Machine learning in predicting T-score in the Oxford classification system of IgA nephropathy.

Background: Immunoglobulin A nephropathy (IgAN) is one of the leading causes of end-stage kidney disease (ESKD). Many studies have shown the significance of pathological manifestations in predicting the outcome of patients with IgAN, especially T-score of Oxford classification. Evaluating prognosis may be hampered in patients without renal biopsy. Methods: A baseline dataset of 690 patients with IgAN and an independent follow-up dataset of 1,168 patients were used as training and testing sets to develop the pathology T-score prediction (T pre) model based on the stacking algorithm, respectively. The 5-year ESKD prediction models using clinical variables (base model), clinical variables and real pathological T-score (base model plus T bio), and clinical variables and T pre (base model plus T pre) were developed separately in 1,168 patients with regular follow-up to evaluate whether T pre could assist in predicting ESKD. In addition, an external validation set consisting of 355 patients was used to evaluate the performance of the 5-year ESKD prediction model using T pre. Results: The features selected by AUCRF for the T pre model included age, systolic arterial pressure, diastolic arterial pressure, proteinuria, eGFR, serum IgA, and uric acid. The AUC of the T pre was 0.82 (95% CI: 0.80-0.85) in an independent testing set. For the 5-year ESKD prediction model, the AUC of the base model was 0.86 (95% CI: 0.75-0.97). When the T bio was added to the base model, there was an increase in AUC [from 0.86 (95% CI: 0.75-0.97) to 0.92 (95% CI: 0.85-0.98); P = 0.03]. There was no difference in AUC between the base model plus T pre and the base model plus T bio [0.90 (95% CI: 0.82-0.99) vs. 0.92 (95% CI: 0.85-0.98), P = 0.52]. The AUC of the 5-year ESKD prediction model using T pre was 0.93 (95% CI: 0.87-0.99) in the external validation set. Conclusion: A pathology T-score prediction (T pre) model using routine clinical characteristics was constructed, which could predict the pathological severity and assist clinicians to predict the prognosis of IgAN patients lacking kidney pathology scores.

Preoperative pancreatic CT value is related to pancreatic fistula after pancreaticoduodenectomy: a retrospective study.

Background: Pancreatic fistula (PF) is the main complication in patients undergoing pancreaticoduodenectomy. Computed tomography (CT) value can reflect pancreatic tissue characteristics which is related to PF. This study was designed to study the relationship between the preoperative CT value and pancreatic fistula. Methods: We retrospectively reviewed the clinical and medical data of patients undergoing pancreaticoduodenectomy from 2017 to 2021. The pancreatic CT value and the CT value ratios of the pancreas and abdominal aorta (PCT/ACT) were measured and compared between the PF group and non-PF group. The values in different PF severity groups were compared using variance analysis. A cut-off value was selected by receiver operating characteristic (ROC) curve. Single-factor and multiple-factor analysis were performed to evaluate Correlation between PF and CT. Results: One hundred and twenty-seven cases were included in this study. The PCT/ACT in the PF group was significantly lower than that in the non-PF group (P<0.001), and the PCT/ACT value was correlatively lower in the severe PF group than in the mild PF group (P=0.008). A cutoff value of 0.99 was selected by ROC curves analysis. Further multifactor analysis identified PCT/ACT <0.99 to be an independent preoperative predictor [odds ratio (OR): 11.3, P<0.01]. Conclusions: The preoperative pancreatic CT value can indirectly reflect the histological condition of the pancreas and thus may related to postoperative PF after pancreaticoduodenectomy and provide useful information for surgeons in deciding upon the pancreaticojejunostomy method.

PD-L1 Enhanced by cis-Urocanic Acid on Langerhans Cells Inhibits Vγ4+ γδT17 Cells in Imiquimod-Induced Skin Inflammation.

