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Autism is a neurodevelopmental disorder, the prevalence of which has increased dramatically in the United States over the past two decades. It is characterized by stereotyped behaviors and impairments in social interaction and communication. In this paper, we present evidence that autism can be viewed as a PIN1 deficiency syndrome. Peptidyl-prolyl cis/trans isomerase, NIMA-Interacting 1 (PIN1) is a peptidyl-prolyl cis/trans isomerase, and it has widespread influences in biological organisms. Broadly speaking, PIN1 deficiency is linked to many neurodegenerative diseases, whereas PIN1 over-expression is linked to cancer. Death-associated protein kinase 1 (DAPK1) strongly inhibits PIN1, and the hormone melatonin inhibits DAPK1. Melatonin deficiency is strongly linked to autism. It has recently been shown that glyphosate exposure to rats inhibits melatonin synthesis as a result of increased glutamate release from glial cells and increased expression of metabotropic glutamate receptors. Glyphosate's inhibition of melatonin leads to a reduction in PIN1 availability in neurons. In this paper, we show that PIN1 deficiency can explain many of the unique morphological features of autism, including increased dendritic spine density, missing or thin corpus callosum, and reduced bone density. We show how PIN1 deficiency disrupts the functioning of powerful high-level signaling molecules, such as nuclear factor erythroid 2-related factor 2 (NRF2) and p53. Dysregulation of both of these proteins has been linked to autism. Severe depletion of glutathione in the brain resulting from chronic exposure to oxidative stressors and extracellular glutamate leads to oxidation of the cysteine residue in PIN1, inactivating the protein and further contributing to PIN1 deficiency. Impaired autophagy leads to increased sensitivity of neurons to ferroptosis. It is imperative that further research be conducted to experimentally validate whether the mechanisms described here take place in response to chronic glyphosate exposure and whether this ultimately leads to autism.
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Taurine haloamines, N-chlorotaurine (NCT, TauCl), and N-bromotaurine (NBT, TauBr) are formed by a reaction between taurine and hypohalous acids, HOCl and HOBr, respectively. The major source of endogenous taurine haloamines is neutrophils. Both NCT and NBT share strong anti-inflammatory and microbicidal activities supported by an absence of microbial resistance. In the light of these properties, a number of clinical studies have been performed to document their effectiveness in treatment of bacterial, fungal, and viral infections. The administration of NCT and NBT has been limited to topical application, as they are decomposed upon systemic delivery. This review summarizes current knowledge concerning the therapeutic use of NCT and NBT mainly in various skin disorders such as non-healing wounds, acne vulgaris, herpes zoster, and psoriasis. Moreover, the beneficial effect of NCT inhalation in early stages of COVID-19 and other viral respiratory infections is discussed. And finally, we would like to suggest that NCT might be used to inhibit the development of the cytokine storm through its capacity to suppress the production of IL-6.
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Tratamiento Farmacológico de COVID-19 , Enfermedades Transmisibles , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , Enfermedades Transmisibles/tratamiento farmacológico , Halógenos , Humanos , Neutrófilos , Taurina/farmacología , Taurina/uso terapéuticoRESUMEN
Psoriasis is a chronic skin auto-inflammatory and systemic disorder. Novel treatments are needed to solve a plethora of cases refractory to current treatment regimens. N-bromotaurine (TauNH-Br), a natural taurine oxidizing derivative produced by inflammatory cells, has anti-inflammatory, antiproliferative, and antimicrobial properties. This evidence prompted us to use TauNH-Br as a local agent for treatment of therapy-refractory psoriasis. Two pustular-plaque psoriasis cases, unresponsive to systemic and local treatments, one with localized lesions and one with generalized lesions, were selected. Both applications primarily indicated a sufficient curative activity of 1% TauNH-Br in psoriasis lesions. Moreover, TauNH-Br co-administration with taurine and a novel olive oil formulation cut in half the time needed for TauNH-Br alone to cause the same regression of equivalent psoriasis plaque lesions in the same patient. Importantly, all adverse effects of TauNH-Br (erythema, itching, bleeding) could be minimized by the combination therapy. Periods of 2-7 weeks to achieve almost complete regression with this formulation were remarkably short as compared to conventional treatment regimens that both patients had followed previously. Of note, there was no relapse within 3 months of monitoring. Combination formulations containing TauNH-Br and olive oil could become an advantageous topical medication for treatment of psoriasis.
