Crohn's disease as the intestinal manifestation of pan-lymphatic dysfunction: An exploratory proposal based on basic and clinical data.

Crohn's disease (CD) is caused by immune, environmental, and genetic factors. It can involve the entire gastrointestinal tract, and although its prevalence is rapidly increasing its etiology remains unclear. Emerging biological and small-molecule drugs have advanced the treatment of CD; however, a considerable proportion of patients are non-responsive to all known drugs. To achieve a breakthrough in this field, innovations that could guide the further development of effective therapies are of utmost urgency. In this review, we first propose the innovative concept of pan-lymphatic dysfunction for the general distribution of lymphatic dysfunction in various diseases, and suggest that CD is the intestinal manifestation of pan-lymphatic dysfunction based on basic and clinical preliminary data. The supporting evidence is fully summarized, including the existence of lymphatic system dysfunction, recognition of the inside-out model, disorders of immune cells, changes in cell plasticity, partial overlap of the underlying mechanisms, and common gut-derived fatty and bile acid metabolism. Another benefit of this novel concept is that it proposes adopting the zebrafish model for studying intestinal diseases, especially CD, as this model is good at presenting and mimicking lymphatic dysfunction. More importantly, the ensuing focus on improving lymphatic function may lead to novel and promising therapeutic strategies for CD.

Continuous renal replacement therapy with oXiris® in patients with hematologically malignant septic shock: A retrospective study.

BACKGROUND: The mortality rate from septic shock in patients with hematological malignancies (HMs) remains significantly higher than that in patients without HMs. A longer resuscitation time would definitely be harmful because of the irreversibly immunocompromised status of the patients. Shortening the resuscitation time through continuous renal replacement therapy (CRRT) with oXiris® would be an attractive strategy in managing such patients. AIM: To explore the effects of CRRT and oXiris® in shortening the resuscitation time and modifying the host response by reducing inflammation mediator levels. METHODS: Forty-five patients with HM were diagnosed with septic shock and underwent CRRT between 2018 and 2022. Patients were divided into two groups based on the hemofilter used for CRRT (oXiris® group, n = 26; M150 group, n = 19). We compared the number of days of negative and total fluid balance after 7 d of CRRT between the groups. The heart rate, norepinephrine dose, Sequential Organ Failure Assessment (SOFA) score, and blood lactic acid levels at different time points in the two groups were also compared. Blood levels of inflammatory mediators in the 26 patients in the oXiris® group were measured to further infer the possible mechanism. RESULTS: The average total fluid balance after 7 d of CRRT in the oXiris® group was significantly lower than that of patients in the M150 hemofilter group. The SOFA scores of patients after CRRT with oXiris® therapy were significantly lower than those before treatment on day 1 (d1), d3 and d7 after CRRT; these parameters were also significantly lower than those of the control group on d7. The lac level after oXiris® therapy was significantly lower than that before treatment on d3 and d7 after CRRT. There were no significant differences in the above parameters between the two groups at the other time points. In the oXiris® group, procalcitonin levels decreased on d7, whereas interleukin-6 and tumor necrosis factor levels decreased significantly on d3 and d7 after treatment. CONCLUSION: CRRT with oXiris® hemofilter may improve hemodynamics by reducing inflammatory mediators and playing a role in shortening the resuscitation period and decreasing total fluid balance in the resuscitation phases.

Antagonizing adipose tissue-derived exosome miR-103-hepatocyte phosphatase and tensin homolog pathway alleviates autophagy in non-alcoholic steatohepatitis: A trans-cellular crosstalk.

