Methyl jasmonate regulation of pectin polysaccharides in Cosmos bipinnatus roots: A mechanistic insight into alleviating cadmium toxicity.

Methyl jasmonate (MeJA), a crucial phytohormone, which plays an important role in resistance to Cadmium (Cd) stress. The cell wall (CW) of root system is the main location of Cd and plays a key role in resistance to Cd toxicity. However, the mechanism effect of MeJA on the CW composition and Cd accumulation remain unclear. In this study, the contribution of MeJA in regulating CW structure, pectin composition and Cd accumulation was investigated in Cosmos bipinnatus. Phenotypic results affirm MeJA's significant role in reducing Cd-induced toxicity in C. bipinnatus. Notably, MeJA exerts a dual impact, reducing Cd uptake in roots while increasing Cd accumulation in the CW, particularly bound to pectin. The molecular structure of pectin, mainly uronic acid (UA), correlates positively with Cd content, consistent in HC1 and cellulose, emphasizing UA as pivotal for Cd binding. Furthermore, MeJA modulates pectin methylesterase (PME) activity under Cd stress, influencing pectin's molecular structure and homogalacturonan (HG) content affecting Cd-binding capacity. Chelate-soluble pectin (CSP) within soluble pectins accumulates a substantial Cd proportion, with MeJA regulating both UA content and the minor component 3-deoxy-oct-2-ulosonic acid (Kdo) in CSP. The study delves into the intricate regulation of pectin monosaccharide composition under Cd stress, revealing insights into the CW's physical defense and Cd binding. In summary, this research provides novel insights into MeJA-specific mechanisms alleviating Cd toxicity in C. bipinnatus, shedding light on complex interactions between MeJA, and Cd accumulation in CW pectin polysaccharide.

Post-endoscopic submucosal dissection phlegmonous enteritis: A case report and literature review.

Background: This study presents the initial case of phlegmonous enteritis following endoscopic submucosal dissection (ESD), a rare and potentially fatal complication. Additionally, a comprehensive review of relevant literature is provided. Case report: A 66-year-old female patient, diagnosed with Hashimoto's thyroiditis and thrombocytopenia, underwent ESD to address a laterally spreading tumor located in the ascending colon. After the procedure, the patient manifested abdominal pain and a high fever, was diagnosed with peritonitis, necessitating an emergency exploratory laparotomy and right hemicolectomy. Subsequent histological examination indicated a significant presence of neutrophil infiltration across all layers of the intestines. The ascites culture yielded the growth of Escherichia coli. Literature review: A search was conducted in the PubMed database to identify case reports conforming to the definition of phlegmonous enteritis proposed by Rokitansky et al. We retrieved about 30 studies regarding phlegmonous enteritis from 1951 to 2022, with around 39 cases. Among these, only 28 patients had comprehensive medical data available. Subsequently, an examination of the literature was undertaken to explore the pathogenesis, prevention, and treatment of phlegmonous enteritis. Conclusion: The possibility of phlegmonous enteritis should be taken into consideration in cases of unexplained acute abdomen, particularly in patients with compromised immunity, in order to provide active surgical and antibiotic interventions.

Morphological Structure and Physiological and Biochemical Responses to Drought Stress of Iris japonica.

Drought is among the most important abiotic stresses on plants, so research on the physiological regulation mechanisms of plants under drought stress can critically increase the economic and ecological value of plants in arid regions. In this study, the effects of drought stress on the growth status and biochemical indicators of Iris japonica were explored. Under drought stress, the root system, leaves, rhizomes, and terrestrial stems of plants were sequentially affected; the root system was sparse and slender; and the leaves lost their luster and gradually wilted. Among the physiological changes, the increase in the proline and soluble protein content of Iris japonica enhanced the cellular osmotic pressure and reduced the water loss. In anatomical structures, I. japonica chloroplasts were deformed after drought treatment, whereas the anatomical structures of roots did not substantially change. Plant antioxidant systems play an important role in maintaining cellular homeostasis; but, as drought stress intensified, the soluble sugar content of terrestrial stems was reduced by 55%, and the ascorbate peroxidase, glutathione reductase, and monodehydroascorbate reductase (MDHAR) activities of leaves and the MDHAR activity of roots were reduced by 29%, 40%, 22%, and 77%, respectively. Overall, I. japonica was resistant to 63 days of severe drought stress and resisted drought through various physiological responses. These findings provide a basis for the application of I. japonica in water-scarce areas.