Psoriasis is an IL-23/IL-17-mediated inflammatory autoimmune dermatosis, and UVB may contribute to immunosuppression and ameliorate associated symptoms. One of the pathophysiology underlying UVB therapy is the production of cis-urocanic acid (cis-UCA) by keratinocytes. However, the detailed mechanism is yet to be fully understood. In this study, we found FLG expression and serum cis-UCA levels were significantly lower in patients with psoriasis than in healthy controls. We also noted that cis-UCA application inhibited psoriasiform inflammation through the reduction of Vγ4+ γδT17 cells in murine skin and draining lymph nodes. Meanwhile, CCR6 was downregulated on γδT17 cells, which would suppress the inflammatory reaction at a distal skin site. We revealed that the 5-hydroxytryptamine receptor 2A, the known cis-UCA receptor, was highly expressed on Langerhans cells in the skin. cis-UCA also inhibited IL-23 expression and induced PD-L1 on Langerhans cells, leading to the attenuated proliferation and migration of γδT-cells. Compared to the isotype control, α-PD-L1 treatment in vivo could reverse the antipsoriatic effects of cis-UCA. PD-L1 expression on Langerhans cells was sustained through the cis-UCA-induced mitogen-activated protein kinase/extracellular signal-regulated kinase pathway. These findings uncover the cis-UCA-induced PD-L1-mediated immunosuppression on Langerhans cells, which facilitates the resolution of inflammatory dermatoses.

Potential factors affecting success rate and long term outcome in single balloon enteroscopy-assisted therapeutic endoscopic retrograde cholangiopancreatography in patients with pancreaticojejunal anastomotic stenosis: a retrospective study.

Background: Pancreaticojejunal anastomotic stenosis (PJS) after pancreaticoduodenectomy (PD) is difficult to treat. Single-balloon enteroscope-assisted endoscopic retrograde pancreatography (SBE-assisted ERP) is a safe way to treat PJS with the strength of minimally invasion and repeatability, but since its technical difficulty and few patient number, data on long-term outcomes remain limited. The optimal treatment is still unknown. We aim to study the safety, effectiveness, and long-term outcome of single balloon enteroscopy-assisted (SBE-assisted) therapeutic ERP in patients with PJS in this study. Methods: The clinical information of patients undergoing SBE-assisted therapeutic ERP from March 2016 to March 2021 were retrospectively analyzed. All patients were diagnosed as PJS and without any contraindication for therapeutic endoscopy. Treatment details, postoperative complications, factors influencing technical success rate were evaluated. Long-term outcomes results were obtained by clinical or telephone follow-up. Results: Sixteen patients with median age of 51 years were included in this study, surgical reconstruction methods including PD with Whipple reconstruction, PD with Child reconstruction, pylorus-preserving pancreaticoduodenectomy (PpPD) with Whipple reconstruction. Eight patients were successfully treated. No serious complications happened. Risk factors for the failure of pancreaticojejunal anastomotic site identification include the digestive tract reconstruction sequence, pancreaticojejunostomy method, pancreatic duct tube implantation, pancreatic duct width before surgery, and pancreatic fistula during perioperative period. The median follow-up time was 77.2 months, the mean indwelling time of the stent was 62.3 months [interquartile range (IQR), 6.8-153.7 months]. Two of eight patients developed recurrent PJS. The variation in body mass index (BMI) was +2.46 in the non-recurrence group compared to -1.09 in the recurrence group and -2.12 in the endoscopic retrograde cholangiopancreatography (ERCP) treatment failure group. Conclusions: ERP intervention should be carried out early once PJS occurs in order to increase success rate. BMI is a crucial indicator which can reflex PJS rehabilitation degree during follow-up. In order to reduce PJS recurrence rate, a wider pancreatic stent and a longer stent indwelling time are recommended.

Fibrinogen promotes gallbladder cancer cell metastasis and extravasation by inducing ICAM1 expression.

Fibrinogen plays an important role in tumor progression. Here, we explored the role of fibrinogen in gallbladder cancer (GBC) metastasis. The plasma fibrinogen level in M1 GBC patients was higher than in M0 GBC patients, indicating that fibrinogen may participate in GBC metastasis. Treatment of GBC cell lines with fibrinogen promoted metastasis and induced the expression of intercellular adhesion molecule 1 (ICAM1). ICAM1 overexpression promoted metastasis and knockdown inhibited it. The cell adhesion and transendothelial migration of GBC cells were enhanced by fibrinogen treatment and ICAM1 overexpression. In addition, the medium of fibrinogen-treated and overexpression-ICAM1 NOZ cells exhibited enhanced macrophages recruitment. This may work in concert to promote angiogenesis. Immunohistochemistry results on clinical specimens showed that higher fibrinogen levels, higher ICAM1 expression, higher blood vessel density, and higher macrophage levels were present simultaneously. Collectively, this study indicates fibrinogen promotes metastasis and extravasation by inducing ICAM1 expression to enhance tumor cell migration, cell adhesion, transendothelial migration and promote angiogenesis and increase vascular endothelial permeability.

