Pathophysiology最新文献

Small GTP-binding proteins of the Rab family regulate intracellular vesicle trafficking across many aspects of the transport system. Among these, Rab9 is recognized for its role in controlling the transport system not only around the trans-Golgi network but also around the late endosome. However, the specific functions across different cell types and tissues remain unclear. Here, for the first time, we report that Rab9 negatively regulates morphological changes in the FBD-102b cell line, an oligodendroglial precursor cell line undergoing morphological differentiation. The knockdown of Rab9 led to an increase in cell shape alterations characterized by widespread membrane extensions. These changes were accompanied by increased expression levels of oligodendroglial cell differentiation and myelination marker proteins. Notably, the knockdown of Rab9 was capable of recovering defective cell morphological changes induced by tunicamycin, an inducer of endoplasmic reticulum (ER) stress, which is one of the major causes of oligodendroglial cell diseases such as Pelizaeus-Merzbacher disease (PMD, currently known as hypomyelinating leukodystrophy type 1 [HLD1]). In addition, Rab9 knockdown recovered levels of ER stress marker proteins and differentiation markers. Similar results were obtained in the cases of dithiothreitol (DTT), another chemical ER stress inducer, as well as HLD1-associated proteolipid protein 1 (PLP1) mutant protein. These results indicate a unique role for Rab9 in oligodendroglial cell morphological changes, suggesting its potential as a therapeutic target for mitigating diseases such as HLD1 at the molecular and cellular levels.

The present study aims to evaluate the effect of Sepia pharaonis ink on insulin resistance in PCOS-induced mice. Treatment with sepia ink in dehydroepiandrosterone (DHEA)-induced PCOS mice at various doses of 50 mg/kg, 100 mg/kg, and 200 mg/kg body weight mitigated the insulin resistance in the study groups with decreased concentration of testosterone and increased concentrations of estrogen and progesterone compared to the PCOS group tested by ELISA. The histopathological analysis and restoration of glucose analysis showed a significant reduction in treatment groups. Reduced expression of insulin resistance genes like androgen receptor (AR), insulin receptor substrate 1 (IRS-1), and insulin-like growth factor1 (IGF-1) by qRT-PCR indicate a positive impact of sepia ink in alleviating the symptoms associated with PCOS. Taken together, the results of this study indicate sepia ink as a promising therapeutic intervention and a possible drug target for insulin resistance in diabetes and gynecological disorders like PCOS.

Background: Surgeons often encounter patients with intestinal failure due to inadequate intestinal length ("short bowel syndrome"/SBS). Treatment in these patients remains challenging and the process of physiologic adaptation may take years to complete, which frequently requires parenteral nutrition. We propose a proof-of-concept mechanical bowel elongation approach using a self-expanding prototype of an intestinal expansion sleeve (IES) for use in SBS to accelerate the adaptation process.

Methods: IESs were deployed in the small intestines of Sprague Dawley rats. Mechanical characterization of these prototypes was performed. IES length-tension relationships and post-implant bowel expansion were measured ex vivo. Bowel histology before and after implantation was evaluated.

Results: IES mechanical studies demonstrated decreasing expansive force with elongation. The deployment of IES devices produced an immediate 21 ± 8% increase in bowel length (p < 0.001, n = 11). Mechanical load testing data showed that the IESs expressed maximum expansive forces at 50% compression of the initial pre-contracted length. The small-intestine failure load in the rats was 1.88 ± 21 N. Intestinal histology post deployment of the IES showed significant expansive changes compared to unstretched bowel tissue.

Conclusions: IES devices were scalable to the rat intestinal model in our study. The failure load of the rat small intestine was many times higher than the force exerted by the contraction of the IES. Histology demonstrated preservation of intestinal structure with some mucosal erosion. Future in vivo rat studies on distraction enterogenesis with this IES should help to define this organogenesis phenomenon.

Background: Autism spectrum disorder (ASD) is one of the most prevalent neurodevelopmental disorders. Many patients with ASD often show behavioral problems at mealtimes, including food selectivity and atypical feeding behaviors. The Mediterranean diet (MD) has a beneficial effect on mental health for the general population across different ages. There is evidence that good adherence to the MD is effective in reducing peripheral inflammatory markers, such as the cytokine interleukin-6 (IL-6). The present study was designed to evaluate adherence to the MD in children with ASD using age- and sex-matched, typically developing individuals (TDs) as a control group and to determine whether differences in adherence to the MD are associated with salivary IL-6 and IL-6 receptor concentration.

