BackgroundAntibiotic-associated diarrhea (AAD) is a risk factor for exacerbating the outcome of critically ill patients. Dysbiosis induced by the exposure to antibiotics reveals the potential therapeutic role of fecal microbiota transplantation (FMT) in these patients. Herein, we aimed to evaluate the safety and potential benefit of rescue FMT for AAD in critically ill patients.MethodsA series of critically ill patients with AAD received rescue FMT from Chinese fmtBank, from September 2015 to February 2019. Adverse events (AEs) and rescue FMT success which focused on the improvement of abdominal symptoms and post-ICU survival rate during a minimum of 12 weeks follow-up were assessed.ResultsTwenty critically ill patients with AAD underwent rescue FMT, and 18 of them were included for analysis. The mean of Acute Physiology and Chronic Health Evaluation (APACHE) II scores at intensive care unit (ICU) admission was 21.7 ± 8.3 (range 11–37). Thirteen patients received FMT through nasojejunal tube, four through gastroscopy, and one through enema. Patients were treated with four (4.2 ± 2.1, range 2–9) types of antibiotics before and during the onset of AAD. 38.9% (7/18) of patients had FMT-related AEs during follow-up, including increased diarrhea frequency, abdominal pain, increased serum amylase, and fever. Eight deaths unrelated to FMT occurred during follow-up. One hundred percent (2/2) of abdominal pain, 86.7% (13/15) of diarrhea, 69.2% (9/13) of abdominal distention, and 50% (1/2) of hematochezia were improved after FMT. 44.4% (8/18) of patients recovered from abdominal symptoms without recurrence and survived for a minimum of 12 weeks after being discharged from ICU.ConclusionIn this case series studying the use of FMT in critically ill patients with AAD, good clinical outcomes without infectious complications were observed. These findings could potentially encourage researchers to set up new clinical trials that will provide more insight into the potential benefit and safety of the procedure in the ICU.Trial registrationClinicalTrials.gov, Number NCT03895593. Registered 29 March 2019 (retrospectively registered).
Cystatin C, a well-established biomarker of renal function, has been associated with a protective effect against stroke. However, the potential neuroprotective mechanism of cystatin C in ischemic brain injury remains unclear. Our study hypothesized that cystatin C can ameliorate blood-brain barrier (BBB) disruption by up-regulating caveolin-1 expression, thereby improving neurological outcomes in cerebral ischemic injury. Western blotting, immunohistochemistry, immunofluorescence staining, and immunoprecipitation were performed to investigate target proteins. Evans Blue and gelatin zymography were used to examine the effect of cystatin C on BBB disruption. Plasmid and small interfering RNA transfection was used to observe alterations in caveolin-1 and occludin expression induced by changes in cystatin C expression. Intriguingly, our study showed that the expression of both cystatin C and caveolin-1 was increased in middle cerebral artery occlusion-injured mice, and pretreatment with exogenous cystatin C significantly increased caveolin-1 expression, reduced Evans Blue leakage in the injured brain region, and decreased the enzymatic activity of matrix metallopeptidase-9. Meanwhile, our study also showed that the over-expression of cystatin C greatly enhanced caveolin-1 expression, which later increased occludin expression in oxygen-glucose deprivation-exposed brain microvascular endothelial cells. The knockdown of cystatin C induced the opposite outcomes. These experimental results indicate a positive role for cystatin C in the regulation of caveolin-1 and occludin expression in cerebral ischemic injury. Taken together, these data unveil a new mechanism of the regulation of caveolin-1 expression by cystatin C in the maintenance of BBB integrity after ischemic brain injury and provide new clues for the identification of potential therapeutic strategies for stroke. Keywords: bEnd.3, blood-brain barrier, caveolin-1, cystatin C, ischemic brain injury, occludin. are co-first authors.Abbreviations used: BBB, blood-brain barrier; bEnd.3, brain microvascular endothelial; DMEM, Dulbecco's modified Eagle medium; I/R, ischemia/reperfusion; ICV, intracerebroventricular; MCAO, middle cerebral artery occlusion; MMP-9, matrix metallopeptidase-9; MMPs, matrix metalloproteinases; OGD, oxygen-glucose deprivation; PBS, phosphate buffered saline; SDS, sodium dodecyl sulfate; siRNA, small interfering RNA. | 2020 | 153 | 413-425 JOURNAL OF NEUROCHEMISTRY