The Combination of a Novel GLUT1 Inhibitor and Cisplatin Synergistically Inhibits Breast Cancer Cell Growth By Enhancing the DNA Damaging Effect and Modulating the Akt/mTOR and MAPK Signaling Pathways.

Breast cancer is the most prevalent cancer and the second leading cause of cancer death in women. Cisplatin is a commonly used chemotherapeutic drug for breast cancer treatment. Owing to serious side effects, the combination of cisplatin with other drugs is an effective strategy to simultaneously reduce side effects and increase the anticancer efficacy. GLUT1 is an emerging target for cancer treatment since cancer cells usually consume more glucose, a phenomenon called the Warburg effect. In this study, we found that the combination of cisplatin and a novel GLUT1 inhibitor #43 identified from our previous high-throughput screening exerted a synergistic anticancer effect in MCF-7 and MDA-MB-231 breast cancer cells. Mechanism studies in MCF-7 cells revealed that combination of cisplatin and #43 significantly induced apoptosis, intracellular reactive oxygen species, and loss of mitochondrial membrane potential. Furthermore, #43 enhanced the DNA damaging effect of cisplatin. Akt/mTOR downstream signaling and the ERK signaling pathway usually involved in cell growth and survival were inhibited by the combination treatment. On the other hand, phosphorylation of p38 and JNK, which may be associated with apoptosis, was induced by the combination treatment. Altogether, our data indicate that oxidative stress, DNA damage, the Akt/mTOR and MAPK signaling pathways, and apoptosis may be involved in the synergism of cisplatin and #43 in breast cancer cells.

Development and Validation of a Prognostic Nomogram Based on the Systemic Immune-Inflammation Index for Resectable Gallbladder Cancer to Predict Survival and Chemotherapy Benefit.

OBJECTIVES: To investigate the prognostic significance of the systemic immune-inflammation index (SII) in patients after radical cholecystectomy for gallbladder cancer (GBC) using overall survival (OS) as the primary outcome measure. METHODS: Based on data from a multi-institutional registry of patients with GBC, significant prognostic factors after radical cholecystectomy were identified by multivariate Cox proportional hazards model. A novel staging system was established, visualized as a nomogram. The response to adjuvant chemotherapy was compared between patients in different subgroups according to the novel staging system. RESULTS: Of the 1072 GBC patients enrolled, 691 was randomly selected in the discovery cohort and 381 in the validation cohort. SII>510 was found to be an independent predictor of OS (hazard ratio [HR] 1.90, 95% confidence interval [CI] 1.42-2.54). Carbohydrate antigen 199(CA19-9), tumor differentiation, T stage, N stage, margin status and SII were involved in the nomogram. The nomogram showed a superior prediction compared with models without SII (1-, 3-, 5-year integrated discrimination improvement (IDI):2.4%, 4.1%, 5.4%, P<0.001), and compared to TNM staging system (1-, 3-, 5-year integrated discrimination improvement (IDI):5.9%, 10.4%, 12.2%, P<0.001). The C-index of the nomogram in predicting OS was 0.735 (95% CI 0.683-0.766). The novel staging system based on the nomogram showed good discriminative ability for patients with T2 or T3 staging and with negative lymph nodes after R0 resection. Adjuvant chemotherapy offered significant survival benefits to these patients with poor prognosis. CONCLUSIONS: SII was an independent predictor of OS in patients after radical cholecystectomy for GBC. The new staging system identified subgroups of patients with T2 or T3 GBC with negative lymph nodes who benefited from adjuvant chemotherapy. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, identifier (NCT04140552).

Efficacy and safety of ciprofol for the sedation/anesthesia in patients undergoing colonoscopy: Phase IIa and IIb multi-center clinical trials.