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Exantema , Psoriasis , Administración Tópica , Humanos , Aceite de Oliva/uso terapéutico , Psoriasis/tratamiento farmacológico , Taurina/análogos & derivados , Taurina/farmacología , Taurina/uso terapéuticoRESUMEN
The current severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic warrants an imperative necessity for effective and safe vaccination, to restrain Coronavirus disease 2019 (COVID-19) including transmissibility, morbidity, and mortality. In this regard, intensive medical and biological research leading to the development of an arsenal of vaccines, albeit incomplete preconditioned evaluation, due to emergency. The subsequent scientific gap raises some concerns in the medical community and the general public. More specifically, the accelerated vaccine development downgraded the value of necessary pre-clinical studies to elicit medium- and long-term beneficial or harmful consequences. Previous experience and pathophysiological background of coronaviruses' infections and vaccine technologies, combined with the global vaccines' application, underlined the obligation of a cautious and qualitative approach, to illuminate potential vaccination-related adverse events. Moreover, the high SARS-CoV-2 mutation potential and the already aggregated genetical alterations provoke a rational vagueness and uncertainty concerning vaccines' efficacy against dominant strains and the respective clinical immunity. This review critically summarizes existing evidence and queries regarding SARS-CoV-2 vaccines, to motivate scientists' and clinicians' interest for an optimal, individualized, and holistic management of this unprecedented pandemic.
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Vacunas contra la COVID-19/uso terapéutico , COVID-19/prevención & control , Vacuna nCoV-2019 mRNA-1273 , Adyuvantes Inmunológicos/efectos adversos , Enfermedades Autoinmunes/inducido químicamente , Vacuna BNT162 , ChAdOx1 nCoV-19 , Aprobación de Drogas , Evaluación Preclínica de Medicamentos , Juramento Hipocrático , Humanos , Efectos Adversos a Largo Plazo/inducido químicamente , Modelos Animales , Medición de Riesgo , SARS-CoV-2 , Vacunas de Productos Inactivados/uso terapéutico , Vacunas Sintéticas/uso terapéutico , Vacunas de ARNmRESUMEN
Taurine haloamines (N-chlorotaurine, N-bromotaurine) due to their strong antiseptic and anti-inflammatory properties are good candidates for topical application in treatment of skin inflammatory/infectious disorders. Recently, we have demonstrated that more stable N-bromotaurine analogs (N-dibromo-dimethyl taurine, N-monobromo-dimethyl taurine) and bromamine T show strong microbicidal and anti-inflammatory properties at concentrations well tolerated by human cells and tissue. Non-steroidal anti-inflammatory drugs (NSAIDs) with cyclooxygenase (COX) inhibitory activity are commonly used in various inflammatory diseases. However, systemic administration of NSAIDs may result in adverse side effects. For example, the use of ibuprofen in children with varicella is associated with enhanced serum levels of TNF-α and with increased risk of necrotizing soft tissue infections and secondary skin infections caused by invasive streptococci. The aim of this study was to examine combined immunomodulatory effects of bromamines and ibuprofen on J774.A1 macrophages. We have shown that the primary activity of ibuprofen, the inhibition of PGE2 production by activated macrophages was intensified in the presence of bromamines. Most importantly, the stimulatory effect of ibuprofen on production of inflammatory cytokines (TNF-α, IL-6) was inhibited by all tested bromamines. These observations indicate that bromamines may neutralize massive production of TNF-α at sites of inflammation, a side effect of ibuprofen. Therefore, we suggest that systemic administration of ibuprofen (NSAIDs) in treatment of inflammatory/infectious skin diseases should be supported by topical application of bromamines as an adjunctive therapy.