BACKGROUND: Obesity plays a vital role in the occurrence and development of non-alcoholic steatohepatitis (NASH). However, the underlining mechanism is still unclear, where adipose tissue (AT) derived exosomes may actively participate. MicroRNAs (miRNAs) are commonly secreted from exosomes for cell communication. Though the regulation of miR-103 on insulin sensitivity has been reported, the specific role of AT-derived exosomes miR-103 in NASH is still vague and further investigation may provide novel therapeutic choices. AIM: To determine the specific role of AT-derived exosomes miR-103 in developing NASH through various methods. METHODS: The expression levels of miR-103 in the AT-derived exosomes and livers were detected and compared between NASH mice and control. The effect of miR-103 on NASH progression was also explored by antagonizing miR-103, including steatosis and inflammation degree changes. The interaction between miR-103 and the autophagy-related gene phosphatase and tensin homolog (PTEN) was confirmed by dual-luciferase reporter assay. The role of the interaction between miR-103 and PTEN on autophagy was verified in NASH-like cells. Finally, the effects of miR-103 from adipose-derived exosomes on NASH and autophagy were analyzed through animal experiments. RESULTS: The expression of miR-103 was increased in NASH mice, compared to the control, and inhibition of miR-103 could alleviate NASH. The results of the dual-luciferase reporter assay showed miR-103 could interact with PTEN. MiR-103-anta decreased p-AMPKa, p-mammalian target of rapamycin (mTOR), and p62 but increased the protein levels of PTEN and LC3-II/I and the number of autophagosomes in NASH mice. Similar results were also observed in NASH-like cells, and further experiments showed PTEN silencing inhibited the effect of miR-103-anta. AT derived-exosome miR-103 aggravated NASH and increased the expressions of p-AMPKa, p-mTOR, and p62 but decreased the protein levels of PTEN and LC3-II/I and the number of autophagosomes in mice. CONCLUSION: AT derived-exosome increased the levels of miR-103 in the liver, and miR-103 aggravated NASH. Mechanically, miR-103 could interact with PTEN and inhibit autophagy.

Performance and mechanism of different pretreatment methods for inoculated sludge in biohydrogen production.

A comparison was conducted between pre-culture bacteria (PCB) and heat treatment anaerobic granular sludge (HTAGS) for hydrogen production, and it was found that hydrogen molar yield (HMY) of PCB was 21-35% higher than that of HTAGS. The addition of biochar increased hydrogen production in both cultivation methods by acting as an electron shuttle to enhance extracellular electron transfers of Clostridium and Enterobacter. On the other hand, Fe3O4 did not promote hydrogen production in PCB experiments but had a positive effect on HTAGS experiments. This was due to the fact that PCB was mainly composed of Clostridium butyricum, which could not reduce extracellular iron oxide, resulting in a lack of respiratory driving force. In contrast, HTAGS retained a significant amount of Enterobacter, which possess the ability of extracellular anaerobic respiration. Different pretreatment methods of inoculum resulted in significant changes in the sludge community, thus exerting a noticeable impact on biohydrogen production.

High-fat diet aggravates colitis via mesenteric adipose tissue derived exosome metastasis-associated lung adenocarcinoma transcript 1.

BACKGROUND: Obesity is associated with an increased risk of developing Crohn's disease (CD), higher disease activity, and comparatively worse clinical outcomes. AIM: To investigate the role of mesenteric adipose tissue-derived exosomes in the pathogenesis of CD aggravation in obese individuals. METHODS: First, we induced colitis in mice initiated on high-fat and normal diets and compared the severity of colitis. We then extracted and identified exosomes from mesenteric adipose tissue and determined the levels of metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) in mesenteric adipose tissue-derived exosomes and the colon. Next, we demonstrated an interaction between MALAT1 and the miR-15a-5p/activating transcription factor 6 (ATF6) axis. Finally, we explored the effects of mesenteric adipose tissue-derived exosomes extracted from mice fed a high-fat or normal diet on the severity of 2,4,6-trinitrobe-nzenesulfonic acid (TNBS)-induced colitis and ATF6-related endoplasmic reticulum stress pathways. RESULTS: High-fat diet was found to aggravate TNBS-induced colitis in mice. The expression of MALAT1 in mesenteric adipose tissue-derived exosomes of high-fat diet-fed mice increased. The increased expression of MALAT1 in colon tissue exacerbated TNBS-induced colitis and activated the ATF6 endoplasmic reticulum stress pathway. This effect was partially reversed by the reduced expression of MALAT1 and overexpression of miR-15a-5p. CONCLUSION: Mesenteric adipose tissue-derived exosome-encapsulated long noncoding RNAs MALAT1 targets the colon and aggravates TNBS-induced colitis in obese mice, which may potentially act on the miR-15a-5p/ATF6 axis and activate endoplasmic reticulum stress.

The enhancement on biohydrogen production by the driving forces from extracellular iron oxide respiration.

