Endothelin-1 in Health and Disease

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(14), P. 11295 - 11295

Published: July 10, 2023

Discovered almost 40 years ago, the potent vasoconstrictor peptide endothelin-1 (ET-1) has a wide range of roles both physiologically and pathologically. In recent years, there been focus on contribution ET-1 to disease. This led development various ET receptor antagonists, some which are approved for treatment pulmonary arterial hypertension, while clinical trials other diseases have numerous yet, most part, unsuccessful. However, given vast physiological impact ET-1, it is surprising disappointing that therapeutics targeting pathway remain limited. Strategies aimed at pathways influencing synthesis release could provide new therapeutic avenues, yet research using cultured cells in vitro had little follow up intact ex vivo preparations. article summarises what currently known about synthesis, storage as well role several including cardiovascular diseases, COVID-19 chronic pain. Unravelling identifying targets potential treat many whether through disease prevention, slowing progression or reversing pathology.

Language: Английский

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The immunostimulatory nature of mRNA lipid nanoparticles

Advanced Drug Delivery Reviews, Journal Year: 2024, Volume and Issue: 205, P. 115175 - 115175

Published: Jan. 11, 2024

Language: Английский

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COVID-19 mRNA Vaccines: Lessons Learned from the Registrational Trials and Global Vaccination Campaign

Cureus, Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 24, 2024

Our understanding of COVID-19 vaccinations and their impact on health mortality has evolved substantially since the first vaccine rollouts. Published reports from original randomized phase 3 trials concluded that mRNA vaccines could greatly reduce symptoms. In interim, problems with methods, execution, reporting these pivotal have emerged. Re-analysis Pfizer trial data identified statistically significant increases in serious adverse events (SAEs) group. Numerous SAEs were following Emergency Use Authorization (EUA), including death, cancer, cardiac events, various autoimmune, hematological, reproductive, neurological disorders. Furthermore, products never underwent adequate safety toxicological testing accordance previously established scientific standards. Among other major topics addressed this narrative review are published analyses harms to humans, quality control issues process-related impurities, mechanisms underlying (AEs), immunologic basis for inefficacy, concerning trends based registrational data. The risk-benefit imbalance substantiated by evidence date contraindicates further booster injections suggests that, at a minimum, should be removed childhood immunization program until proper studies conducted. Federal agency approval blanket-coverage population-wide had no support an honest assessment all relevant commensurate consideration risks versus benefits. Given extensive, well-documented unacceptably high harm-to-reward ratio, we urge governments endorse global moratorium modified questions pertaining causality, residual DNA, aberrant protein production answered.

Language: Английский

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Plaque Psoriasis Exacerbation and COVID-19 Vaccination: Assessing the Characteristics of the Flare and the Exposome Parameters

Vaccines, Journal Year: 2024, Volume and Issue: 12(2), P. 178 - 178

Published: Feb. 9, 2024

The diverse patient population and widespread vaccination in the COVD-19 era make vaccine-triggered episodes of psoriasis an ideal model exposome research. This scenario explores fine balance between protective exacerbating factors, providing insights into complex relationship environmental exposure immunopathogenesis when a trigger appears, such as that hyperinflammatory state induced by COVID-19 vaccine. Analyzing interactions vaccine-induced phenomena parameters may provide clinically relevant information important for personalized medicine decision-making. We performed literature review seeking patients with plaque flares or new onset change another subtype, pustular erythrodermic flare, focusing on inner external traits patients. identified 71 flares, 12 new-onset psoriasis, 17 subtype change, assessed terms clinical presentation, post-vaccination flare period treatment status, well (genomics, oxidative stress, hormonal impact due to gender, aging, skin color) (UV, infectomics). Novel data following are primarily obtained combining episode features characteristics comparing them similar unrelated vaccination.

Language: Английский

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Integrative Korean medicine for recurrent lumbar disc herniation after coronavirus disease vaccination: A case report and literature review

Medicine, Journal Year: 2025, Volume and Issue: 104(1), P. e41079 - e41079

Published: Jan. 3, 2025

Many side effects have been associated with the coronavirus disease (COVID-19) vaccine. While most adverse events (AEs) are mild, serious occasionally observed in neurological and musculoskeletal systems. Nevertheless, articles reporting such after COVID-19 vaccination limited, only few case reports detailed descriptions available literature. Herein, we report of a 41-year-old male office worker who developed symptoms recurrent disc herniation 2 days vaccination; patient had no other factors that may caused recurrence herniation, as excessively vigorous activities, following vaccination. Consequently, was suspected having cauda equina syndrome owing to lumbar he underwent surgery. The integrative Korean medicine treatment, including acupuncture, pharmacopuncture, Chuna manual therapy, for 8 months postoperatively. After patient's postoperative complications improved; Numerical Rating Scale score changed from 5 1, Oswestry Disability Index 30 3. A literature review showed various cases related inflammation or immune-mediated pathogenesis. This paper confirmed possibility COVID is an effective treatment option

Language: Английский

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COVID-19 Modified mRNA “Vaccines”: Lessons Learned from Clinical Trials, Mass Vaccination, and the Bio-Pharmaceutical Complex, Part 1

International Journal of Vaccine Theory Practice and Research, Journal Year: 2024, Volume and Issue: 3(2), P. 1112 - 1178