OBJECTIVE: Ciprofol is a new intravenous anesthetic agent similar to propofol that has the pharmacodynamic characteristics of a rapid rate of onset and recovery in pre-clinical experiments. The aims of the present clinical trials were to compare the efficacy and safety of ciprofol emulsion for sedation or general anesthesia during colonoscopy and to define optimal doses for a subsequent phase III clinical trial. METHODS: A phase IIa multi-center, open-label, non-randomized, positive control, dose-escalating study was performed to determine a recommended phase IIb dose (RP2D) of ciprofol to induce sedation or anesthesia in patients undergoing colonoscopy. Phase IIb was also a multi-center clinical trial, but the patients were randomized into 3 groups at a ratio of 1:1:1. It was a double-blinded, propofol controlled study that administered ciprofol 0.4 mg/kg (n = 31) and 0.5 mg/kg (n = 32) or propofol at 2.0 mg/kg (n = 31), with the aim of establishing the optimal dose of ciprofol. The primary endpoint was the colonoscopy success rate. Secondary endpoints were the duration of colonoscope insertion, recovery time, number of top-up doses needed, and the total dose of ciprofol or propofol required to maintain adequate sedation or anesthesia. In addition, we evaluated the satisfaction of sedation/anesthesia from the endoscopists, anesthetists and patients' points of view. Safety was assessed according to the incidence of AEs including serious AEs and drug related AEs and the assessment of vital signs, a 12-lead ECG and laboratory tests. RESULTS: In the phase IIa trial, the colonoscopy success rates in the 0.2-0.5 mg/kg ciprofol and propofol 2.0 mg/kg groups were 100% and all doses were safe and well tolerated. Ciprofol doses of 0.4 mg/kg and 0.5 mg/kg are recommended for subsequent IIb phases. In the phase IIb trial, a 100% success rate was reconfirmed in all the dosage groups. The mean time of colonoscope insertion in the ciprofol 0.4 mg/kg, ciprofol 0.5 mg/kg and propofol 2.0 mg/kg groups were 1.9, 1.5 and 1.5 min, the mean recovery times from colonoscope withdrawal were 6.1, 5.1, and 4.3 min, and the times to discharge were 11.8, 11.2 and 10.6 min, respectively. The satisfaction ratings of anesthetists in the ciprofol 0.5 mg/kg group (9.5 ± 0.8) were higher than in the ciprofol 0.4 mg/kg (9.2 ± 1.0) and propofol 2.0 mg/kg (9.2 ± 0.9) groups. The incidence of sedation and anesthesia-related AEs was highest in the propofol 2.0 mg/kg group (25.8%), followed by the ciprofol 0.5 mg/kg group (21.9%), and was least in the ciprofol 0.4 mg/kg group (16.1%) (P = 0.750). CONCLUSIONS: Ciprofol was safe and well tolerated at doses ranging from 0.1 mg/kg to 0.5 mg/kg. Ciprofol 0.4-0.5 mg/kg induced equivalent sedation/anesthesia and had a similar safety profile to propofol 2.0 mg/kg during colonoscopy without producing serious AEs.

Neuropathic Itch.

Neurologic insults as varied as inflammation, stroke, and fibromyalgia elicit neuropathic pain and itch. Noxious sensation results when aberrantly increased afferent signaling reaches percept-forming cortical neurons and can occur due to increased sensory signaling, decreased inhibitory signaling, or a combination of both processes. To treat these symptoms, detailed knowledge of sensory transmission, from innervated end organ to cortex, is required. Molecular, genetic, and behavioral dissection of itch in animals and patients has improved understanding of the receptors, cells, and circuits involved. In this review, we will discuss neuropathic itch with a focus on the itch-specific circuit.

Usefulness of pre-operative endoscopic retrograde cholangiopancreatography in diagnosis and management of forme fruste choledochal cyst in children.

BACKGROUND: Forme fruste choledochal cyst (FFCC), characterized by a minimally dilated common bile duct (CBD) and associated pancreaticobiliary maljunction (PBM), is difficult to diagnose in a timely manner in clinical practice. However, endoscopic retrograde cholangiopancreatography (ERCP) can clearly delineate CBD and PBM. Hence, we evaluated the value of ERCP in the diagnosis and management of FFCC. METHODS: The medical records of patients diagnosed with FFCC were retrospectively reviewed. From January 2003 to December 2010, patients underwent surgery without ERCP (non-ERCP group); from January 2011, all patients underwent pre-operative ERCP (ERCP group). Demographics, laboratory results, perioperative data and post-operative complications were compared between the two groups. RESULTS: There were 24 patients in the ERCP group and 11 in the non-ERCP group. Laboratory data improved to a greater extent after ERCP. ERCP was superior to both magnetic resonance cholangiopancreatography and ultrasonography in delineating CBD and PBM. In the ERCP group, 20 of the 24 patients were noted to have filling defects in the biliary tract and underwent pre-operative endoscopic sphincterotomy. Intra-operative blood loss was lower and transfusion less frequent in the ERCP group (P < 0.05). There were no ERCP-related complications. CONCLUSIONS: ERCP can accurately delineate the minimal CBD dilatation, associated pancreaticobiliary tract abnormalities and PBM of FFCC. ERCP can improve the perioperative and post-operative results of paediatric patients with FFCC.