Biohydrogen productions from xylose and glucose under dark condition were enhanced by the presence of natural Fe3O4. The electron equivalent of H2 fractions accounted for 4.55 % and 5.69 % of the total given xylose and glucose in the experiments without Fe3O4, and that were correspondingly increased to 5.14 % and 6.50 % in the experiments with 100 mg/L of Fe3O4, respectively. Moreover, Fe3O4 increased the total intracellular NAD(H) concentrations by 8.84 % and 8.37 %, and boosted the ratios of NADH/NAD+ by 8.33 % and 17.72 % in xylose and glucose fermentation, respectively, comparing to the corresponding control experiments. The formation of electron couples of Fe(III)/Fe(II) during the iron oxide respiration and more generation of active extracellular polymeric substances components were determined as the important reasons for the improved biohydrogen production performance. Thus, a promotion mechanism of the internal "driving forces" from extracellular iron oxide respiration on the biohydrogen production was proposed.

Palmitoylation in Crohn's disease: Current status and future directions.

S-palmitoylation is one of the most common post-translational modifications in nature; however, its importance has been overlooked for decades. Crohn's disease (CD), a subtype of inflammatory bowel disease (IBD), is an autoimmune disease characterized by chronic inflammation involving the entire gastrointestinal tract. Bowel damage and subsequent disabilities caused by CD are a growing global health issue. Well-acknowledged risk factors for CD include genetic susceptibility, environmental factors, such as a westernized lifestyle, and altered gut microbiota. However, the pathophysiological mechanisms of this disorder are not yet comprehensively understood. With the rapidly increasing global prevalence of CD and the evident role of S-palmitoylation in CD, as recently reported, there is a need to investigate the relationship between CD and S-palmitoylation. In this review, we summarize the concept, detection, and function of S-palmitoylation as well as its potential effects on CD, and provide novel insights into the pathogenesis and treatment of CD.

[Soil organic carbon mineralization and priming effects in the topsoil and subsoil under no-tillage black soil.] / è¡¨å±‚å’Œä¸‹å±‚å è€•é»‘åœŸæœ‰æœºç¢³çŸ¿åŒ–é€ŸçŽ‡åŠæ¿€å‘æ•ˆåº”.

Priming effect is one of the important mechanisms regulating soil organic matter decomposition. However, the variation of priming effects in different soil layers remains unclear. In this study, we conducted a 30-day incubation experiment using no-tillage black soil from northeastern China. 13C-glucose and dynamic CO2 trapping methods were employed to investigate soil organic carbon (SOC) mineralization rates and the priming effect of the added 13C-glucose in the upper soil layer (0-10 cm) and the lower soil layer (30-40 cm). Our results showed that the cumulative SOC-specific mineralization rate in the upper layer was similar to that in the lower layer soil without glucose addition. Glucose addition significantly altered the mineralization rates in both layers, resulting in a positive priming effect (36.7%) in the upper layer but a negative priming effect (-12.4%) in the lower layer. The cumulative priming effect during the 30-day incubation was 3.24 mg C·g-1 SOC for the upper layer soil and -1.24 mg C·g-1 SOC for the lower layer soil. There was still a net SOC increase, even with positive priming effects in the upper layer soil. This was due to considerable amount of added glucose-C remained un-mineralized in the soil which would compensate the carbon loss from priming effects. Overall, our results demonstrated that the magnitude and direction of priming effects might differ between soil layers. Our findings contribute to a better understanding of the effects of conservation tillage practices (no-tillage and straw incorporation) on soil organic matter dynamics in agroecosystems.

Habitat-specific patterns and drivers of bacterial ß-diversity in China's drylands.

The existence of biogeographic patterns among most free-living microbial taxa has been well established, yet little is known about the underlying mechanisms that shape these patterns. Here, we examined soil bacterial ß-diversity across different habitats in the drylands of northern China. We evaluated the relative importance of environmental factors versus geographic distance to a distance-decay relationship, which would be explained by the relative effect of basic ecological processes recognized as drivers of diversity patterns in macrobial theoretical models such as selection and dispersal. Although the similarity of bacterial communities significantly declined with increasing geographic distance, the distance-decay slope and the relative importance of factors driving distance-decay patterns varied across different habitats. A strong distance-decay relationship was observed in the alpine grassland, where the community similarity was influenced only by the environmental factors. In contrast, geographic distance was solely responsible for community similarity in the desert. Even the average compositional similarity among locations in the desert was distinctly lower compared with those in other habitats. We found no evidence that dispersal limitation strongly influenced the ß-diversity of bacterial communities in the desert grassland and typical grassland. Together, our results provide robust evidence of habitat specificity for microbial diversity patterns and their underlying drivers. Our findings suggest that microorganisms also have multiple drivers of diversity patterns and some of which may be parallel to some fundamental processes for explaining biodiversity patterns in macroorganisms.