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Antiinflamatorios no Esteroideos/farmacología , Ibuprofeno/farmacología , Macrófagos/efectos de los fármacos , Taurina/análogos & derivados , Línea Celular , Citocinas/metabolismo , Dinoprostona/metabolismo , Humanos , Taurina/farmacologíaRESUMEN
The medicinal properties of Cornus mas L. (=Cornus mascula L.), Cornaceae, are well described in Hippocratian documents, and recent research provides experimental evidence for some of these properties. However, the chemical components of Cornus mas L. that may be of pharmaceutical importance are relatively unstable. In this respect a novel methodology for plant nutrient element extraction that provides favorable conditions for simultaneous stabilization of such fragile and unstable structures has been devised. Using this methodology, medicinal preparations derived from Cornus mas L. fresh fruits, proved to possess significant antimicrobial activity selective against S. aureus and P. aeruginosa. This effect became apparent with the addition of sodium bromide in the extraction procedure and varied with the ion availability during extraction. The identification of novel agents with potent antimicrobial activity against these species is of medical importance to overcome the problem of universal antibiotic resistance.
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Antibacterianos/química , Antibacterianos/farmacología , Cornus/química , Extractos Vegetales/química , Extractos Vegetales/farmacología , Farmacorresistencia Bacteriana/efectos de los fármacos , Extracción Líquido-Líquido , Pruebas de Sensibilidad Microbiana , Pseudomonas aeruginosa/efectos de los fármacos , Staphylococcus aureus/efectos de los fármacosRESUMEN
According to the CDC, both Pfizer and Moderna COVID-19 vaccines contain nucleoside-modified messenger RNA (mRNA) encoding the viral spike glycoprotein of severe acute respiratory syndrome caused by corona virus (SARS-CoV-2), administered via intramuscular injections. Despite their worldwide use, very little is known about how nucleoside modifications in mRNA sequences affect their breakdown, transcription and protein synthesis. It was hoped that resident and circulating immune cells attracted to the injection site make copies of the spike protein while the injected mRNA degrades within a few days. It was also originally estimated that recombinant spike proteins generated by mRNA vaccines would persist in the body for a few weeks. In reality, clinical studies now report that modified SARS-CoV-2 mRNA routinely persist up to a month from injection and can be detected in cardiac and skeletal muscle at sites of inflammation and fibrosis, while the recombinant spike protein may persist a little over half a year in blood. Vaccination with 1-methylΨ (pseudouridine enriched) mRNA can elicit cellular immunity to peptide antigens produced by +1 ribosomal frameshifting in major histocompatibility complex-diverse people. The translation of 1-methylΨ mRNA using liquid chromatography tandem mass spectrometry identified nine peptides derived from the mRNA +1 frame. These products impact on off-target host T cell immunity that include increased production of new B cell antigens with far reaching clinical consequences. As an example, a highly significant increase in heart muscle 18-flourodeoxyglucose uptake was detected in vaccinated patients up to half a year (180 days). This review article focuses on medical biochemistry, proteomics and deutenomics principles that explain the persisting spike phenomenon in circulation with organ-related functional damage even in asymptomatic individuals. Proline and hydroxyproline residues emerge as prominent deuterium (heavy hydrogen) binding sites in structural proteins with robust isotopic stability that resists not only enzymatic breakdown, but virtually all (non)-enzymatic cleavage mechanisms known in chemistry.
