Bisindolylmaleimide alkaloid BMA-155Cl induces autophagy and apoptosis in human hepatocarcinoma HepG-2 cells through the NF-κB p65 pathway.

Bisindolylmaleimides, a series of derivatives of a PKC inhibitor staurosporine, exhibit potential as anti-cancer drugs and have received considerable attention in clinical trials. This study aims to investigate the effects of a bisindolylmaleimide alkaloid 155Cl (BMA-155Cl) with a novel structure on autophagy and apoptosis in human hepatocarcinoma HepG-2 cells in vitro and in vivo. The cell poliferation was assessed with a MTT assay. Autophagy was evaluated by MDC staining and TEM analysis. Apoptosis was investigated using Annexin V-FITC/PI and DAPI staining. The antitumor effects were further evaluated in nude mice bearing HepG-2 xenografts, which received BMA-155Cl (10, 20 mg/kg, ip) for 18 days. Autophagy- and apoptosis-associated proteins and their mRNA levels were examined with Western blotting, immunohistochemistry, and RT-PCR. BMA-155Cl (2.5-20 µmol/L) inhibited the growth of HepG-2 cells with IC50 values of 16.62±1.34, 12.21±0.83, and 8.44±1.82 µmol/L at 24, 48, and 72 h, respectively. Furthermore, BMA-155Cl (5-20 µmol/L) dose-dependently induced autophagy and apoptosis in HepG-2 cells. The formation of autophagic vacuoles was induced by BMA-155Cl (10 µmol/L) at approximately 6 h and peaked at approximately 15 h. Pretreatment with 3-MA potentiated BMA-155Cl-mediated apoptotic cell death. This compound dose-dependently increased the mRNA and protein levels of Beclin-1, NF-κB p65, p53, and Bax, but decreased the expression of IκB and Bcl-2. Pretreatment with BAY 11-7082, a specific inhibitor of NF-κB p65, blocked BMA-155Cl-induced expression of autophagy- and apoptosis-associated proteins. BMA-155Cl administration effectively suppressed the growth of HepG-2 xenografts in vivo, and increased the protein expression levels of LC3B, Beclin-1, NF-κB p65, and Bax in vivo. We conclude that the NF-κB p65 pathway is involved in BMA-155Cl-triggered autophagy, followed by apoptosis in HepG-2 cells in vitro and in vivo. Hence, BMA-155Cl could be a promising pro-apoptotic candidate for developing as a novel anti-cancer drug.

Marine natural products sourced from marine-derived Penicillium fungi.

Marine micro-organisms have been proven to be a major source of marine natural products (MNPs) in recent years, in which filamentous fungi are a vital source of bioactive natural products for their large metagenomes and more complex genetic backgrounds. This review highlights the 390 new MNPs from marine-derived Penicillium fungi during 1991 to 2014. These new MNPs are categorized based on the environment sources of the fungal hosts and their bioactivities are summarized.

DHA protects against experimental colitis in IL-10-deficient mice associated with the modulation of intestinal epithelial barrier function.

A defect in the intestinal barrier is one of the characteristics of Crohn's disease (CD). The tight junction (TJ) changes and death of epithelial cells caused by intestinal inflammation play an important role in the development of CD. DHA, a long-chain PUFA, has been shown to be helpful in treating inflammatory bowel disease in experimental models by inhibiting the NF-κB pathway. The present study aimed at investigating the specific effect of DHA on the intestinal barrier function in IL-10-deficient mice. IL-10-deficient mice (IL-10(-/-)) at 16 weeks of age with established colitis were treated with DHA (i.g. 35.5 mg/kg per d) for 2 weeks. The severity of their colitis, levels of pro-inflammatory cytokines, epithelial gene expression, the distributions of TJ proteins (occludin and zona occludens (ZO)-1), and epithelial apoptosis in the proximal colon were measured at the end of the experiment. DHA treatment attenuated the established colitis and was associated with reduced infiltration of inflammatory cells in the colonic mucosa, lower mean histological scores and decreased levels of pro-inflammatory cytokines (IL-17, TNF-α and interferon-γ). Moreover, enhanced barrier function was observed in the DHA-treated mice that resulted from attenuated colonic permeability, rescued expression and corrected distributions of occludin and ZO-1. The results of the present study indicate that DHA therapy may ameliorate experimental colitis in IL-10(-/-) mice by improving the intestinal epithelial barrier function.