[Distribution pattern of neutral sugar in forest soils along an altitude gradient in Changbai Mountains, Northeast China].

In July 2010, soil samples were collected from five typical forests (Pinus koraiensis and broadleaved mixed forest, Picea and Abies forest, Larix and Abies forest, Betula ermanii forest, and alpine tundra) along an altitude gradient on the northern slope of Changbai Mountains to investigate the distribution and quantity of neutral sugar in the soils and related affecting factors. The origins of the neutral sugar were differentiated to probe into the biochemical accumulation mechanisms of soil organic matter. There was a significant difference in the neutral sugar content among the forest soils. The relative content of soil neutral sugar' s carbon to soil organic carbon ranged in 80.55-170.63 mg C x g(-1), and tended to be increased with elevated altitude. The multiple regression analysis showed that the mean temperature in growth season was the main factor affecting the relative content of soil neutral sugar, and low temperature was conducive to the accumulation of neutral sugar. The ratio of (galactose + mannose) / (arabinose + xylose) in the five soils was around 1.62-2.28, and had an increasing trend with elevated altitude, illustrating that the contribution of soil microbial neutral sugar to soil organic matter increased with elevated altitude. Soil microbial metabolic quotient declined significantly along elevated altitude, suggesting that in low temperature environment, soil microbial activity decreased but the carbon utilization efficiency enhanced. As a result, a significant portion of decomposed plant residues was transformed into microbial neutral sugar and accumulated stably in soil, and thus, increased the proportion of soil microbial neutral sugar.

[Clinical trial to verify the value of the CD14(+) monocyte human leukocyte antigen DR as a marker in evaluating immunosuppression in patients with severe sepsis].

OBJECTIVE: To verify that CD14(+) monocyte human leukocyte antigen DR (HLA-DR) may serve as a reliable index for immunosupression, and for prediction of prognosis as well as to evaluate the efficacy of Thymopentin (TP-5) to enhance immunologic function in patients with severe sepsis, and to evaluate the validity of compensatory anti-inflammatory response syndrome (CARS). METHODS: Patients in a SICU with symptoms and signs of severe sepsis conforming to the criteria set forth by ACCP/SCCM were enrolled in this clinical trial. CD14(+) monocyte HLA-DR was determined by flow cytometry. To those with HLA-DR<30%, TP-5, 1 mg, q.d. was administered till HLA-DR raised or death occurred. Before the treatment was begun and ended, CD14(+) monocyte HLA-DR(+) and cytokines[tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), IL-10, IL-13] were respectively measured. RESULTS: Totally, 20 patients were enrolled in this study. Among them 15 survived and 5 died. After treatment with TP-5, CD14(+) monocyte HLA-DR was elevated in almost all the patients, including the nonsurvivors. However, only a statistically significant difference between the initial values and the final values was noted in the survivors. The levels of TNF-alpha and IL-6 dropped significantly concomitantly with the elevation of the CD14(+) monocyte HLA-DR in survivors. On the contrary, in the patients who died there was a tendency of an elevation of levels of these cytokines. No significant difference was found between the initial and final levels of both IL-10 and IL-13 with the treatment. CONCLUSION: 1. It was reconfirmed that the CD14(+) monocyte HLA-DR could be a reliable and valuable index to judge immunosupression in septic patients and determine the effectiveness of immunostimulative therapy. 2. It was reconfirmed that the level of CD14(+) monocyte HLA-DR can serve as an index to predict the outcome of septic patients. 3. TP-5, as a new immunostimulative agent used in sepsis, might be effective to revert immunosupression. However, a further clinical trial with a larger number of patients and a better control should be done to finally verify it. 4. It is found that immunosupression do not seem to be related with the balance between pro- and anti-inflammatory cytokines, suggesting that the hypothesis of CARS should be further appraised.