Notes

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Importantly, we also highlight the possible application of various therapeutic strategies including small interfering RNA, CRISPR-Cas9, antisense oligonucleotides, locked nucleic acid Gapmers, small molecules, aptamers, lncRNA promoter to target the lncRNA as a novel and viable options for treatment of PDAC.Strong evidence points to Porphyromonas gingivalis, a Gram-negative anaerobic bacterium, as a keystone species in the development of the chronic form of periodontitis. The aim of the present study was to investigate the ability of highbush blueberry proanthocyanidins (PACs) to alleviate the P. gingivalis-induced deleterious effects on oral mucosal cells. We first showed that highbush blueberry PACs protect the integrity of the gingival keratinocyte barrier against P. gingivalis-mediated damage, as determined by measuring the transepithelial electrical resistance and paracellular flux of FITC-conjugated dextran. Moreover, the PACs prevented the translocation of P. gingivalis across the gingival keratinocyte barrier model. see more The proteinase activity of P. gingivalis was inhibited by the PACs suggesting that they may exert beneficial effects by reducing proteolytic degradation of the epithelial tight junctions. Regulation of gingival fibroblast inflammatory reactions may be one of the ways to prevent and control periodontal disease progression and severity. We showed that PACs significantly reduce IL-6 and IL-8 secretion by P. gingivalis-stimulated gingival fibroblasts. The present study showed the capacity of highbush blueberry PACs to protect the integrity of an in vitro model of gingival keratinocyte barrier against P. gingivalis, and to attenuate the secretion of pro-inflammatory cytokines by gingival fibroblasts infected with P. gingivalis. These results suggest beneficial effects of blueberry PACs thus supporting the need for future clinical trials on the potential of these bioactive molecules for periodontal disease prevention and/or treatment.
The COVID-19 pandemic due to SARS-CoV-2 infection can produce Acute Respiratory Distress Syndrome as a result of a pulmonary cytokine storm. Antihistamines are safe and effective treatments for reducing inflammation and cytokine release. Combinations of Histamine-1 and Histamine-2 receptor antagonists have been effective in urticaria, and might reduce the histamine-mediated pulmonary cytokine storm in COVID-19. Can a combination of Histamine-1 and Histamine-2 receptor blockers improve COVID-19 inpatient outcomes?

A physician-sponsored cohort study of cetirizine and famotidine was performed in hospitalized patients with severe to critical pulmonary symptoms. Pulmonologists led the inpatient care in a single medical center of 110 high-acuity patients that were treated with cetirizine 10mgb.i.d. and famotidine 20mgb.i.d. plus standard-of-care.

Of all patients, including those with Do Not Resuscitate directives, receiving the dual-histamine receptor blockade for at least 48h, the combination drug treatment tamine-mediated cytokine storm. Further clinical studies in COVID-19 are warranted of the repurposed off-label combination of two historically-safe histamine receptor blockers.Epidemiological and experimental animal studies indicate that there is a high risk for the incidence of neuropsychiatric disorders suffering from cardiovascular diseases such as myocardial infarction (MI). However, the potential mechanism of this association remains largely unknown. This study sought to evaluate whether epigenetic alterations in the hippocampus is associated with MI-induced anxiety-like behavior in rats. MI was induced by occlusion of the left anterior descending artery in adult female rats. Anxiety-like behavior was examined by elevated plus maze, light-dark box, and open field test. Relative gene and protein levels expression in the hippocampus were tested by qRT-PCR and western blotting, respectively. We found that MI rats exhibited anxiety-like behavior compared with those in controls, and there is a positive correlation between MI and anxiety-like behavior. We also found that MI decreased KDM6B while increased SIRT1 expression in the hippocampus of MI rats relative to those in controls. In addition, MI not only increased levels of IL-1β, bax, and cleaved-caspase 3, but also increased Iba-1 and GFAP expression in the hippocampus, as compared to those in controls, suggesting a promotion of neuro-inflammation and apoptosis in hippocampus. Co-immunoprecipitation assay illustrated that H3K27me3 functioned by counteracting with YAP activation in the hippocampus of MI rats relative to those in controls. Together, these results suggest a potential role of hippocampal epigenetic signaling in MI-induced anxiety-like behavior in rats, and pharmacological targeting KDM6B or SIRT1 could be a strategy to ameliorate anxiety-like behavior induced by MI.Intracerebral hemorrhage (ICH) is a common neurological disease, causing severe disability and even deaths. Stem cell transplantation has been increasingly used in stroke therapy, and neural stem cells (NSCs) are a good source for stem cell transplantation. However, the regulatory mechanism of NSCs remains unclear. In this study, we examined the impact of insulin-like growth factor-1 (IGF-1) secreted by NSCs on microglial polarization following ICH in adult C57BL/6 mice. Mouse models of ICH were established by collagenase injection. ICH mice received NSC transplantation 1 h after model establishment. Firstly, the changes of microglial polarization in cerebral tissues of ICH mice were detected by immunofluorescence and ELISA. Secondly, the molecular mechanism underlying the microglial polarization was evaluated repeatedly with the application of IGF-1R siRNA and IGF-1R-mediated inhibition. We assessed the brain water content and behavioral deficits of ICH mice 12, 24, 48, and 72 h after surgery. The survival of neurons in the brain was examined using Nissl staining and TUNEL staining at 72 h. The TLR4/NF-κB pathway implicated in ICH-induced inflammation was profiled by Western blot analysis and immunohistochemistry. Finally, the changes in microglia after ICH in mice were re-examined under different doses of rhIGF-1. In summary, NSC transplantation changed microglial polarization in ICH mice. IGF-1R inhibition and knockdown reversed the therapeutic effect of NSCs, and rhIGF-1 had an anti-inflammatory effect. The results of this study suggest that IGF-1R stimulation is a potential target for stem cell-based treatment of cerebral hemorrhage and may attenuate inflammatory response in the brain after bleeding.
In addition to various biological effects of natriuretic peptides (NP) on cardiovascular systems, we recently reported that NP raises intracellular temperature in cultured adipocytes. We herein examined the possible thermogenic action of NP in consideration of hemodynamic parameters and inflammatory reaction by proposing structural equation models.