Methods: Twenty children and adolescents with ASD (mean age 9.95 ± 0.65 years) and twenty TDs (mean age: 9.85 ± 0.59 years) participated in this study (N = 16 males and N = 4 females in each group). Participants with ASD were enrolled in a psychiatric consultation in Valencia (Spain), and TDs were recruited from two public schools in Valencia. The parents of both ASD and TD groups answered the items in a validated Mediterranean Diet Quality Index for children and adolescents (KIDMED) questionnaire on their children's adherence to the MD.

Results: The mean adherence to MD score was significantly lower in the ASD group (9.10 ± 0.42) (range 6-12) than in the TD group (10.35 ± 0.31) (range 8-12) (p = 0.02, Mann-Whitney U test). There was no statistically significant association between adherence to the MD and age or sex in both groups, but there was a significant correlation between the total KIDMED score and body mass index (BMI) in the ASD group. Regarding the concentration of Il-6 and the Il-6 receptor in saliva samples, there were no significant differences between the two groups; however, linear regression analysis by group revealed significant associations between the adherence to MD score and the concentration of IL-6 and its receptor in saliva in the ASD group (p = 0.003, OR = 0.68, 95% CI 0.007 to -0.02; p = 0.009, OR = -0.64, 95% CI -0.01 to -0.00). In contrast, no significant associations were observed between the adherence to MD score and the concentration of IL-6 and its receptor in saliva in the TD group.

Conclusions: Children and adolescents with ASD showed significantly lower adherence to the MD, which can contribute to nutritional deficits described in ASD, and the role of BMI composition (fat versus lean mass) needs to be further investigated in this group. The concentration of IL-6 and its receptor in saliva is associated with adherence to the MD, suggesting a possible link between IL-6 and diet in ASD. Further studies to clarify the associations between IL-6, psychiatric alterations, and diet in ASD are needed.

Background: Atrial fibrillation (AF) significantly contributes to acute ischemic stroke, with undetected AF being a common culprit in cryptogenic strokes. N-terminal pro-B-type natriuretic peptide (NT-proBNP), indicative of myocardial stress, has been proposed as a biomarker for AF detection, aiding in the selection of patients for extended cardiac monitoring. However, the diagnostic accuracy of NT-proBNP remains uncertain.

Methods: We conducted a meta-analysis to evaluate the diagnostic accuracy of NT-proBNP in detecting AF among cryptogenic stroke patients. A comprehensive literature search was conducted across PubMed, Embase, and Cochrane databases to identify relevant studies. Studies reporting NT-proBNP levels in stroke patients and data on the proportion of patients with AF above a specified cut-off were included. Meta-analyses were performed using the midas command in STATA.

Results: Seven studies encompassing 2171 patients were included in the analysis, of which five studies contained cohorts with cryptogenic strokes. Among patients with cryptogenic stroke, NT-proBNP demonstrated a diagnostic accuracy of 80% (Area Under the Receiver Operating Curve 0.80 [95% CI 0.76-0.83]), with a sensitivity of 81% (95% CI 0.68-0.89) and a specificity of 68% (95% CI 0.60-0.75).

Conclusion: Our meta-analysis indicates that NT-proBNP exhibits a good-to-very-good diagnostic accuracy for detecting AF in patients with cryptogenic stroke. These findings suggest potential implications for utilizing NT-proBNP in guiding the selection of patients for prolonged cardiac monitoring, thereby aiding in the management of cryptogenic stroke cases.

Understanding how gut flora interacts with oxidative stress has been the subject of significant research in recent years. There is much evidence demonstrating the existence of the microbiome-oxidative stress interaction. However, the biochemical basis of this interaction is still unclear. In this narrative review, possible pathways of the gut microbiota and oxidative stress interaction are presented, among which genetic underpinnings play an important role. Trimethylamine-N-oxide, mitochondria, short-chain fatty acids, and melatonin also appear to play roles. Moreover, the relationship between oxidative stress and the gut microbiome in obesity, metabolic syndrome, chronic ethanol consumption, dietary supplements, and medications is considered. An investigation of the correlation between bacterial community features and OS parameter changes under normal and pathological conditions might provide information for the determination of new research methods. Furthermore, such research could contribute to establishing a foundation for determining the linkers in the microbiome-OS association.