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Vacunas contra la COVID-19 , COVID-19 , ARN Mensajero , Glicoproteína de la Espiga del Coronavirus , Humanos , COVID-19/prevención & control , COVID-19/inmunología , Vacunas contra la COVID-19/inmunología , Vacunas de ARNm/inmunología , Seudouridina , Proteínas Recombinantes/administración & dosificación , ARN Viral , Glicoproteína de la Espiga del Coronavirus/inmunología , Glicoproteína de la Espiga del Coronavirus/genética , Vacunación , Vacunas Sintéticas/inmunología , Vacunas Sintéticas/administración & dosificaciónRESUMEN
Human prion protein and prion-like protein misfolding are widely recognized as playing a causal role in many neurodegenerative diseases. Based on in vitro and in vivo experimental evidence relating to prion and prion-like disease, we extrapolate from the compelling evidence that the spike glycoprotein of SARS-CoV-2 contains extended amino acid sequences characteristic of a prion-like protein to infer its potential to cause neurodegenerative disease. We propose that vaccine-induced spike protein synthesis can facilitate the accumulation of toxic prion-like fibrils in neurons. We outline various pathways through which these proteins could be expected to distribute throughout the body. We review both cellular pathologies and the expression of disease that could become more frequent in those who have undergone mRNA vaccination. Specifically, we describe the spike protein's contributions, via its prion-like properties, to neuroinflammation and neurodegenerative diseases; to clotting disorders within the vasculature; to further disease risk due to suppressed prion protein regulation in the context of widely prevalent insulin resistance; and to other health complications. We explain why these prion-like characteristics are more relevant to vaccine-related mRNA-induced spike proteins than natural infection with SARS-CoV-2. We note with an optimism an apparent loss of prion-like properties among the current Omicron variants. We acknowledge that the chain of pathological events described throughout this paper is only hypothetical and not yet verified. We also acknowledge that the evidence we usher in, while grounded in the research literature, is currently largely circumstantial, not direct. Finally, we describe the implications of our findings for the general public, and we briefly discuss public health recommendations we feel need urgent consideration. An earlier version of this article was previously posted to the Authorea preprint server on August 16, 2022.
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We report on an aggressive, infiltrating, metastatic, and ultimately lethal basaloid type of carcinoma arising shortly after an mRNA vaccination for COVID-19. The wife of the patient, since deceased, gave the consent for publishing the case. The malignancy was of cutaneous origin and the case showed symptoms consistent with Bell's palsy and trigeminal neuralgia beginning four days post-vaccination (right side head temporal pain). The temporal pain was suggestive for inflammation and impairment of T cell immune activation. Magnetic Resonance Imaging (MRI) showed a vascular loop on the left lateral aspect of the 5th cranial root exit of cerebellopontine angle constituting presumably a normal variant and was considered as an unrelated factor to the right-sided palsy and pain symptoms that corresponded to cranial nerves V (trigeminal nerve) and VII (facial nerve). In this study we describe all aspects of this case and discuss possible causal links between the rapid emergence of this metastatic cancer and mRNA vaccination. We place this within the context of multiple immune impairments potentially related to the mRNA injections that would be expected to potentiate more aggressive presentation and progression of cancer. The type of malignancy we describe suggests a population risk for occurrence of a large variety of relatively common basaloid phenotype cancer cells, which may have the potential for metastatic disease. This can be avoidable with early diagnosis and adequate treatment. Since facial paralysis/pain is one of the more common adverse neurological events following mRNA injection, careful inspection of cutaneous/soft tissue should be conducted to rule out malignancy. An extensive literature review is carried out, in order to elucidate the toxicity of mRNA vaccination that may have led to the death of this patient. Preventive and precise routine clinical investigations can potentially avoid future mortalities. See also Figure 1(Fig. 1).
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As a result of the spread of SARS-CoV-2, a global pandemic was declared. Indiscriminate COVID-19 vaccination has been extended to include age groups and naturally immune people with minimal danger of suffering serious complications due to COVID-19. Solid immuno-histopathological evidence demonstrates that the COVID-19 genetic vaccines can display a wide distribution within the body, affecting tissues that are terminally differentiated and far away from the injection site. These include the heart and brain, which may incur in situ production of spike protein eliciting a strong autoimmunological inflammatory response. Due to the fact that every human cell which synthesises non-self antigens, inevitably becomes the target of the immune system, and since the human body is not a strictly compartmentalised system, accurate pharmacokinetic and pharmacodynamic studies are needed in order to determine precisely which tissues can be harmed. Therefore, our article aims to draw the attention of the scientific and regulatory communities to the critical need for biodistribution studies for the genetic vaccines against COVID-19, as well as for rational harm-benefit assessments by age group.