The study population consisted of 1985 consecutive patients who underwent cardiac catheterization. Covariance structure analyses were performed to clarify the direct contribution of plasma B-type NP (BNP) to body temperature (BT) by excluding other confounding factors. A hierarchical path model showed increase in BNP, increase in C-reactive protein and decrease in left ventricular ejection fraction were mutually associated. As expected, C-reactive protein was positively correlated with BT. Importantly, despite a negative correlation between BNP and left ventricular ejection fraction, a decrease in the left ventricular ejection fraction was associated with BT decrease, whereas elevation in BNP level was associated with BT increase independently of C-reactive protein level (P = .007).

Patients with LV dysfunction tend to manifest a decrease in BT, whereas BNP elevation is associated with an increase in BT independently of inflammatory response. These findings suggest the adaptive heat-retaining property of NP (and/or NP-associated factors) when BT falls owing to unfavorable hemodynamic conditions in a state of impaired cardiac function.
Patients with LV dysfunction tend to manifest a decrease in BT, whereas BNP elevation is associated with an increase in BT independently of inflammatory response. These findings suggest the adaptive heat-retaining property of NP (and/or NP-associated factors) when BT falls owing to unfavorable hemodynamic conditions in a state of impaired cardiac function.
The vitamin D endocrine system may have a variety of actions on cells and tissues involved in COVID-19 progression especially by decreasing the Acute Respiratory Distress Syndrome. Calcifediol can rapidly increase serum 25OHD concentration. We therefore evaluated the effect of calcifediol treatment, on Intensive Care Unit Admission and Mortality rate among Spanish patients hospitalized for COVID-19.

Parallel pilot randomized open label, double-masked clinical trial.

University hospital setting (Reina Sofia University Hospital, Córdoba Spain.) PARTICIPANTS 76 consecutive patients hospitalized with COVID-19 infection, clinical picture of acute respiratory infection, confirmed by a radiographic pattern of viral pneumonia and by a positive SARS-CoV-2 PCR with CURB65 severity scale (recommending hospital admission in case of total score > 1).

All hospitalized patients received as best available therapy the same standard care, (per hospital protocol), of a combination of hydroxychloroquine (400 mg every disease, but larger trials with groups properly matched will be required to show a definitive answer.Cordia verbenacea DC is a plant whose geographical distribution is all over Brazil, but mainly on the country's coastal areas. It is used by folk medicine to treat inflammations and chronic pain with application of the raw extract of macerated leaves in the region of pain. This paper aims to provide an integrative review of the role of chemical compounds present in the extract and the essential oil of Cordia verbenacea DC for their anti-inflammatory, antimicrobial and healing properties. The extract of Cordia verbenacea DC is widely found within popular culture as teas, decoctions, infusions, pomades/creams for anti-inflammatory, antimicrobial and healing uses. Its extract is mainly composed of α-humulene, α-pinene, trans-caryophyllene, artemetin, spathulenol and allo-aromadrendene. The described effects of the chemical compounds found in the extract are applied to muscle bruising and myofascial pain, edema reduction and chronic tendonitis, when used topically (with a comercial product being marketed); and tonservation, safe management of the species, use of the extract/essential oil and development of plant-based products.
The genus Melastoma consists of approximately 100 species distributed widely in tropical and subtropical countries, and Melastoma species are often used for medicinal purposes, such as treatment for bleeding, diarrhea, diabetes, and gynecological tumors by local people, mostly in Southeast Asian countries.

The present review summarizes the traditional uses, phytochemistry and pharmacology of species belonging to Melastoma to suggest further research strategies and to facilitate the exploitation of the therapeutic potential of Melastoma species for the treatment of human disorders.

Information related to the traditional uses, phytochemistry and pharmacological activities was systematically collected by searching for the word "Melastoma" in electronic databases, including SciFinder, Web of Science, PubMed, and Google Scholar, from Apr. 1968 until Dec. 2019.

A systematic literature survey revealed that Melastoma spp. are widely distributed in southern Asia to northern Oceania and the Pacific Islands and are traditionally used to treat bleeding, diarrhea, swelling, and gynecological tumors.
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