Microbiome-metabolomics-based insight into the protective effects of dietary fiber from sweetpotato residues on the high-fat diet-induced intestinal integrity damage.

Dietary fibers have attracted much attention due to their multiple benefits on gut health. In this work, the protective mechanism of dietary fiber from sweetpotato residues (SRDF) on the high-fat diet (HFD)-induced intestinal barrier injury was investigated using microbiome-metabolomics-based approach. The physicochemical property analysis demonstrated a thermal stability below 200 °C and porous pectin-polysaccharide structure of SRDF with high in vitro functional activities. The biochemical analysis indicated that SRDF significantly ameliorated intestinal barrier function by improving intestinal morphology and permeability and inhibiting inflammatory response. Microbiome analysis demonstrated that SRDF significantly reversed the HFD-induced dysbacteriosis, decreased the ratio of Firmicutes/Bacteroides and enhanced the relative abundance of probiotics, such as Muribaculaceae and Bifidobacteriaceae. Metabolomics analysis showed that SRDF also significantly altered the metabolic profile in the colon, wherein the differential metabolites were mainly involved in amino acid metabolism (especially tryptophan). Pearson correlation coefficient identified the beneficial relationship between intestinal microbiome and metabolome induced by SRDF. The limitation of this study was that the mouse model may not fully replicate the human intestinal responses due to the difference between the standard environmental conditions and natural world. Generally, our results implied the great potential of SRDF as a functional food ingredient.

The relationship between ischemic penumbra progression and the oxygen content of cortex microcirculation in acute ischemic stroke.

The precise oxygen content thresholds of ischemic deep parenchymal (OCIDP) and that in cortical microcirculation (OCCM), which leads to ischemic penumbra converting into the infarcted core, remain uncertain. This study employed an invasive fiber-optic oxygen meter and a newly developed oxygen-responsive probe called RuA3-Cy5-rtPA (RC-rtPA) based on recombinant tissue-type plasminogen activator (rtPA) to examine the oxygen content thresholds. A mouse model of middle cerebral artery occlusion was generated and animals were randomly divided into a sham, 24-h reperfusion after 3-h ischemia (IR 3-h), and IR 6-h groups, all of which were sacrificed following reperfusion. Stroke severity was evaluated based on the infarction area, neurological symptoms, microcirculation perfusion, and microemboli in microcirculation. OCIDP was characterized based on its extent and distribution, whereas OCCM was measured using RC-rtPA. During ischemia, stroke severity escalation manifested as increasing infarction area, severe neurologic symptoms, and poorer microcirculation perfusion with more microthrombi depositions. OCIDP presented rapid decline following artery occlusion along with a gradual increase in the hypoxic area. Within 3 â€‹h following ischemia induction, the ischemic tissue that experienced hypoxia could be rescued, and this reversibility would disappear after 6 â€‹h. Within 6 â€‹h, OCCM continued to decrease. A significant decrease in oxygen content in cortical venules and cortical parenchyma was observed. These findings assist in establishing the extent of the ischemic penumbra at the microcirculation level and offer a foundation for assessing the ischemic penumbra that could respond positively to reperfusion therapy beyond the typical time window.

Long-Term Efficacy and Safety of Low-Dose Rituximab in Patients with Refractory Myasthenia Gravis.

INTRODUCTION: Rituximab is a monoclonal chimeric antibody against CD20+ B cells. We aimed to assess the long-term efficacy and safety of CD20+ B cell-guided treatment with low-dose rituximab in refractory myasthenia gravis patients. METHODS: Patients with refractory myasthenia gravis treated with rituximab for more than 2 years were included. Rituximab was administered when CD20+ B cells were greater than 1%. We analysed the efficacy of rituximab, treatment interval, side effects, prognosis, and treatment course. RESULTS: A total of 22 patients were included. All patients received 2-12 doses of rituximab, and the median follow-up time was 48.5 months. The scores of the Myasthenia Gravis Activities of Daily Living and Myasthenia Gravis Composite were significantly lower than those at baseline (p < 0.05). MGFA-PIS was significantly improved in 21 (95.45%) patients and 14 (63.64%) patients have reached MGFA-PIS minimal manifestations. The average daily dose of prednisone and pyridostigmine bromide and the proportion of immunosuppressants were significantly lower (p < 0.05). Seven patients suffered from 14 worsenings. Eight patients terminated rituximab due to good efficacy. Most patients tolerated rituximab well, although 1 patient had opportunistic infection and hypogammaglobulinemia, 1 patient had an intracranial mass. CONCLUSION: Long-term CD20+ B-cell-guided low-dose rituximab showed good efficacy and tolerance in patients with refractory myasthenia gravis.

Efficacy and safety of long-term immunotherapy in adult patients with MOG antibody disease: a systematic analysis.