Thromboelastography can Identify Postoperative Active Bleeding and Evaluate Blood Product Requirements in Abdominal Surgery.

BACKGROUND/AIMS: Hemorrhage after abdominal surgery remains a frequent clinical complication, and associated with prolonged length of stay, increased complications and mortality. Indication of blood product requirements accurately and promptly is very important for recovery of patients. Thrombelastography (TEG) as a tool for evaluation of bleeding and effects of blood components and blood products is increasing. We investigated that whether TEG can identify postoperative active bleeding and evaluate blood product requirements in abdominal surgery. METHODOLOGY: Between June to December in 2012, there were 55 patients who had bleeding after operation in SICU of Jinling Hospital. Recorded data included vital signs (MAP, heart rate, respiratory rate, blood oxygen saturation), urine volume per hour, blood routine (Hb, Hct, Plt), the coagulation tests (Fib, PT, aPTT, INR), TEG parameters (R, K, Angle, MA, Cl) and blood product requirements within 24h. Patients were divided into active bleeding group and non-active bleeding group based on the findings of reoperation or digital subtraction angiography (DSA). To compare vital signs, laboratory values, TEG values and blood product requirements in two groups. RESULTS: Vital signs (MAP, heart rate, respiratory rate, blood oxygen saturation), urine volume per hour and the coagulation tests (Fib, PT, INR) showed no significant correlations with subsequent blood product requirements, but aPTT (R = 0.546, P = 0.000) and MA (R = 0.665, P = 0.000) correlated with the blood products use. MA values of patients had more blood loss was significantly lower and had a descending tendency which did not showed in aPTT values. 25 patients had postoperative active bleeding confirmed by reoperation or DSA. They had significantly increased use of blood products, and significantly lower MA, Hb, Hct, and Fib values, whereas aPTT exhibited no significant differences. CONCLUSION: MA can not only identify postoperative active bleeding together with hemoglobin, hematocrit, and fibrinogen, but also evaluate blood product requirements in abdominal surgery.

Restricted intravenous fluid regimen reduces fluid redistribution of patients operated for abdominal malignancy.

BACKGROUND/AIMS: Recent studies indicate that perioperative fluid restriction leads to better preserved clinical data as well as reduced complication rates. This study aimed to determine the probable mechanism of fluid restriction influence on the complication rate of patients undergoing gastrointestinal surgery for malignancy. METHODOLOGY: Patients (n = 174) undergoing restricted fluid regimen (R group) or standard fluid regimen (S group) were included in this prospective, randomized trial over 16 months. Fluid distribution was determined by Bioelectrical Impedance Analyzer (BIA) and the difference between two groups was compared regarding complications and the relationship between complications and fluid distribution changes. RESULTS: The restricted intravenous fluid regimen significantly reduced perioperative intravenous fluid volume. Weight gained in S group and was not significantly changed in R group after surgery, especially in POD2 (media; R vs. S; 61.17 vs. 65.40 kg, p = 0.017). The number of patients with postoperative complications was reduced in R group compared with in S group (34.5% vs. 47.8%, p = 0.076). Systemic complications were significantly reduced in R group (t = -5.895, p = 0.000). Patients with complications had an average of 1.6 complications in R group vs. 2.0 in S group (t = -1.345, p = 0.183). The multivariate analysis suggested that perioperative fluid distribution changes were associated with the development of postoperative complications. CONCLUSIONS: Perioperative fluid restriction could effect on fluid distribution and reduce tissue and cellular edema, and further, could reduce postoperative complication rates.

[A comparative study of induction of remission and cost-effectiveness of enteral nutrition versus infliximab in moderate-to-severe Crohn's disease].

