RESUMO

Communication between neighboring or distant cells is made through a complex network that includes extracellular vesicles (EVs). Exosomes, which are a subgroup of EVs, are released from most cell types and have been found in biological fluids such as urine, plasma, and airway secretions like bronchoalveolar lavage (BAL), nasal lavage, saliva, and sputum. Mainly, the cargo exosomes are enriched with mRNAs and microRNAs (miRNAs), which can be transferred to a recipient cell consequently modifying and redirecting its biological function. The effects of miRNAs derive from their role as gene expression regulators by repressing or degrading their target mRNAs. Nowadays, various types of research are focused on evaluating the potential of exosomal miRNAs as biomarkers for the prognosis and diagnosis of different pathologies. Nevertheless, there are few reports on their role in the pathophysiology of idiopathic pulmonary fibrosis (IPF), a chronic lung disease characterized by progressive lung scarring with no cure. In this review, we focus on the role and effect of exosomal miRNAs as intercellular communicators in the onset and progression of IPF, as well as discussing their potential utility as therapeutic agents for the treatment of this disease.

Assuntos

RESUMO

The SARS-CoV-2 pandemic has confirmed the apocalyptic predictions that virologists have been making for several decades. The challenge the world is facing is that of trying to find a possible treatment, and a viable and expedient option for addressing this challenge is the repurposing of drugs. However, in some cases, although these drugs are approved for use in humans, the mechanisms of action involved are unknown. In this sense, to justify its therapeutic application to a new disease, it is ideal, but not necessary, to know the basic mechanisms of action involved in a drug's biological effects. This review compiled the available information regarding the various effects attributed to Ivermectin. The controversy over its use for the treatment of COVID-19 is demonstrated by this report that considers the proposal unfeasible because the therapeutic doses proposed to achieve this effect cannot be achieved. However, due to the urgent need to find a treatment, an exhaustive and impartial review is necessary in order to integrate the knowledge that exists, to date, of the possible mechanisms through which the treatment may be helpful in defining safe doses and schedules of Ivermectin.

RESUMO

Background: Infection by SARS-CoV-2 has been associated with multiple symptoms; however, still, little is known about persistent symptoms and their probable association with the risk of developing pulmonary fibrosis in patients post-COVID-19. Methods: A longitudinal prospective study on health workers infected by SARS-CoV-2 was conducted. In this work, signs and symptoms were recorded of 149 health workers with a positive PCR test for SARS-CoV-2 at the beginning of the diagnosis, during the active infection, and during post-COVID-19 follow-up. The McNemar chi-square test was used to compare the proportions and percentages of symptoms between the baseline and each follow-up period. Results: The signs and symptoms after follow-up were cardiorespiratory, neurological, and inflammatory. Gastrointestinal symptoms were unusual at the disease onset, but unexpectedly, their frequency was higher in the post-infection stage. The multivariate analysis showed that pneumonia (HR 2.4, IC95%: 1.5−3.8, p < 0.001) and positive PCR tests still after four weeks (HR 5.3, IC95%: 2.3-12.3, p < 0.001) were factors associated with the diagnosis of post-COVID-19 pulmonary fibrosis in this study group. Conclusions: Our results showed that pneumonia and virus infection persistence were risk factors for developing pulmonary fibrosis post-COVID-19, after months of initial infection.

Assuntos

RESUMO

Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive disease with high mortality and unclear etiology. Previous evidence supports that the origin of this disease is associated with epigenetic alterations, age, and environmental factors. IPF initiates with chronic epithelial lung injuries, followed by basal membrane destruction, which promotes the activation of myofibroblasts and excessive synthesis of extracellular matrix (ECM) proteins, as well as epithelial-mesenchymal transition (EMT). Due to miRNAs' role as regulators of apoptosis, proliferation, differentiation, and cell-cell interaction processes, some studies have involved miRNAs in the biogenesis and progression of IPF. In this context, the analysis and discussion of the probable association of miRNAs with the signaling pathways involved in the development of IPF would improve our knowledge of the associated molecular mechanisms, thereby facilitating its evaluation as a therapeutic target for this severe lung disease. In this work, the most recent publications evaluating the role of miRNAs as regulators or activators of signal pathways associated with the pathogenesis of IPF were analyzed. The search in Pubmed was made using the following terms: "miRNAs and idiopathic pulmonary fibrosis (IPF)"; "miRNAs and IPF and signaling pathways (SP)"; and "miRNAs and IPF and SP and IPF pathogenesis". Additionally, we focus mainly on those works where the signaling pathways involved with EMT, fibroblast differentiation, and synthesis of ECM components were assessed. Finally, the importance and significance of miRNAs as potential therapeutic or diagnostic tools for the treatment of IPF are discussed.