The Combination of MK-2206 and WZB117 Exerts a Synergistic Cytotoxic Effect Against Breast Cancer Cells.

Breast cancer is the most commonly diagnosed cancer and the second leading cause of cancer death in women. Hormone receptor-positive breast cancer is usually subjected to hormone therapy, while triple-negative breast cancer is more formidable and poses a therapeutic challenge. Glucose transporters are potential targets for the development of anticancer drugs. In search of anticancer agents whose effect could be enhanced by a GLUT1 inhibitor WZB117, we found that MK-2206, a potent allosteric Akt inhibitor, when combined with WZB117, showed a synergistic effect on growth inhibition and apoptosis induction in breast cancer cells, including ER(+) MCF-7 cells and triple-negative MDA-MB-231 cells. The combination index values at 50% growth inhibition were 0.45 and 0.21, respectively. Mechanism studies revealed that MK-2206 and WZB117 exert a synergistic cytotoxic effect in both MCF-7 and MDA-MB-231 breast cancer cells by inhibiting Akt phosphorylation and inducing DNA damage. The combination may also compromise DNA damage repair and ultimately lead to apoptosis. Our findings suggest that the combination of Akt inhibitors and GLUT1 inhibitors could be a novel strategy to combat breast cancer.

Application of single balloon enteroscopy-assisted therapeutic endoscopic retrograde cholangiopancreatography in patients after bilioenteric Roux-en-Y anastomosis: Experience of multi-disciplinary collaboration.

BACKGROUND: Bilioenteric Roux-en-Y anastomosis is one of the most complicated approaches for reconstructing the gastrointestinal tract, and endoscopic retrograde cholangiopancreatography (ERCP) is technically challenging in patients after bilioenteric Roux-en-Y anastomosis. The optimal endoscopic strategies for such cases remain unknown. AIM: To explore the feasibility and effectiveness of single balloon enteroscopy-assisted (SBE-assisted) therapeutic ERCP in patients after bilioenteric Roux-en-Y anastomosis based on multi-disciplinary collaboration between endoscopists and surgeons as well as report the experience from China. METHODS: This is a single center retrospective study. All of the SBE-assisted therapeutic ERCP procedures were performed by the collaboration between endoscopists and surgeons. The operation time, success rate, and complication rate were calculated. RESULTS: Forty-six patients received a total of 64 SBE-assisted therapeutic ERCP procedures, with successful scope intubation in 60 (93.8%) cases and successful diagnosis in 59 (92.2%). All successfully diagnosed cases received successful therapy. None of the cases had perforation or bleeding during or after operation, and no post-ERCP pancreatitis occurred. CONCLUSION: Based on multi-disciplinary collaboration, SBE-assisted therapeutic ERCP in patients after bilioenteric Roux-en-Y anastomosis is relatively safe and effective and has a high success rate.

Lasting effects of general anesthetics on the brain in the young and elderly: "mixed picture" of neurotoxicity, neuroprotection and cognitive impairment.

General anesthetics are commonly used in major surgery. To achieve the depth of anesthesia for surgery, patients are being subjected to a variety of general anesthetics, alone or in combination. It has been long held an illusory concept that the general anesthesia is entirely reversible and that the central nervous system is returned to its pristine state once the anesthetic agent is eliminated from the active site. However, studies indicate that perturbation of the normal functioning of these targets may result in long-lasting desirable or undesirable effects. This review focuses on the impact of general anesthetic exposure to the brain and summarizes the molecular and cellular mechanisms by which general anesthetics may induce long-lasting undesirable effects when exposed at the developing stage of the brain. The vulnerability of aging brain to general anesthetics, specifically in the context of cognitive disorders and Alzheimer's disease pathogeneses are also discussed. Moreover, we will review emerging evidence regarding the neuroprotective property of xenon and anesthetic adjuvant dexmedetomidine in the immature and mature brains. In conclusion, "mixed picture" effects of general anesthetics should be well acknowledged and should be implemented into daily clinical practice for better patient outcome.