OBJECTIVE: To compare the induction of remission and cost-effectiveness of enteral nutrition (EN) and infliximab (IFX) in moderate-to-severe active Crohn's disease(CD). METHODS: Moderate-to-severe active CD patients were divided into IFX group and EN group. Remission rate, time to remission and treatment cost were compared between the two groups. Clinical remission was defined as Crohn's disease activity index (CDAI) < 150. The quality of life was evaluated by inflammatory bowel disease questionnaire of quality of life (IBDQ). RESULTS: A total of 100 patients were analyzed, including 48 patients in IFX group and 52 patients in EN group. IFX group had higher remission rate [87.5% (42/48) vs 67.3% (35/52) , P = 0.017] and shorter time to remission [(11.00 ± 8.35) days vs (33.94 ± 14.60) days, P < 0.001] than EN group. Treatment costs before remission were similar in two groups (P = 0.351) . The increase of IBDQ scores before and after treatment in IFX group was much higher than that of EN group (42.74 ± 27.50 vs 7.57 ± 22.77, P < 0.001) . Similarly, patients in EN group had greater increase of body mass index (BMI) than that of IFX group [(1.32 ± 0.29)kg/m(2) vs (0.51 ± 0.07) kg/m(2), P < 0.001]. For patients with CDAI < 280, remission rate was not significantly different [85.7% (24/28) vs 81.8% (18/22) , P = 0.718] between the two groups, while treatment cost in EN group was less than that of IFX group [(16.1 ± 5.9)×10(3) RMB vs (22.9 ± 11.9)×10(3) RMB, P = 0.021]. CONCLUSIONS: For patients with severe CD (CDAI ≥ 280), IFX has higher remission rate, shorter time to remission and comparable treatment cost than EN. But for patients with CDAI < 280, EN group has comparable remission rate to IFX group with lower cost.

[Surgical treatment for idiopathic abdominal cocoon].

OBJECTIVE: To investigate diagnosis and treatment of abdominal cocoon. METHODS: Clinical data of patients received treatment for abdominal cocoon from January 2000 to January 2011 was retrospectively analyzed. RESULTS: A total of 67 patients underwent treatment in our hospital were analyzed, the preoperatively diagnosis rate was only 47.8% (32/67). Patients who received preoperatively nutrition support have a lower postoperative complication (8/27 vs.13/20, χ(2) = 5.815, P < 0.05) and patients with less extent of intestine involved had a lower early postoperative inflammatory ileus (EPII) rate (9/25 vs. 1/22, χ(2) = 6.912, P < 0.05) when compared with large extent. CONCLUSIONS: Appropriate perioperative management play an important role in the prognosis of abdominal cocoon. The main treatment is surgery while preoperatively nutrition support can reduce postoperative complications.

Postoperative diarrhea in Crohn's disease: Pathogenesis, diagnosis, and therapy.

Diarrhea is a frequent symptom in postoperative patients with Crohn's diseases (CD), and several different mechanisms likely account for postoperative diarrhea in CD. A targeted strategy based on a comprehensive understanding of postoperative diarrhea is helpful for better postoperative recovery.

Body mass index change in adulthood and lung and upper aerodigestive tract cancers.

Body mass index (BMI) has been inversely associated with lung and upper aerodigestive tract (UADT) cancers. However, only a few studies have assessed BMI change in adulthood in relation to cancer. To understand the relationship between BMI change and these cancers in both men and women, we analyzed data from a population-based case-control study conducted in Los Angeles County. Adulthood BMI change was measured as the proportional change in BMI between age 21 and 1 year before interview or diagnosis. Five categories of BMI change were included, and individuals with no more than a 5% loss or gain were defined as having a stable BMI (reference group). Adjusted odds ratios (ORs) and their 95% confidence intervals (CIs) were estimated using logistic regression models. Potential confounders included age, gender, ethnicity, education, tobacco smoking and energy intake. For UADT cancers, we also adjusted for alcohol drinking status and frequency. A BMI gain of 25% or higher in adulthood was inversely associated with lung cancer (OR 0.53, 95% CI 0.33-0.84) and UADT cancers (OR 0.44, 95% CI 0.27-0.71). In subgroup analyses, a BMI gain of ≥25% was inversely associated with lung and UADT cancers among current and former smokers, as well as among current and former alcohol drinkers. The inverse association persisted among moderate and heavy smokers (≥20 pack-years). The observed inverse associations between adulthood BMI gain and lung and UADT cancers indicate a potential role for body weight-related biological pathways in the development of lung and UADT cancers.

