of the Diagnosis and Management of Acute Liver Failure.

Acute liver failure (ALF) is a rare and specific form of severe hepatic dysfunction characterized by coagulopathy and hepatic encephalopathy in a patient with no known liver disease. ALF carries a high morbidity and mortality. Careful attention should be given to hemodynamics and metabolic parameters along with the active surveillance of infections. Timely transfer and supportive management are important in an intensive care unit in a liver transplant center. Identifying patients who will and will not improve with medical management and may need emergent liver transplantation is critical. In t

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… Empiric use of treatments to reduce ICP, including hypertonic saline, l-ornithine l-aspartate (LOLA), mannitol, hyperventilation, or moderate hypothermia, has not been shown to improve mortality in ALF [ 2 , 21 ]. Benzodiazepines and opioids should be avoided and sedation should be minimized. …

Clinical Trials of Stem Cell Therapy in Japan: The Decade of Progress under the National Program.

Stem cell therapy is a current world-wide topic in medical science. Various therapies have been approved based on their effectiveness and put into practical use. In Japan, research and development-related stem cell therapy, generally referred to as regenerative medicine, has been led by the government. The national scheme started in 2002, and support for the transition to clinical trials has been accelerating since 2011. Of the initial 18 projects that were accepted in the budget for preclinical research, 15 projects have begun clinical trials so far. These include the transplantation of retin

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… Hepatocyte transplantation using a living donor reduced graft in a baby with ornithine transcarbamylase deficiency: A novel source of hepatocytes Liver Transpl. 2014 20 391 393 10.1002/lt.23800 24273015 23. Akutsu H. Nasu M. Morinaga S. Motoyama T. Homma N. Machida M. Yamazaki-Inoue M. Okamura K. …

Breakthroughs in Medicinal Chemistry: New Targets and Mechanisms, New Drugs, New Hopes-5.

Breakthroughs in Medicinal Chemistry: New Targets and Mechanisms, New Drugs, New Hopes is a series of Editorials which is published on a biannual basis by the Editorial Board of the Medicinal Chemistry section of the journal Molecules [...].

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… Inspired by Svendsen and co-workers [ 14 ], who defined the pharmacophore of AMPs as two cationic charges and two bulky hydrophobic aromatic units, Boullet et al. [ 15 ], with the idea of keeping the AMPs simple and stable, synthetized new β 2,2 - and β 3,3 -bis- homo -ornithine/arginine peptides. …

Temsirolimus in the treatment of relapsed and/or refractory mantle cell lymphoma.

Patients with mantle cell lymphoma (MCL) have a poor prognosis; consequently, new therapeutic approaches, such as rapamycin and its derivates, mammalian target of rapamycin (mTOR) inhibitors, are warranted. Temsirolimus (also known as CCI-779), a dihydroester of rapamycin, in MCL cell lines inhibited mTOR, downregulated p21 and v-Raf, and induced autophagy. The first clinical trial in MCL patients was performed using 250 mg of temsirolimus weekly for 6-12 cycles. The overall response rate was 38%; the median time to progression was 6.5 months, median overall survival was 12 months, and the med

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… The mTOR-mediated phosphorylation of 4E-BP1 diminishes the stability of the 4E-BP1/eIF4E complex and facilitates the eIF4E action, enhancing translation of several mRNAs, such as cyclin D1, c-myc, hypoxia-inducible factor 1α (HIF1α), ornithine decarboxylase, VEGF, fibroblast growth factor, and ribosomal …

Возраст и стадия созревания связаны с последствиями фибриногена для человека Олигодендроголии.

Фибриноген — это протеин, полученный из крови и содержащийся в коагуляции, и он может проникнуть в центральную нервную систему (КНС) после разрушения мозгового барьера. Эта молекула была связана с множественным склерозом (MS), заболеванием, отмеченным воспалением и обезвоживанием в CNS. Однако воздействие этой молекулы не изучалось на миелионирующих клетках человека. В этом исследовании рассматривается вопрос о том, как фибриноген влияет на родственные клетки человека олигодендроцита (OL) на различных этапах развития. Используя индуцированные плюрипотентные стволовые клетки (iPSC) прекурсоры O

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… According to a previously published protocol (Piscopo et al. 2024 ), early OL‐lineage progenitors were generated and plated on poly‐L‐ornithine (Sigma‐Aldrich, Oakville ON)/laminin (Invitrogen, Waltham MA) coated culture vessels. …

Роль окситоцина и Васопрессина в нейропсихиатрических расстройствах: терапевтический потенциал агонистов и антагонистов.

Окситоцин (OT) и вазопрессин (AVP) являются гипоталамическими нейропептидами, которые традиционно ассоциируются с их регулирующей ролью в размножении, гомеостазисе воды и социальном поведении. Интересно, что в последние годы эта роль расширилась и эти нейропептиды стали лечебными мишенями для различных нейропсихиатрических заболеваний, таких, как аутизм, зависимость, шизофрения, депрессия и тревожное расстройство. В связи с химическими и физическими характеристиками этих нейропептидов, включая короткий период полураспада, плохое проникновение через мозговые барьеры, беспорядочность для AVP и O

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… Ornithine vasotocin or OTA, is a selective peptide OT-R antagonist, which has been used to study the role of the OT system in attachment behaviors between the mother and offspring before weaning. …

Multiplatform plasma fingerprinting in cancer cachexia: a pilot observational and translational study.

BACKGROUND: Cachexia is a metabolic syndrome that affects up to 50-80% of cancer patients. The pathophysiology is characterized by a variable combination of reduced food intake and abnormal metabolism, including systemic inflammation and negative protein and energy balance. Despite its high clinical significance, defined diagnostic criteria and established therapeutic strategies are lacking. The 'omics' technologies provide a global view of biological systems. We hypothesize that blood-based metabolomics might identify findings in cachectic patients that could provide clues to gain knowledge o

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… Asparagine | C 4 H 8 N 2 O 3 | 132.0535 | 15.86 | 3 | 0.0092 | 1.2 | JK | 0.68 | CE | Putative | ESI+ Arginine | C 6 H 14 N 4 O 2 | 174.1117 | 11.52 | 1 | 0.0087 a | 1.8 | JK | 0.44 | CE | Putative | ESI+ Citrulline | C 6 H 13 N 3 O 3 | 175.0957 | 16.65 | 1 | 0.021 | 1.3 | JK | 0.54 | CE | Putative | ESI+ Ornithine …