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Abildtrup Alexandersen posted an update a month ago
Independent of BMI, higher insulin resistance was associated with a downregulation of duodenal DEGs mainly related to the immune system, inflammation, and xenobiotic metabolism. Also, intestinal lipoprotein metabolism may have a certain relevance in the regulation of insulin resistance in nonobese women.
Independent of BMI, higher insulin resistance was associated with a downregulation of duodenal DEGs mainly related to the immune system, inflammation, and xenobiotic metabolism. Also, intestinal lipoprotein metabolism may have a certain relevance in the regulation of insulin resistance in nonobese women.
Dental caries is an infectious disease with predominantly of cariogenic bacteria such as Streptococcus mutans (S mutans). Xylitol is considered as one of the effective agents that can limit this dental infection. In this randomised, placebo-controlled trial, we aimed to evaluate the potential reflection of short-term xylitol consumption on pro-inflammatory cytokines (TNF-α, IL-6 and IL-8) and S mutans counts by ELISA and qPCR (Quantitative real-time PCR), respectively.
In this study, 154 participants were assigned to two groups, control and xylitol. Dental examination, saliva and swab samples were done at baseline and at 3-week for clinical and microbiological assessment.
In xylitol group at the end of 3-week, gingival and plaque index scores were significantly decreased with respect to baseline values (P<.001 and P<.05, respectively). The salivary concentration of TNF-α, IL-6 and IL-8 were statistically declined at 3-week, more so than those at baseline in xylitol group (P<.001). S mutans expression was reduced about fivefold at 3-week use of xylitol and it was a statistically significant difference compared to baseline (P<.001).
Intriguingly, even short-term consumption of xylitol might play a favourable role in maintaining the oral health status, possibly as a result of decreasing the release of pro-inflammatory cytokines and the counts of S mutans. Nonetheless, this investigation warrants further endorsement.
Intriguingly, even short-term consumption of xylitol might play a favourable role in maintaining the oral health status, possibly as a result of decreasing the release of pro-inflammatory cytokines and the counts of S mutans. Nonetheless, this investigation warrants further endorsement.
Spinocerebellar ataxia type 3 (SCA3) is a hereditary neurodegenerative disorder with high clinical heterogeneity. Twin study is valuable to estimate the contributions of gene and/or environment to phenotypic variance. However, SCA3 twins were extremely sparse and rarely reported.
A pair of monozygotic twins with SCA3 was assessed using well-acknowledged scales. Genetic modifiers and methylation levels were determined by Sanger sequencing and pyrosequencing.
Sharing identical CAG repeat lengths, the twins presented with similar symptoms, whereas, the younger sister had an earlier age at onset of two years. The occurrence time and severity of constipation, blepharospasm and fasciculation were markedly different between the twins. Notable methylation level differences of several CpG sites existed between the twins.
It is the first time to report SCA3 monozygotic twin worldwide. The role of epigenetic factors in the phenotype variance deserved more attention. The DNA methylation may influence the phenotypic variance by altering the occurrence time and severity of symptoms, indicating its potential in alleviating the disease.
It is the first time to report SCA3 monozygotic twin worldwide. The role of epigenetic factors in the phenotype variance deserved more attention. The DNA methylation may influence the phenotypic variance by altering the occurrence time and severity of symptoms, indicating its potential in alleviating the disease.Chagas disease affects 6-8 million people worldwide, remaining a public health concern. Toxicity, several adverse effects and inefficiency in the chronic stage of the disease are the major challenges regarding the available treatment protocols. This work involved the synthesis of twenty-two 1,4-disubstituted-1,2,3-triazole analogues of benznidazole (BZN), by using a click chemistry strategy. Analogues were obtained in moderate to good yields (40-97 %). Antitrypanosomal activity was evaluated against the amastigote forms of Trypanosoma cruzi. Compound 8 a (4-(2-nitro-1H-imidazol-1-yl)methyl)-1-phenyl-1H-1,2,3-triazole) without substituents on phenyl ring showed similar biological activity to BZN (IC50 =3.0 μM, SI>65.3), with an IC50 =3.1 μM and SI>64.5. Compound 8 o (3,4-di-OCH3 -Ph) with IC50 = 0.65 μM was five-fold more active than BZN, and showed an excellent selectivity index (SI>307.7). Compound 8 v (3-NO2 , 4-CH3 -Ph) with IC50 =1.2 μM and relevant SI>166.7, also exhibited higher activity than BZN. SAR analysis exhibited a pattern regarding antitrypanosomal activity relative to BZN, in compounds with electron-withdrawing groups (Hammett σ+) at position 3, and electron-donating groups (Hammett σ-) at position 4, as observed in 8 o and 8 v. Further research might explore in vivo antitrypanosomal activity of promising analogues 8 a, 8 o, and 8 v. Overall, this study indicates that approaches such as the bioisosteric replacement of amide group by 1,2,3-triazole ring, the use of click chemistry as a synthesis strategy, and design tools like Craig-plot and Topliss tree are promising alternatives to drug discovery.
Glioblastoma (GBM) is a highly aggressive primary brain tumor. Currently, the suggested line of action is the surgical resection followed by radiotherapy and treatment with the adjuvant temozolomide, a DNA alkylating agent. However, the ability of tumor cells to deeply infiltrate the surrounding tissue makes complete resection quite impossible, and, in consequence, the probability of tumor recurrence is high, and the prognosis is not positive. selleck GBM is highly heterogeneous and adapts to treatment in most individuals. Nevertheless, these mechanisms of adaption are unknown.
In this review, we will discuss the recent discoveries in molecular and cellular heterogeneity, mechanisms of therapeutic resistance, and new technological approaches to identify new treatments for GBM. The combination of biology and computer resources allow the use of algorithms to apply artificial intelligence and machine learning approaches to identify potential therapeutic pathways and to identify new drug candidates.
These new approaches will generate a better understanding of GBM pathogenesis and will result in novel treatments to reduce or block the devastating consequences of brain cancers.