Purification and characterization of antibacterial compounds of Pseudoalteromonas flavipulchra JG1.

Pseudoalteromonas flavipulchra JG1 produces a protein PfaP and a range of small-molecule compounds with inhibitory activities against Vibrio anguillarum. The PfaP protein was purified from the extracellular products of JG1 by electroelution, and antibacterial activity was observed by an in-gel antibacterial assay. The complete amino acid sequence (694 aa) of PfaP was determined by de novo peptide sequencing and subsequent alignment with the proteome sequence of strain JG1. The calculated molecular mass of PfaP was 77.0 kDa. PfaP was 58 % identical to l-lysine oxidase AlpP of Pseudoalteromonas tunicata D2, and 54 % identical to the marinocine antimicrobial protein of Marinomonas mediterranea MMB-1. Five small molecules (compounds 1-5) with antibacterial activity, which were identified as p-hydroxybenzoic acid (1), trans-cinnamic acid (2), 6-bromoindolyl-3-acetic acid (3), N-hydroxybenzoisoxazolone (4) and 2'-deoxyadenosine (5), were purified by sequential column chromatography over silica gel, Sephadex LH-20 and RP-18 from ethyl acetate extract of strain JG1, and their structures were determined by NMR and MS. Brown compound 3, the only brominated compound, showed antibacterial activity against both Gram-positive and Gram-negative bacteria.

Restricted intravenous fluid regimen reduces the rate of postoperative complications and alters immunological activity of elderly patients operated for abdominal cancer: a randomized prospective clinical trail.

BACKGROUND: Perioperative fluid restriction can lead to better clinical outcomes and reduced complications. However, whether perioperative fluid restriction can alter the patient's postoperative cellular immunity is unknown. Therefore, a randomized, prospective clinical study was designed to determine whether fluid restriction improves immunological outcome in elderly patients who undergo gastrointestinal surgery for cancer removal. METHODS: A total of 179 patients aged 65 years or older were recruited for the study and were randomly assigned to receive the restricted fluid regimen (R group) or the standard fluid regimen (S group). Postoperative T-lymphocyte subpopulations (CD3(+), CD4(+), and CD8(+)) frequencies and monocyte HLA-DR expression was investigated. Perioperative complications and cellular immunity changes were analyzed comparatively between the two groups. RESULTS: The restricted intravenous fluid regimen was associated with significantly less postoperative complications (1.5 complications/patient vs. S group: 2.2 complications/patient), especially for infection complications (15% vs. S group: 27%, p = 0.04). Circulating CD3(+) T-cells were suppressed after surgery in both treatment groups, but the cell frequency (cell/µL) was higher in the R group (746 vs. S group: 480 at postoperative day (POD) 2, p = 0.022; 878 vs. 502 at POD 3, p = 0.005; 892 vs. 674 at POD 5, p = 0.042). Similarly, the HLA-DR expression (% of all T cells) in monocytes were decreased in both groups, but the expression remained higher in the R group (66.20 vs. S group: 51.97 at POD 1, p = 0.029; 68.19 vs. 51.26 at POD 2, p = 0.039; 72.19 vs. 57.45 at POD 3, p = 0.014; 73.92 vs. 60.46 at POD 5, p = 0.036). Multivariate analysis suggested that perioperative CD3(+) T cell changes were associated with the development of postoperative complications [odds ratio (OR) = 1.963; 95% confidence interval (CI) 1.019-3.782; p = 0.044] and postoperative infections (OR = 3.106; 95% CI 1.302-7.406; p = 0.011). CONCLUSIONS: In elderly gastrointestinal cancer patients, cellular immunity is better preserved by the perioperative fluid restriction regimen. The better preserved cellular immunological function is correlated with a reduced perioperative complications rate.