Published: June 29, 2024

Our understanding of COVID-19 synthetic, modified mRNA (modmRNA) products and their public health impact has evolved substantially since December 2020. Published reports from the original randomized placebo-controlled trials concluded that modmRNA injections could greatly reduce symptoms. However, premature termination both obviated any reliable assessment potential adverse events due to an insufficient timeframe for proper safety evaluation. Following authorization global distribution, problems with methods execution have emerged. The usual testing protocols toxicology requirements were bypassed. Many key trial findings either misreported or omitted entirely published reports. By implication, secondary estimates excess morbidity mortality in must be deemed underestimates. Rigorous re-analyses data post-marketing surveillance studies indicate a substantial degree modmRNA-related harms than was initially reported. Confidential Pfizer documents had revealed 1.6 million by August 2022. A third serious injuries cardiovascular, neurological, thrombotic, immunological, reproductive systems, along alarming increase cancers. Moreover, well-designed shown repeated cause immune dysfunction, thereby potentially contributing heightened susceptibility SARS-CoV-2 infections increased risks COVID-19. This paper also discusses insidious influence Bio-Pharmaceutical Complex, closely coordinated collaboration between organizations, pharmaceutical companies, regulatory agencies. We recommend moratorium on until toxicological are conducted.

Language: Английский

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COVID-Vaccines in Pregnancy: Maternal and Neonatal Response over the First 9 Months after Delivery

Biomolecules, Journal Year: 2024, Volume and Issue: 14(4), P. 435 - 435

Published: April 3, 2024

Vaccination against SARS-CoV-2 has been demonstrated to be safe during gestation. Nevertheless, there are no robust data investigating the entity of maternal antibodies’ transmission through placenta newborn and persistence antibodies in babies’ serum. The objective this study is assess antibody kinetics among newborns first months life. Women having received one or two doses anti-SARS-CoV-2 mRNA-vaccines pregnancy at any gestational age, their newborns, were recruited followed-up over 9 months. Ninety-eight women 103 babies included. At birth, we observed a significant positive correlation between neonatal serum levels negative time since last dose mothers with doses. Over follow-up, birth level significantly decreased according number 3, 6, During registered 34 dyad infection cases. decreasing trend was slower group breastfed non-infected babies. Antibodies from vaccination efficiently transferred via potentially even breast milk. Among show relevant durability

Language: Английский

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Advancement in the development of mRNA‐based vaccines for respiratory viruses

Immunology, Journal Year: 2024, Volume and Issue: 173(3), P. 481 - 496

Published: Aug. 19, 2024

Acute respiratory infections are the leading cause of death and illness in children under 5 years old represent a significant burden older adults. Primarily caused by viruses infecting lower tract, symptoms include cough, congestion, low-grade fever, potentially to bronchiolitis pneumonia. Messenger ribonucleic acid (mRNA)-based vaccines biopharmaceutical formulations that employ mRNA molecules induce specific immune responses, facilitating expression viral or bacterial antigens promoting immunization against infectious diseases. Notably, this technology had relevance during COVID-19 pandemic, as these helped limit SARS-CoV-2 virus infections, hospitalizations, deaths. Importantly, promise be implemented new alternatives for fighting other viruses, such influenza, human syncytial virus, metapneumovirus. This review article analyzes mRNA-based vaccines' main contributions, perspectives, challenges, implications viruses.

Language: Английский

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In response to "Constrictive Pericarditis Associated with COVID-19 or Vaccination"

Balkan Medical Journal, Journal Year: 2025, Volume and Issue: 42(1), P. 89 - 89

Published: Jan. 3, 2025

Language: Английский

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mRNA vaccine-induced SARS-CoV-2 spike-specific IFN-γ and IL-2 T-cell responses are predictive of serological neutralization and are transiently enhanced by pre-existing cross-reactive immunity

Journal of Virology, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 31, 2025

The contributions of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific T cells to vaccine efficacy and durability are unclear. We investigated relationships between mRNA vaccine-induced spike-specific interferon- gamma (IFN-γ) interleukin-2 (IL-2) T-cell responses neutralizing antibody development in long-term care home staff doubly vaccinated with BNT162b2 or mRNA-1273. impacts pre-existing cross-reactive immunity on cellular humoral vaccination were additionally assessed. Mathematical modeling the kinetics IFN-γ IL-2 over 6 months post-second dose was bifurcated into recipients who exhibited gradual increases doubling times 155 167 days decreases half-lives 165 132 days, respectively. Differences did not correlate clinical phenotypes. Serological anti-spike IgG, anti-receptor binding domain (RBD) IgA, anti-RBD IgA levels otherwise decayed all participants 63, 57, 79, 46 respectively, alongside waning capacity (t1/2 = 408 days). Spike-specific induced at 2-6 weeks positively correlated live viral neutralization dose, especially hybrid immune individuals. Participants SARS-CoV-2 greater responses, reduced levels, a trending increase dose. Non-spike-specific T-cells predominantly targeted non-structural protein participants. lastly shown induce off-target against unrelated antigens. In summary, appeared influence serological capacity, only modest effect by cross-reactivity. Our findings provide valuable insights potential both uninfected recipients. study sheds light precise magnitude vaccination. Accordingly, our data will help optimize next-generation cell-based vaccines regimens maximize durability.

Language: Английский

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