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Vacunas contra la COVID-19 , COVID-19 , Humanos , Vacunas contra la COVID-19/efectos adversos , COVID-19/prevención & control , Distribución Tisular , SARS-CoV-2 , EncéfaloRESUMEN
The mRNA SARS-CoV-2 vaccines were brought to market in response to the public health crises of Covid-19. The utilization of mRNA vaccines in the context of infectious disease has no precedent. The many alterations in the vaccine mRNA hide the mRNA from cellular defenses and promote a longer biological half-life and high production of spike protein. However, the immune response to the vaccine is very different from that to a SARS-CoV-2 infection. In this paper, we present evidence that vaccination induces a profound impairment in type I interferon signaling, which has diverse adverse consequences to human health. Immune cells that have taken up the vaccine nanoparticles release into circulation large numbers of exosomes containing spike protein along with critical microRNAs that induce a signaling response in recipient cells at distant sites. We also identify potential profound disturbances in regulatory control of protein synthesis and cancer surveillance. These disturbances potentially have a causal link to neurodegenerative disease, myocarditis, immune thrombocytopenia, Bell's palsy, liver disease, impaired adaptive immunity, impaired DNA damage response and tumorigenesis. We show evidence from the VAERS database supporting our hypothesis. We believe a comprehensive risk/benefit assessment of the mRNA vaccines questions them as positive contributors to public health.
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COVID-19 , Exosomas , G-Cuádruplex , Inmunidad Innata , MicroARNs , Enfermedades Neurodegenerativas , Vacunas Sintéticas , Vacunas de ARNm , COVID-19/prevención & control , Vacunas contra la COVID-19/efectos adversos , Exosomas/metabolismo , Humanos , MicroARNs/genética , MicroARNs/metabolismo , Enfermedades Neurodegenerativas/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismo , SARS-CoV-2 , Glicoproteína de la Espiga del Coronavirus , Vacunación/efectos adversos , Vacunas Sintéticas/efectos adversos , Vacunas de ARNm/efectos adversosRESUMEN
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein and prions use common pathogenic pathways to induce toxicity in neurons. Infectious prions rapidly activate the p38 mitogen activated protein kinase (MAPK) pathway, and SARS-CoV-2 spike proteins rapidly activate both the p38 MAPK and c-Jun NH2-terminal kinase (JNK) pathways through toll-like receptor signaling, indicating the potential for similar neurotoxicity, causing prion and prion-like disease. In this review, we analyze the roles of autophagy inhibition, molecular mimicry, elevated intracellular p53 levels and reduced Wild-type p53-induced phosphatase 1 (Wip1) and dual-specificity phosphatase (DUSP) expression in neurons in the disease process. The pathways induced by the spike protein via toll-like receptor activation induce both the upregulation of PrPC (the normal isoform of the prion protein, PrP) and the expression of ß amyloid. Through the spike-protein-dependent elevation of p53 levels via ß amyloid metabolism, increased PrPC expression can lead to PrP misfolding and impaired autophagy, generating prion disease. We conclude that, according to the age of the spike protein-exposed patient and the state of their cellular autophagy activity, excess sustained activity of p53 in neurons may be a catalytic factor in neurodegeneration. An autoimmune reaction via molecular mimicry likely also contributes to neurological symptoms. Overall results suggest that neurodegeneration is in part due to the intensity and duration of spike protein exposure, patient advanced age, cellular autophagy activity, and activation, function and regulation of p53. Finally, the neurologically damaging effects can be cumulatively spike-protein dependent, whether exposure is by natural infection or, more substantially, by repeated mRNA vaccination.