Redetermined structure of oxaline: absolute configuration using Cu Kα radiation.

In the title compound, C(24)H(25)N(5)O(4), the stereogenic C atom bonded to three N atoms and one C atom has an S configuration and its directly bonded neighbour has an R configuration. An intra-molecular N-H⋯O hydrogen bond supports the near coplanarity of the two C(3)N(2)-five-membered rings [dihedral angle = 5.64 (10)°]. In the crystal, mol-ecules are linked by N-H⋯N hydrogen bonds, forming a C(8) chain propagating in [001]. The chains are connected by C-H⋯O inter-actions, generating a three-dimensional network. The previous study [Nagel et al. (1974 ▶). Chem. Commun. pp. 1021-1022] did not establish the absolute structure and no atomic coordinates were published or deposited.

[Outcomes of chronic radiation intestinal injury treated with surgical interventions].

OBJECTIVE: To explore the surgical approaches and clinical outcomes of chronic radiation intestinal injury (CRII). METHODS: From January 1, 2001 to December 31, 2010, at Department of Surgery, Nanjing General Hospital of Nanjing Command a consecutive series of 206 CRII patients undergoing surgical interventions was reviewed retrospectively. There were 64 males and 142 females with an age range of (50 ± 11) years old. The indications, surgical approaches, surgical complications and mortality were analyzed. RESULTS: 206 CRII patients received 229 surgical treatment, 31 patients underwent two or more operations. The course of surgical interventions included intestinal obstruction (n = 142), intestinal fistula (n = 56), proctitis (n = 12), bleeding (n = 6) and others (n = 13). They underwent 229 laparotomies including intestinal resection and primary anastomosis (n = 142), intestinal resection and enterostomy (n = 57), exclusion of radiation-related gastrointestinal diseases (n = 14) and other procedures (n = 16). The occurrence rate of postoperative intestinal complications was 25.7% (53/206). Five patients (2.4%) died within the postoperative 28 days. CONCLUSION: Surgery is often required for patients with chronic radiation-induced intestinal obstruction, fistula, hemorrhage and perforation, etc. Resection and primary anastomosis with undamaged segments may be performed safely in selected patients. And a judicious use of stoma can reduce the rates of major surgical mortality and morbidity.

[Impact of disease activity on postoperative recurrence and complications after bowel resection for Crohn's disease].

OBJECTIVE: To determine whether the perioperative disease activity is associated with recurrence and complications after bowel resection for Crohn's disease (CD). METHODS: Clinical data of patients underwent bowel resection for CD at the Nanjing General Hospital of Nanjing Military Command from January 2002 to January 2011 was retrospectively analyzed. Postoperative recurrence and complications in patients with active disease were compared with those in patients with remission. RESULTS: A total of 90 patients underwent bowel resection for CD, active disease were seen in 43 patients at the time of surgery, while the rest 47 patients were in remission. The postoperative cumulative endoscopic recurrence rate was 8.5% at 1 year, 27.7% at 2 years and 44.7% at 3 years in the patients with remission, and was 27.9% at 1 year, 37.2% at 2 years and 53.5% at 3 years in patients with active disease. Data indicated the endoscopic recurrence were statistically significant in the first year after surgery (χ² = 4.605, P = 0.032). Additional, the postoperative complication rates in patients with remission (14.9%) was significantly lower than that in patients with active disease (51.2%) (χ² = 6.979, P < 0.001). CONCLUSION: Patients with active disease at the time of surgery were encountered with early postoperative recurrence and increased complications after intestinal resection for CD.

[Novel surgery for refractory mixed constipation: analysis of the technical notes and outcome to Jinling procedure].