Dihydroartemisinin-Bile Acid Hybridization as an Effective Approach to Enhance Dihydroartemisinin Anticancer Activity.

A series of hybrid compounds based on natural products-bile acids and dihydroartemisinin-were prepared by different synthetic methodologies and investigated for their in vitro biological activity against HL-60 leukemia and HepG2 hepatocellular carcinoma cell lines. Most of these hybrids presented significantly improved antiproliferative activities with respect to dihydroartemisinin and the parent bile acid. The two most potent hybrids of the series exhibited a 10.5- and 15.4-fold increase in cytotoxic activity respect to dihydroartemisinin alone in HL-60 and HepG2 cells, respectively. Strong evidence that an ursodeoxycholic acid hybrid induced apoptosis was obtained by flow cytometric analysis and western blot analysis.

Traditional Chinese Medicine as a Remedy for Male Infertility: A Review.

Male infertility (MI) is a complex multifactorial disease, and idiopathic infertility accounts for 30% of cases of MI. At present, the evidence for the effectiveness of empirical drugs is limited, and in vitro fertilization is costly and may increase the risk of birth defects and childhood cancers. Therefore, affected individuals may feel obliged to pursue natural remedies. Traditional Chinese medicine (TCM) may represent a useful option for infertile men. It has been demonstrated that TCM can regulate the hypothalamic-pituitary-testicular axis and boost the function of Sertoli cells and Leydig cells. TCM can also alleviate inflammation, prevent oxidative stress, reduce the DNA fragmentation index, and modulate the proliferation and apoptosis of germ cells. Furthermore, TCM can supply trace elements and vitamins, ameliorate the microcirculation of the testis, decrease the levels of serum anti-sperm antibody, and modify epigenetic markers. However, the evidence in favor of TCM is not compelling, which has hindered the development of TCM. This review attempts to elucidate the underlying therapeutic mechanisms of TCM. We also explore the advantages of TCM, differences between TCM and Western medicine, and problems in existing studies. Subsequently, we propose solutions to these problems and present perspectives for the future development of TCM.

Dexmedetomidine attenuates spinal cord ischemia-reperfusion injury through both anti-inflammation and anti-apoptosis mechanisms in rabbits.

BACKGROUND: Dexmedetomidine (Dex) can improve neuronal viability and protect the spinal cord from ischemia-reperfusion (I/R) injury, but the underlying mechanisms are not fully understood. This study investigated the effects of dexmedetomidine on the toll-like receptor 4 (TLR4)-mediated nuclear factor κB (NF-κB) inflammatory system and caspase-3 dependent apoptosis induced by spinal cord ischemia-reperfusion injury. METHODS: Twenty-four rabbits were divided into three groups: I/R, Dex (10 µg/kg/h prior to ischemia until reperfusion), and Sham. Abdominal aortic occlusion was carried out for 30 min in the I/R and Dex groups. Hindlimb motor function was assessed using the Tarlov scoring system for gait evaluation. Motor neuron survival and apoptosis in the ventral grey matter were assessed by haematoxylin-eosin staining and terminal deoxynucleotidyl transferase-mediated dUTP biotin nick end labelling staining. The expression and localisation of ionised calcium-binding adaptor molecule 1, TLR4, NF-κB and caspase-3 were assessed by immunoreactivity analysis. The levels of interleukin 1ß and tumour necrosis factor α were assessed using enzyme-linked immunosorbent assays. RESULTS: Perioperative treatment with dexmedetomidine was associated with a significant preservation of locomotor function following spinal cord ischemia-reperfusion injury with increased neuronal survival in the spinal cord compared to control. In addition, dexmedetomidine suppressed microglial activation, inhibited the TLR4-mediated NF-κB signalling pathway, and inhibited the caspase-3 dependent apoptosis. CONCLUSIONS: Dexmedetomidine confers neuroprotection against spinal cord ischemia-reperfusion injury through suppression of spinal cord inflammation and neuronal apoptosis. A reduction in microglial activation and inhibition of both the TLR4-mediated NF-κB signalling pathway and caspase-3 dependent apoptosis are implicated.

Mechanistic insight into the relationship between triacylglycerol and crystallization of lipase-catalyzed interesterified blend of palm stearin and vegetable oil.