Assuntos

RESUMO

Salvia amarissima Ortega is an endemic species of Mexico used in folk medicine to alleviate pain and as a nervous tranquilizer. The S. amarissima extract and one of its abundant metabolites, identified and isolated through chromatographic techniques, were investigated to obtain scientific evidence of its potential effects to relieve nociplastic pain such as fibromyalgia. Then, the extract and amarisolide A (3-300 mg/kg, i.p.) were pharmacologically evaluated in reserpine-induced fibromyalgia-type chronic pain and in depressive-like behavior (as a common comorbidity) by using the forced swimming test in rats. The 5-HT1A serotonin receptor (selective antagonist WAY100635, 1 mg/kg, i.p.) was explored after the prediction of a chemical interaction using in silico analysis to look for a possible mechanism of action of amarisolide A. Both the extract and amarisolide A produced significant and dose-dependent antihyperalgesic and antiallodynic effects in rats, as well as significant antidepressive behavior without sedative effects when the antinociceptive dosages were used. The 5-HT1A serotonin receptor participation was predicted by the in silico descriptors and was corroborated in the presence of WAY100635. In conclusion, S. amarissima possesses antihyperalgesic, antiallodynic, and anti-depressive activities, partially due to the presence of amarisolide A, which involves the 5-HT1A serotonin receptor. This pharmacological evidence suggests that S. amarissima and amarisolide A are both potential alternatives to relieve pain-like fibromyalgia.

RESUMO

Pulmonary hypertension is a rare condition that impairs patients' quality of life and life expectancy. The development of noninvasive instruments may help elucidate the prognosis of this cardiorespiratory disease. We aimed to evaluate the utility of routinely performed noninvasive test results as prognostic markers in patients with pulmonary hypertension. We enrolled 198 patients with mean pulmonary artery pressure >25 mmHg measured at cardiac catheterisation or echocardiographic pulmonary artery systolic pressure > 40 mmHg and tricuspid regurgitation Vmax >2.9 m/s, and clinical information regarding management and follow-up studies from the date of diagnosis. Multivariate analysis revealed that female sex [HR: 0.21, (95% CI: 0.07-0.64); p = 0.006], the presence of collagenopathies [HR: 8.63, (95% CI: 2.38-31.32); p = 0.001], an increased red blood cell distribution width [HR: 1.25, (95% CI: 1.04-1.49); p = 0.017] and an increased electrocardiographic P axis (P°)/T axis (T°) ratio [HR: 0.93, (95% CI: 0.88-0.98); p = 0.009] were severity-associated factors, while older age [HR: 1.57, (95% CI: 1.04-1.28); p = 0.006], an increased QRS axis (QRS°)/T° ratio [HR: 1.21, (95% CI: 1.09-1.34); p < 0.001], forced expiratory volume in 1 s [HR: 0.94, (95% CI: 0.91-0.98); p = 0.01] and haematocrit [HR: 0.93, (95% CI: 0.87-0.99); p = 0.04] were mortality-associated factors. Our results support the importance of red blood cell distribution width, electrocardiographic ratios and collagenopathies for assessing pulmonary hypertension prognosis.

RESUMO

Nowadays, glycine is used in nutritional supplements and to attenuate chronic complications of diabetes and obesity; however, its use has side effects as insulin resistance. Our aim was to evaluate the effect of chronic glycine supplementation on insulin, glucose and triglyceride levels in healthy Wistar rats. Groups were: Control (C), that received sterilized water only, glycine (GG), that received 1% glycine and taurine (TG), that received 0.5% taurine during 6 months (n = 10). Our results showed no differences in plasma insulin levels after six months of supplementation (C: 13.22 ± 2.0; GG: 11.4 ± 2.0; TG: 11.13 ± 2.0 ng/ml; p = 0.64). Likewise, neither glucose plasma concentration (C: 99.9 ± 3.9 mg/dl; GG: 104.3 ± 4.3 mg/dl; TG: 104.5 ± 4.8 mg/dl) (p = 0.88) nor triglyceride levels (C: 58.4 ± 5.6 mg/dl; GG: 46.9 ± 2.3 mg/dl; TG: 50.68 ± 3.3 mg/dl), showed differences after six months supplementation (p = 0.22). Furthermore, the analysis of glycine (C: 80 ± 24.6; GG: 83.9 ± 25.9; TG: 90.7 ± 13.5 nmol/ml) (p = 0.19) and taurine (C: 169 ± 15.17; GG: 148.7 ± 23.9; TG: 165.8 ± 22.5 nmol/ml) (p = 0.4) in the plasma of animals with supplementation showed no significant changes. Additionally, general urine tests and histological analysis of liver or kidneys showed no alterations. In conclusion, chronic supplementation with 1% glycine did not have any significant detrimental side effects in our model. However, more studies are still necessary to evaluate the effect of 1% glycine supplementation in humans.