OBJECTIVE: To discuss a new surgical strategy: Jinling procedure (subtotal colectomy combined with modified Duhamel procedure), of which the indications, technical notes and outcomes were analyzed. METHODS: The 590 patients with refractory slow-transit constipation associated with outlet obstruction was strictly included between February 2000 and December 2011. The patients included 103 males and 487 females. Their age were 14-75 years (average 42 ± 13). The 412 patients received laparoscopic-assistant Jinling procedure, and 178 patients with open Jinling procedure. The pre- and post-operation data were collected. The follow up rate were 100%, 98.1%, 95.8% and 92.7% at 3, 6, 12 and 24 months. RESULTS: There was no surgery-related death. Mean hospital day was (12 ± 9) days. Most complications were managed conservatively without significant events. The common complications after surgery were adhesive intestinal obstruction (9.2%), anastomosis bleeding (8.1%) and anastomosis leakage (2.9%). The gastrointestinal quality of life index score was 72 ± 9 preoperatively and increased to 68 ± 11, 99 ± 6, 105 ± 9, 106 ± 9 at 3, 6, 12 and 24 month follow-up, respectively (t = 62.1, -25.1, -126.5, -143.2, P < 0.01). The Wexner constipation scale was 21.9 ± 4.5 preoperatively and decreased to 9.6 ± 2.4, 5.9 ± 2.1, 4.6 ± 1.9, 4.5 ± 1.8 at 3, 6, 12 and 24 month follow-up, respectively (t = 48.6, 61.8, 58.2, 45.9, P < 0.01). The satisfactory rate was 77.5%, 92.1%, 93.0% and 94.1% at 3, 6, 12, and 24 month follow-up. CONCLUSIONS: Jinling procedure provides a good surgical option for refractory slow-transit constipation associated with outlet obstruction.

Current status of novel biologics and small molecule drugs in the individualized treatment of inflammatory bowel disease.

Treatment strategies for inflammatory bowel disease (IBD) are rapidly evolving with the development of biologics and small molecule drugs (SMDs). However, these drugs are not guaranteed to be effective in all patients, and a "ceiling effect" of biologic monotherapy may occur. This issue highlights an unmet need for optimizing the use of biologics and predicting therapeutic responses. Thus, the development of new drugs with novel mechanisms of action is urgently needed for patients with primary nonresponse and secondary loss of response to conventional biologics and SMDs. In addition, combining different biologics or SMDs has been proposed as a novel strategy to enhance treatment efficacy in IBD, which theoretically has multidimensional anti-inflammatory potential. Based on the current evidence available for IBD, dual targeted therapy may be a promising strategy for refractory IBD patients who have failed in multiple biologic trea-tments or who have extraintestinal manifestation. Additionally, identifying the subgroup of IBD patients who are responding to biological combination therapies is also equally important in stable disease remission. In this review, we sum-marize the newly developed biologics and SMDs and the current status of bio-logics/SMDs to highlight the development of individualized treatment in IBD.

Perforating and nonperforating indications in repeated surgeries for Crohn's disease.

BACKGROUND: Despite advances in medical therapy for Crohn's disease (CD), most patients with CD require repeated resection surgeries. AIM: To analyze the perforating and nonperforating indications of repeated CD operations and identify the anastomosis characteristics for postoperative CD. METHODS: We retrospectively reviewed 386 patients who underwent at least one resection for CD between 2003 and 2013.Clinical characteristics of each surgery were collected. Univariate and multivariate analyses were performed to determine risk factors for recurrence. RESULTS: The indication for reoperation in CD tends to be the same as that for primary operation, i.e., perforating disease tends to represent as perforating disease and nonperforating as nonperforating. Concordance was found between the first surgery and second surgery in terms of the indication for the operation (P = 0.006), and the indication for the third surgery was also correlated with that for the second surgery (P = 0.033). Even if the correlation of surgical indications between repeated operations, the rate of perforating indication for the second and third surgeries was significantly higher than that of the first surgery. In addition, the presence of perforating CD was a predictor of recurrence for both the first and second surgeries. Moreover, anastomotic lesions were the most common sites of recurrence after the operation. Based on the importance of anastomosis, anastomosis might be a new type of disease location for the classification of postoperative CD. CONCLUSION: CD not only has stable characteristics but also progresses chronically. Perforation is a progressive surgical indication for Crohn's disease. For CD after surgery, anastomosis may be a new classification of disease location.