OBJECTIVE: To summarise the evidence of the efficacy and safety of current long-term immunotherapies in patients with myelin oligodendrocyte glycoprotein antibody disease (MOG-AD). METHODS: We performed a sensitive literature search in MEDLINE and EMBASE for selected studies or case series discussing the long-term treatments and outcomes in adult patients with MOG-AD and conducted a qualitative analysis of each therapy. RESULTS: A total of 33 articles, including 712 patients with MOG-AD, matched our inclusion criteria, and seven kinds of drugs were analysed accordingly. Efficacy was mainly reflected by the change in the annual relapse rate before and after treatment. First, maintenance steroids, azathioprine, mycophenolate mofetil, and rituximab were demonstrated to be effective in multiple studies. However, relapses could still happen after therapy especially under specific circumstances. Second, regular intravenous immunoglobulin G (IVIG) and tocilizumab might be effective. IVIG reduced annual relapse rate and expanded disability status scale in five adult patients, and tocilizumab succeeded in preventing relapse in four refractory patients, though with scant evidence. Finally, multiple sclerosis-disease-modifying therapy seemed ineffective for patients with MOG-AD. As for safety, six patients experienced severe neutropenia during rituximab therapy. No other serious adverse events were reported for these treatments. CONCLUSIONS: Several preventive immunotherapies have been demonstrated to be effective and safe for adult patients with MOG-AD; however, large controlled studies for subgroups with specific manifestations are still needed in the future.

A long-term follow-up of rituximab treatment in 20 Chinese patients with neuromyelitis optica spectrum disorders.

BACKGROUND: Rituximab has been recommended as the first-line therapy for neuromyelitis optica spectrum disorders (NMOSD); however, its regimen is yet to be optimised. We aimed to present our experience of treating adult Chinese patients having NMOSD with low-dose rituximab, and to further investigate its efficacy and safety in a long-term follow-up. METHODS: Twenty adult Chinese patients with NMOSD, who had received rituximab injections, were retrospectively analysed, and followed up over a long time in our hospital. Efficacy was evaluated mainly by the change in expanded disability status scale and annual relapse ratio before and after rituximab therapy. Safety was reflected by the incidence and severity of side effects. RESULTS: Rituximab regimens, including doses and intervals, varied widely across patients. The median dose was 500 mg, ranging from 100 mg to 1000 mg. The median interval was 6.1 months, ranging from 2 months to 18 months. After rituximab therapy, the median EDSS was stable, whereas median ARR decreased by 90%. Of the 20 patients, 9 suffered from 11 relapses, with relapse-free rate of 55%. Six relapsing cases occurred in less than 6 months from the preceding rituximab injection. Seven cases occurred without CD19+ B cell repopulation. There were 4 cases of infection, including lung and urinary infection; severity ranged from mild to severe across the patients. CONCLUSIONS: We confirmed the long-term efficacy and safety of low-dose rituximab in adult Chinese patients with NMOSD. We recommend monitoring of B cell repopulation to instruct individualised regimens for patients with NMOSD in clinical practice.

Gene ontology analysis of the TNF signaling pathway in early orthodontic tooth movement of rats with periodontitis / 口腔疾病防治

Objective@#To investigate the expression and function of the TNF signaling pathway in the early stage of orthodontic tooth movement with periodontitis and to provide evidence to study the early inflammatory response in patients with periodontitis orthodontic treatment. @*Methods@#Sixteen SD rats were randomly divided into four groups: group A--12 h of orthodontic tooth movement of the bilateral maxillary first molars in rats with periodontitis; group B--periodontitis model of the bilateral maxillary first molars without orthodontic tooth movement; group C--12 h of orthodontic tooth movement of the same teeth in rats with healthy periodontium; group D--control group without operations. The bilateral maxillary first molars and surrounding periodontal tissue of each group were collected for gene chip detection. Pathway enrichment analysis, qRT-PCR and GO (gene ontology) analysis were performed to identify differential genes involved in the TNF signaling pathway. @*Results @#Gene chip results showed that the TNF signaling pathway was significantly upregulated in group A, group B and group C (P <0.01). Among the differential genes involved in the pathway, 28 were upregulated and 5 were downregulated in group A, 12 were upregulated and 4 were downregulated in group B, and 12 were upregulated and 1 was downregulated in group C (P <0.05). The most significant GO items included "response to lipopolysaccharide", "inflammatory response", "positive regulation of NF-κB transcription factor activity", "positive regulation of NF-κB import into nucleus" and "response to hypoxia"(P <0.001). qRT-PCR results showed no significant difference in TNF-α mRNA expression in group C compared with that in group D, TNF-α was upregulated in both groups A and B (P <0.01), and mRNA expression decreased in the following order: group A > group B > group C (P <0.05). Compared with group D, the expression levels of prostaglandin-endoperoxide synthase 2 (PTGS2) and interleukin-6 ( IL-6) in groups A, B and C were significantly upregulated (P <0.05), but the expression levels of PTGS2 and IL-6 in group A were lower than those in group B (P < 0.05). @*Conclusion@#The TNF signaling pathway is activated in the early stage of orthodontic tooth movement in rats with periodontitis. The pathway products participate in many biological processes and play an important role in the inflammatory response and bone absorption.