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The structure of synthetic mRNAs as used in vaccination against cancer and infectious diseases contain specifically designed caps followed by sequences of the 5' untranslated repeats of ß-globin gene. The strategy for successful design of synthetic mRNAs by chemically modifying their caps aims to increase resistance to the enzymatic deccapping complex, offer a higher affinity for binding to the eukaryotic translation initiation factor 4E (elF4E) protein and enforce increased translation of their encoded proteins. However, the cellular homeostasis is finely balanced and obeys to specific laws of thermodynamics conferring balance between complexity and growth rate in evolution. An overwhelming and forced translation even under alarming conditions of the cell during a concurrent viral infection, or when molecular pathways are trying to circumvent precursor events that lead to autoimmunity and cancer, may cause the recipient cells to ignore their differential sensitivities which are essential for keeping normal conditions. The elF4E which is a powerful RNA regulon and a potent oncogene governing cell cycle progression and proliferation at a post-transcriptional level, may then be a great contributor to disease development. The mechanistic target of rapamycin (mTOR) axis manly inhibits the elF4E to proceed with mRNA translation but disturbance in fine balances between mTOR and elF4E action may provide a premature step towards oncogenesis, ignite pre-causal mechanisms of immune deregulation and cause maturation (aging) defects.
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Taurine is a fundamental mediator of homeostasis that exerts multiple roles to confer protection against oxidant stress. The development of hypertension, muscle/neuroâassociated disorders, hepatic cirrhosis, cardiac dysfunction and ischemia/reperfusion are examples of some injuries that are linked with oxidative stress. The present review gives a comprehensive description of all the underlying mechanisms of taurine, with the aim to explain its antioxidant actions. Taurine is regarded as a cytoprotective molecule due to its ability to sustain normal electron transport chain, maintain glutathione stores, upregulate antioxidant responses, increase membrane stability, eliminate inflammation and prevent calcium accumulation. In parallel, the synergistic effect of taurine with other potential therapeutic modalities in multiple disorders are highlighted. Apart from the results derived from research findings, the current review bridges the gap between bench and bedside, providing mechanistic insights into the biological activity of taurine that supports its potential therapeutic efficacy in clinic. In the future, further clinical studies are required to support the ameliorative effect of taurine against oxidative stress.
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Antioxidantes/farmacología , Estrés Oxidativo/efectos de los fármacos , Taurina/farmacología , Animales , Antioxidantes/fisiología , Antioxidantes/uso terapéutico , Cardiopatías/tratamiento farmacológico , Homeostasis/efectos de los fármacos , Homeostasis/fisiología , Humanos , Hepatopatías/tratamiento farmacológico , Enfermedades Musculares/tratamiento farmacológico , Enfermedades del Sistema Nervioso/tratamiento farmacológico , Taurina/fisiología , Taurina/uso terapéuticoRESUMEN
To develop novel therapeutic methods for both diabetic and renal disorders, scientists had initially focused on elucidating the molecular mechanisms of taurine in established cell lines and mouse models. Although a large amount of data have been revealed, taurine has been confirmed to be the next step of novel promising therapeutic interventions against diabetic disorders. Taurine appears to ameliorate diabetes 1-related complications in various organs through its antioxidant, anti-inflammatory and anti-hormonal actions. In type 2 diabetes, taurine has been positively implicated in glucose homeostasis, exerting potent hypoglycemic, anti-obesity, hypotensive and hypolipidemic effects. Of particular interest is that taurine provides protection against renal dysfunction, including hypertension and proteinuria, specific glomerular and tubular disorders, acute and chronic renal conditions, and diabetic nephropathy. The ameliorative effects of taurine against renal disorders are based on its osmoregulatory properties, its association with signaling pathways and its association with the renin-angiotensin-aldosterone system (RAAS). Further clinical studies are required to ensure the importance of research findings.