Assuntos

RESUMO

Although thiamine pyrophosphate (TPP) is considered a protective agent for endothelial cells, it is still unknown if this is associated with nitric oxide (NO) synthesis. Our aim was to evaluate the synthesis of NO in endothelial cells incubated with TPP and high glucose concentrations. Endothelial cells from the umbilical cord vein from newborns (n = 20), were incubated with 5, 15 or 30 mmol/L glucose, in absence or presence of 0.625 mg/ml of TPP. Our results showed a significant increase in cell proliferation (> 40%; P < 0.05), and cell viability (> 90%; P < 0.001) after 48 h in endothelial cells cultured with glucose plus TPP. Likewise, in the presence of glucose and TPP an important rise in the consumption of glucose by the endothelial cells was observed after 24 h (> 7%; P < 0.001) and 48 h (> 10%; P < 0.05). Additionally, the levels of lactate after incubation with glucose and TPP showed only slight variations after 48 h (P < 0.05). However, these changes were clearly different from those observed in the absence of TPP. Interestingly, we found that the changes mentioned were linked with reduced levels of nitrites both at 24 h (< 171 pmol/µg protein; P < 0.001), and 48 h (< 250 pmol/µg protein; P < 0.05), which was associated with a reduced expression of mRNA of eNOS in endothelial cells incubated with TPP and high glucose. In conclusion, the presence of TPP regulates the consumption of glucose and the synthesis of NO, which would explain its protective effect in the endothelium of diabetic patients.

Assuntos

RESUMO

Demodex folliculorum shows a high occurrence in the general population, however, its pathologic relevance is still controversial. In this prospective study, we evaluated the prevalence of D. folliculorum on eyelashes from 8,033 subjects of a university population (including 7,782 students, and 251 academics). Additional information on some risk factors to infection by the mites was evaluated, as well. A prevalence of 1.47% was found, where 118 individuals were positive for D. folliculorum; and, among them, 63 (53.4%) were women and 55 (46.6%) were men. Results showed a negative correlation with the age (r = -0.45), the highest prevalence was found in individuals between 19 and 22 years of age (2.1%, 84 patients). The number of D. folliculorum mites did not differ between the right and left eye; however, the use of cosmetics or facial cream, contact lens, hair removers, were factors present in patients infected with D. folliculorum. Although Demodex prevalence did not increase in line with weight, we found significantly higher prevalence in the 51-60 kg and 71-80 kg weight groups, and a particularly high prevalence in the over 81 kg weight group (2.6%). In conclusion, it was observed that the main population positive to infection consisted of young adults; this is in contrast with the international evidence reporting a high rate of infection in older adults. Besides, our results suggest that items of daily use such as cosmetics, facial cream, eyeliner, glasses, or contact lenses may be some of the main culprits of the infection by D. folliculorum.

Assuntos

RESUMO

BACKGROUND & AIMS: Adequate nutrition from which amino acids are part gives us protection against infectious or metabolic diseases. In particular, glycine has immunomodulatory properties and is a secretagogue of insulin. However, its absorption rate or plasma levels are impaired in bacterial infection or high glucose levels. The aim of this study was to evaluate the association between glycine and insulin plasma levels in patients with pulmonary tuberculosis (PTB) and type 2 diabetes mellitus (DM2). METHODS: Plasma levels of insulin and glycine were determined in four groups: 1) patients with PTB; 2) patients with PTB-DM2; 3) household contacts with DM2 (C-DM2), and 4) healthy household contacts (H-C). Likewise, we analyzed the plasma levels of glucose, serine, arginine, lysine, taurine, and glutamic acid. RESULTS: We observed significant differences in the glycine levels between PTB and PTB-DM2 vs C-DM2 and H-C groups (P < 0.05). We observed also important differences in insulin and glucose levels after comparisons between PTB, PTB-DM2, and C-DM2 vs. H-C groups (P < 0.05). A correlation between glycine and insulin levels in the PTB (r = 0.326) and PTB-DM2 (r = 0.318) groups was found. CONCLUSION: Our results showed a significant association between glycine and insulin plasma levels in patients with PTB and PTB-DM2, which suggests that the determination of glycine levels could be used as a reference test to evaluate both pathologic conditions. An additional support to the above is that significant changes in the glucose levels in these groups were observed, too.

Assuntos