Postoperative cognitive decline is a major clinical problem with high morbidity and mortality after surgery. Many studies have found that molecular hydrogen (H2) has significant neuroprotection against acute and chronic neurological injury by regulating inflammation and apoptosis. In this study, we hypothesized that H2 treatment could ameliorate the development of cognitive impairment following surgery. Adult male rats were subjected to stabilized tibial fracture operation under anesthesia. Two percent of H2 was inhaled for 3 h beginning at 1 h after surgery. Separate cohorts of rats were tested for cognitive function with fear conditioning and the Y-maze test, or euthanized to assess blood-brain barrier integrity, and systemic and hippocampal proinflammatory cytokine and caspase-3 activity. Surgery-challenged animals showed significant cognitive impairment evidenced by a decreased percentage of freezing time and an increased number of learning trials on days 1, 3, and 7 after operation, which were significantly improved by H2 treatment. Furthermore, H2 treatment significantly ameliorated the increase in serum and hippocampal proinflammatory cytokines tumor necrosis factor-α, interleukin-1β, interleukin-6, and high-mobility group protein 1 in surgery-challenged animals. Moreover, H2 treatment markedly improved blood-brain barrier integrity and reduced caspase-3 activity in the hippocampus of surgery-challenged animals. These findings suggest that H2 treatment could significantly mitigate surgery-induced cognitive impairment by regulating inflammation and apoptosis.
This study aimed to investigate the role of microRNA-181b-5p (miR-181b-5p) in starvation-induced cardiomyocyte autophagy by targeting heat shock protein family A member 5 (Hspa5). For this purpose, H9c2 cardiomyocytes and neonatal rat ventricular myocytes (NRVMs) were glucose-starved in Earle's Balanced Salt Solution (EBSS) for different periods of time (0, 2, 4, 6 and 8 h). RT-qPCR analysis was performed to examine the expression of miR-181b-5p in the different groups. Immunofluorescence was performed to detect the expression of LC3. In addition, the H9c2 cardiomyo-cytes and NRVMs were transfected with miR-181b-5p mimic, miR-181b-5p inhibitor, siHspa5 or their respective controls. An MTT assay was performed to measure cell proliferation in the different groups. Western blot analysis was performed to determine the expression of Beclin-1, Hspa5, phosphorylated phosphoinositide 3-kinase PI3K (p-PI3K), phosphorylated Akt (p-Akt), phosphorylated mammalian target of rapamycin (p-mTOR), Bcl-2, Bax and cleaved caspase-3. Flow cytometry was performed to assess cell apoptosis. A luciferase reporter assay was performed to determine whether Hspa5 is a direct target of miR-181b-5p. The results revealed that the down-regulation of miR-181b-5p promoted cell autophagy in the cardiomyocytes. Moreover, miR-181b-5p negatively regulated Beclin-1 and Hspa5. Beclin-1 is a well-known autophagy- and apoptosis-related protein. In addition, cell apoptosis was attenuated by the decreased expression of miR-181b-5p in the cardiomyocytes. Bcl-2 prevented apoptosis and autophagy by binding to Bax and Bcl-2, respectively. The upregulation of miR-181b-5p inhibited autophagy and promoted apoptosis via Hspa5. miR-181b-5p inhibition promoted p-mTOR, p-Akt and p-PI3K expression via Hspa5. The results of luciferase reporter assay also confirmed that Hspa5 is a direct target of miR-181b-5p. On the whole, the findings of this study suggest that miR-181b-5p contributes to starvation-induced autophagy and apoptosis in cardiomyocytes by directly targeting Hspa5 via the PI3K/Akt/mTOR signaling pathway.
Intravenous ketamine infusion significantly reduced postoperative pain scores and opioid consumption after LC. In addition, there were fewer adverse effects in the ketamine groups. Higher quality RCTs are still required for further research.
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