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BACKGROUND: Taurine (Tau) ameliorates cancer pathogenesis. Researchers have focused on the functional properties of bromamine T (BAT), a stable active bromine molecule. Both N-bromotaurine (TauNHBr) and BAT exert potent anti-inflammatory properties, but the landscape remains obscure concerning the anti-cancer effect of BAT. METHODS: We used Crystal Violet, colony formation, flow cytometry and Western blot experiments to evaluate the effect of BAT and Tau on the apoptosis and autophagy of cancer cells. Xenograft experiments were used to determine the in vivo cytotoxicity of either agent. RESULTS: We demonstrated that both BAT and Tau inhibited the growth of human colon, breast, cervical and skin cancer cell lines. Among them, BAT exerted the greatest cytotoxic effect on both RKO and MDA-MB-468 cells. In particular, BAT increased the phosphorylation of c-Jun N-terminal kinases (JNK½), p38 mitogen-activated protein kinase (MAPK), and extracellular-signal-regulated kinases (ERK½), thereby inducing mitochondrial apoptosis and autophagy in RKO cells. In contrast, Tau exerted its cytotoxic effect by upregulating JNK½ forms, thus triggering mitochondrial apoptosis in RKO cells. Accordingly, colon cancer growth was impaired in vivo. CONCLUSIONS: BAT and Tau exerted their anti-tumor properties through the induction of (i) mitochondrial apoptosis, (ii) the MAPK family, and iii) autophagy, providing novel anti-cancer therapeutic modalities.
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Inflammation is the most common cause of most acute and chronic debilitating diseases. Towards unveiling novel therapeutic options for patients with such complications, Nbromotaurine (TauNHBr) has emerged as a potential antiinflammatory agent; however, its therapeutic efficacy is hindered due to its relatively poor stability. To address this challenge, the present study focused on examining the effects of a stable active bromine compound, named bromamine T (BAT). The present study examined the protective properties of BAT against lipopolysaccharide (LPS)mediated inflammation in vitro, by using LPSstimulated murine J774.A1 macrophages (Mφs), as well as in vivo, by using a murine LPSmediated airpouch model. Additionally, its efficacy was compared with that of taurine, a known potent antiinflammatory molecule. In LPSstimulated J774A.1 Mφs, BAT and taurine were very effective in reducing the secretion of proinflammatory mediators. The in vitro experiments indicated that LPSmediated inflammation was attenuated due to the protective properties of BAT and of taurine, probably through the inhibition of phosphorylated p65 NFκB subunit (Ser 536) nuclear translocation. The in vivo experiments also revealed that BAT and taurine inhibited LPSmediated inflammation by reducing total cell/polymorphonuclear cell (PMN) infiltration in the airpouch and by decreasing pouch wall thickness. The analysis of exudates obtained from pouches highlighted that the inhibitory effects of BAT and taurine on the secretion of proinflammatory cytokines were similar to those observed in vitro. Notably, the effect of BAT at the highest concentration tested was superior to that of taurine at the highest concentration. Taken together, the findings of the present study indicate that BAT prevents the LPSinduced inflammatory response both in vitro and in vivo.