Risk Factors for Worsening of Bone Loss in Patients Newly Diagnosed with Inflammatory Bowel Disease.

Background: Bone loss is common in patients with inflammatory bowel disease (IBD). The aim of the present study was to determine the prevalence of metabolic bone disease in patients newly diagnosed with IBD and to identify the risk factors for bone loss over time. Methods: We performed a retrospective, both cross-sectional and longitudinal, study to extract the risk factors of bone loss (including osteopenia and osteoporosis) in patients newly diagnosed with IBD, using dual-energy X-ray absorptiometry (DXA). Results: A total of 639 patients newly diagnosed with IBD that had at least one DXA were included in the cross-sectional study. Osteopenia and osteoporosis were diagnosed in 24.6% and 5.4% of patients, respectively. Age at diagnosis, body mass index, and serum phosphorus were identified as independent factors associated with bone loss at baseline. A total of 380 of the 639 IBD patients (including 212 CD patients and 168 UC patients) with at least a second DXA scan were included in the longitudinal study. 42.6% of the patients presented a worsening of bone loss in the follow-up study. Menopause, albumin, and use of corticosteroids were identified as independent factors associated with worsening of bone loss. Conclusions: Metabolic bone disease is common in IBD patients, and there is a significant increase in prevalence of bone loss over time. Postmenopausal female, malnourished patients, and those requiring corticosteroid treatment are at risk for persistent bone loss. Therefore, BMD measurements and early intervention with supplementation of calcium and vitamin D are recommended in IBD patients with high-risk factors.

(22E,24R)-3ß,5α,9α-Trihy-droxy-ergosta-7,22-dien-6-one monohydrate.

The title ergosterol compound, C(28)H(44)O(4)·H(2)O, is composed of four fused rings (three six-membered and one five-membered) and a side chain. It is a derivative of ergosterol and was isolated from a marine-derived halotolerant fungus, Cladosporium cladosporioides PXP-49. In the crystal, mol-ecules are assembled by classical O-H⋯O hydrogen bonds, forming a two-dimensional network, with base vectors [100] and [010]. The absolute configuration was assigned from the measured optical rotation and reference to the literature. An intra-molecular O-H⋯O hydrogen bond occurs.

Role of mesenteric component in Crohn's disease: A friend or foe?

Crohn's disease (CD) is a complex and relapsing gastrointestinal disease with mesenteric alterations. The mesenteric neural, vascular, and endocrine systems actively take part in the gut dysbiosis-adaptive immunity-mesentery-body axis, and this axis has been proven to be bidirectional. The abnormalities of morphology and function of the mesenteric component are associated with intestinal inflammation and disease progress of CD via responses to afferent signals, neuropeptides, lymphatic drainage, adipokines, and functional cytokines. The hypertrophy of mesenteric adipose tissue plays important roles in the pathogenesis of CD by secreting large amounts of adipokines and representing a rich source of proinflammatory or profibrotic cytokines. The vascular alteration, including angiogenesis and lymphangiogenesis, is concomitant in the disease course of CD. Of note, the enlarged and obstructed lymphatic vessels, which have been described in CD patients, are likely related to the early onset submucosa edema and being a cause of CD. The function of mesenteric lymphatics is influenced by endocrine of mesenteric nerves and adipocytes. Meanwhile, the structure of the mesenteric lymphatic vessels in hypertrophic mesenteric adipose tissue is mispatterned and ruptured, which can lead to lymph leakage. Leaky lymph factors can in turn stimulate adipose tissue to proliferate and effectively elicit an immune response. The identification of the role of mesentery and the crosstalk between mesenteric tissues in intestinal inflammation may shed light on understanding the underlying mechanism of CD and help explore new therapeutic targets.