Bronchial asthma (BA) continues to be a difficult disease to diagnose. Various factors have been described in the development of BA, but to date, there is no clear evidence for the etiology of this chronic disease. The emergence of COVID-19 has contributed to the pandemic course of asthma and immunologic features. However, there are no unambiguous data on asthma on the background and after COVID-19. There is correlation between various trigger factors that provoke the development of bronchial asthma. It is now obvious that the SARS-CoV-2 virus is one of the provoking factors. COVID-19 has affected the course of asthma. Currently, there is no clear understanding of whether asthma progresses during or after COVID-19 infection. According to the results of some studies, a significant difference was identified between the development of asthma in people after COVID-19. Mild asthma and moderate asthma do not increase the severity of COVID-19 infection. Nevertheless, oral steroid treatment and hospitalization for severe BA were associated with higher COVID-19 severity. The influence of SARS-CoV-2 infection is one of the protective factors. It causes the development of severe bronchial asthma. The accumulated experience with omalizumab in patients with severe asthma during COVID-19, who received omalizumab during the pandemic, has strongly suggested that continued treatment with omalizumab is safe and may help prevent the severe course of COVID-19. Targeted therapy for asthma with the use of omalizumab may also help to reduce severe asthma associated with COVID-19. However, further studies are needed to prove the effect of omalizumab. Data analysis should persist, based on the results of the course of asthma after COVID-19 with varying degrees of severity.

The present study investigated the influence of SCUBA dives with compressed air at depths of 10 and 20 m on ECG-derived HRV parameters in apparently healthy individuals. We hypothesized that cardiac sympathetic activity (measured by HRV parameters) adapts proportionally to diving depth, and that both time- and frequency-domain parameters are sensitive enough to track changes in cardiac ANS function during diving activities and subsequently during the recovery period. Eleven healthy middle-aged recreational divers (nine men and two women, age 43 ± 8, all nonsmokers) volunteered to participate in the present study. The participants (all open-circuit divers) were equipped with dry suits and ECG Holter devices and were later randomly assigned to dive pairs and depths (10 m vs. 20 m), and each participant served as his or her own control. No interaction effects (diving depth x time epoch) were found for the most commonly used HRV markers. More precisely, in response to two different diving protocols, a significant post hoc effect of time was observed for HR and SDNN, as these parameters transiently decreased during the dives and returned to baseline after ascent (p < 0.001). The ULF, VLF (p < 0.003), TP, and LF parameters decreased significantly during the dives, while HF significantly increased (p < 0.003). SCUBA diving apparently challenges the cardiac ANS, even in healthy individuals. The observed changes reveal possible underwater methods of influencing the parasympathetic activity of the heart depending on the depth of the dive. These results identify autonomic nervous system markers to track the cardiovascular risk related to diving and point to the possibility of tracking cardiovascular system benefits during underwater activities in selected patients.

Atherosclerosis is caused by cholesterol accumulation within arteries. The intima is where atherosclerotic plaque accumulates and where lipid-laden foam cells reside. Intimal foam cells comprise of both monocyte-derived macrophages and macrophage-like cells (MLC) of vascular smooth muscle cell (VSMC) origin. Foam cells can remove cholesterol via apoAI-mediated cholesterol efflux and this process is regulated by the transporter ABCA1. The microRNA miR-33a-5p is thought to be atherogenic via silencing ABCA1 which promotes cholesterol retention and data has shown inhibiting miR-33a-5p in macrophages may be atheroprotective via enhancing apoAI-mediated cholesterol efflux. However, it is not entirely elucidated whether precisely inhibiting miR-33a-5p in MLC also increases ABCA1-dependent cholesterol efflux. Therefore, the purpose of this work is to test the hypothesis that inhibition of miR-33a-5p in cultured MLC enhances apoAI-mediated cholesterol efflux. In our study, we utilized the VSMC line MOVAS cells in our experiments, and cholesterol-loaded MOVAS cells to convert this cell line into MLC. Inhibition of miR-33a-5p was accomplished by transducing cells with a lentivirus that expresses an antagomiR directed at miR-33a-5p. Expression of miR-33a-5p was analyzed by qRT-PCR, ABCA1 protein expression was assessed via immunoblotting, and apoAI-mediated cholesterol efflux was measured using cholesterol efflux assays. In our results, we demonstrated that lentiviral vector-mediated knockdown of miR-33a-5p resulted in decreasing expression of this microRNA in cultured MLC. Moreover, reduction of miR-33a-5p in cultured MLC resulted in de-repression of ABCA1 expression, which caused ABCA1 protein upregulation in cultured MLC. Additionally, this increase in ABCA1 protein expression resulted in enhancing ABCA1-dependent cholesterol efflux through increasing apoAI-mediated cholesterol efflux in cultured MLC. From these findings, we conclude that inhibiting miR-33a-5p in MLC may protect against atherosclerosis by promoting ABCA1-dependent cholesterol efflux.