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Bromo/uso terapéutico , Inflamación/tratamiento farmacológico , Sulfonamidas/uso terapéutico , Animales , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , Bromo/farmacología , Línea Celular , Núcleo Celular/efectos de los fármacos , Núcleo Celular/metabolismo , Modelos Animales de Enfermedad , Regulación de la Expresión Génica/efectos de los fármacos , Inflamación/patología , Mediadores de Inflamación/metabolismo , Lipopolisacáridos , Ratones Endogámicos C57BL , Fosforilación/efectos de los fármacos , Transporte de Proteínas/efectos de los fármacos , ARN Mensajero/genética , ARN Mensajero/metabolismo , Sulfonamidas/farmacología , Taurina/farmacología , Factor de Transcripción ReIA/metabolismo , Transcripción Genética/efectos de los fármacosRESUMEN
For one century, taurine is considered as an end product of sulfur metabolism. In this review, we discuss the beneficial effect of taurine, its haloamines and taurine upregulated gene 1 (TUG1) long noncoding RNA (lncRNA) in both cancer and inflammation. We outline how taurine or its haloamines (NBromotaurine or NChlorotaurine) can induce robust and efficient responses against inflammatory diseases, providing insight into their molecular mechanisms. We also provide information about the use of taurine as a therapeutic approach to cancer. Taurine can be combined with other chemotherapeutic drugs, not only mediating durable responses in various malignancies, but also circumventing the limitations met from chemotherapeutic drugs, thus improving the therapeutic outcome. Interestingly, the lncRNA TUG1 is regarded as a promising therapeutic approach, which can overcome acquired resistance of cancer cells to selected strategies. In this regard, we can translate basic knowledge about taurine and its TUG1 lncRNA into potential therapeutic options directed against specific oncogenic signaling targets, thereby bridging the gap between bench and bedside.
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Inflamación/genética , Neoplasias/genética , ARN Largo no Codificante/metabolismo , Taurina/análogos & derivados , Animales , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Proliferación Celular/efectos de los fármacos , Proliferación Celular/genética , Modelos Animales de Enfermedad , Progresión de la Enfermedad , Resistencia a Antineoplásicos/genética , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Regulación Neoplásica de la Expresión Génica/inmunología , Humanos , Inflamación/tratamiento farmacológico , Inflamación/inmunología , Inflamación/metabolismo , Neoplasias/tratamiento farmacológico , Neoplasias/inmunología , Neoplasias/metabolismo , Pronóstico , Taurina/metabolismo , Taurina/farmacología , Taurina/uso terapéuticoRESUMEN
Coronaviruses, members of Coronaviridae family, cause extensive epidemics of vast diseases like severe acute respiratory syndrome (SARS) and Coronavirus Disease-19 (COVID-19) in animals and humans. Super spread events (SSEs) potentiate early outbreak of the disease and its constant spread in later stages. Viral recombination events within species and across hosts lead to natural selection based on advanced infectivity and resistance. In this review, the importance of containment of SSEs was investigated with emphasis on stopping COVID-19 spread and its socio-economic consequences. A comprehensive search was conducted among literature available in multiple electronic sources to find articles that addressed the "potential role of SSEs on severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) pandemic" and were published before 20th of August 2020. Overall, ninety-eight articles were found eligible and reviewed. Specific screening strategies within potential super spreading host groups can also help to efficiently manage severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) epidemics, in contrast to the partially effective general restriction measures. The effect of SSEs on previous SARS epidemics has been documented in detail. However, the respective potential impact of SSEs on SARS-COV-2 outbreak is composed and presented in the current review, thereby implying the warranted effort required for effective SSE preventive strategies, which may lead to overt global community health benefits. This is crucial for SARS-COV-2 pandemic containment as the vaccine(s) development process will take considerable time to safely establish its potential usefulness for future clinical usage.
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Microbial species can act in synergy to circumvent environmental stress conditions and survive. In addition, biofilms are a serious public-health issue globally and constitute a clinical emergency. Infection persistence, increased morbidity and mortality, and antibiotic resistance are consequences of poly-microbial synergy. Due to inherited complexity and synergy between numerous species, newer antimicrobial agents of increased efficacy and tolerability are needed. In this unique medical case, a chronic (9 year) multi-bacterial scalp infection was differentially diagnosed from other inflammatory skin disorders by prolonged microbiological culture. The bacterial species found seem to have caused lesions of visible biofilm not documented previously in the medical literature. This complicated infection was treated successfully and rapidly with the combined topical application of the active halogen compounds N-chlorotaurine, N-bromotaurine and bromamine T, which is in contrast to the previous failed systemic and topical therapeutic approaches. This study strengthens the case for the use of active halogen compounds against multi-bacterial infections of the skin in the future, without the occurrence of resistance.