To give a deep insight into the relationship between triacylglycerol and crystallization of interesterified fat, the blends of palm stearin and various vegetable oil were catalyzed by two different immobilized lipases in this study. After interesterification, the blends had wider plastic range indicated by the SFC results and more ß' crystal. The improved physicochemical characteristics of interesterified blends were attributed to their changed TAG profiles. The statistical analysis showed that the interesterified blends were more likely to form ß' crystal with the increase of SU2-type TAG content and the decrease of SSS-type TAG content (p < 0.01). In addition, the decrease of ECN 42- and ECN 48-type TAGs and the increase of ECN 50-type TAGs also significantly enhanced the formation of ß' crystal (p < 0.05). Furthermore, the sn-1,3-specific Lipozyme TL IM-catalyzed interesterified blends were favorable for the formation of ß' crystal than the non-specific Novozym 435-catalyzed interesterified blends.

Emulsified isoflurane induces release of cytochrome C in human neuroblastoma SHSY-5Y cells via JNK (c-Jun N-terminal kinases) signaling pathway.

A large number of studies have demonstrated that inhalation anesthetic isoflurane induced neural cell death by apoptosis in various cell and animal models. Emulsified isoflurane (EIso) is a new type of intravenous preparation of isoflurane that attracts increasing research attention as a promising clinical agent due to its both advantages as an intravenous and inhalation anesthetics medication. However, its safety and underlying molecular mechanism of neurotoxicity largely remain unknown. Therefore, it is meaningful to investigate the safety of EIso and to further elucidate its mechanism of anesthetic neurotoxicity. Human neuroblastoma SHSY-5Y cells were cultured, followed by a random exposure to one of three doses of EIso (0.56mmol/l, 1.12mmol/l, and 2.24mmol/l) or the corresponding intralipid as vehicle (0.3956µl/ml, 0.7912µl/ml and 1.5824µl/ml) for 6h, 12h or 24h. Cell viability was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5- diphenyl tetrazolium bromide (MTT) assay and the morphological changes were determined by a light microscope. We detect JNK, p-JNK and cytochrome C (cyto C) protein levels by western blotting. SP600125, a specific inhibitor of JNK, was used to detect the role of JNK pathway in the neurotoxicity of EIso. Our study showed that EIso reduced the viability of SHSY-5Y cells in a dose- and time-dependent manner. 0.56mmol/l EIso has no significant effects on cell viability, while 1.12mmol/l of EIso with 24-h and 2.24mmol/l of EIso with over 12-h exposure notably reduced cell viability. EIso dramatically increased the levels of p-JNK and cyto C. The JNK pathway inhibitor SP600125 significantly increased the cell viability of SHSY-5Y cells induced by EIso. These findings suggest that EIso induces damage in human neuroblastoma SHSY-5Y cells by JNK signaling pathway activation and cyto C release. SP600125 protects neural cells against EIso-induced injury. Our findings provide a new insight in the exploration of potential novel therapeutic strategies for the treatment of EIso-induced neurotoxicity and other neurodegenerative diseases.

Fecal bacteria from treatment-naive Crohn's disease patients can skew helper T cell responses.

Many studies have demonstrated that the inflamed mucosa of Crohn's disease (CD) patients presented a disturbed gut commensal community, and the shift in microbial composition and species variety is associated with disease severity. To establish a link between changes in the intestinal bacterial composition and the alteration of inflammation, we obtained fecal bacteria from CD patients and non-CD controls. The bacteria were then used to stimulate the peripheral blood mononuclear cells (PBMCs) from one non-CD individual. We found that the frequency of IFN-γ- and IL-17-expressing CD4 T cells was significantly higher after stimulation with CD bacteria than with non-CD bacteria, while the frequency of IL-4- and IL-10-expressing CD4 T cells was significantly decreased after stimulation with CD bacteria. A similar trend was observed in the level of cytokine expression and transcription expression. However, this difference was not clear-cut, as overlapping regions were observed between the two groups. With longer stimulation using CD bacteria, the skewing toward Th1/Th17 responses were further increased. This increase depended on the presence of monocytes/macrophages. Interestingly, we also found that B cells presented an inhibitory effect in CD bacteria-mediated skewing toward Th1/Th17 cells and promoted IL-10 secretion in CD bacteria-stimulated PBMCs. Together, our results demonstrated that CD bacteria could promote Th1/Th17 inflammation in a host factor-independent fashion.