Stem cell factor modulates HIF-1α levels and diminishes 5-FU sensitivity in 5-FU resistant pancreatic cells by altering the anabolic glucose metabolism.

Resistance to chemotherapy in cancer leads to poor therapeutic outcomes and also leads to challenges in treatment. The present work evaluated the mechanism involved in the resistance of 5-flurouracil (5-FU) in pancreatic cancer. At least 14 different pancreatic cancer (PC) cell lines were used for the study. For in vivo study female nude mice were selected. Patient-derived tumor xenograft samples were obtained from patients. The study involved, study for glucose uptake, fluorescence-activated cell sorting for glucose transporter, 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide for cell survival, Picto-micrography for clonogenic assay, glutamine uptake assay, extracellular acidification and oxygen consumption rate, carbon dioxide release assay and lactate assay were also done. In addition to this, quantitative real-time polymerase chain reaction analysis for expression of genes, chromatin immunoprecipitation assay, western blot for protein expression, and immunohistochemical analysis in tumor sections, the tumors were studied by imaging for hypoxia and localization of TKT and CTPS-2. Also, patient-derived xenograft tumors were engrafted in nude mice, followed by a glucose uptake assay. We reported that elevated glycolytic flux causes dependence on glucose in cancer cells and, at the same time, increases pyrimidine biosynthesis. It was also found that stem cell factor-mediated stabilization of hypoxia-inducible factor-1a (HIF-1α) modulates the resistance in PC. Targeting HIF-1α in combination with 5-FU, strongly reduced the tumor burden. The study concludes that stem cell factor modulates HIF-1α and decreases the sensitivity in 5-FU resistant pancreatic cancer cells by targeting glucose metabolism. Deceased expression levels of CTPS-2 and TKT, which are regulators of pyrimidine biosynthesis could better the chance of survival in patients of pancreatic cancer receiving treatment of 5-FU.

Critical role of caveolin-1 in intestinal ischemia reperfusion by inhibiting protein kinase C ßII.

Intestinal ischemia reperfusion (I/R) is a common clinical pathological process. We previously reported that pharmacological inhibition of protein kinase C (PKC) ßII with a specific inhibitor attenuated gut I/R injury. However, the endogenous regulatory mechanism of PKCßII inactivation is still unclear. Here, we explored the critical role of caveolin-1 (Cav1) in protecting against intestinal I/R injury by regulating PKCßII inactivation. PKCßII translocated to caveolae and bound with Cav1 after intestinal I/R. Cav1 was highly expressed in the intestine of mice with I/R and IEC-6 cells stimulated with hypoxia/reoxygenation (H/R). Cav1-knockout (KO) mice suffered from worse intestinal injury after I/R than wild-type (WT) mice and showed extremely low survival due to exacerbated systemic inflammatory response syndrome (SIRS) and remote organ (lung and liver) injury. Cav1 deficiency resulted in excessive PKCßII activation and increased oxidative stress and apoptosis after intestinal I/R. Full-length Cav1 scaffolding domain peptide (CSP) suppressed excessive PKCßII activation and protected the gut against oxidative stress and apoptosis due to I/R injury. In summary, Cav1 could regulate PKCßII endogenous inactivation to alleviate intestinal I/R injury. This finding may represent a novel therapeutic strategy for the prevention and treatment of intestinal I/R injury.

Autoamputation of the appendix and survival of the amputated part: a rare case report and literature review.

BACKGROUND: Autoamputation of the appendix, i.e., complete separation of a part of the appendix without any surgical intervention, has been rarely documented in the literature in recent years. Herein, we report a case where the amputated part of the appendix was viable after autoamputation and reviewed the related literature. CASE PRESENTATION: A 39-year-old female patient was admitted to our hospital complaining of abdominal pain and subsequently underwent an emergency laparoscopic appendectomy (LA). Intraoperatively, we found an abnormally short appendix protruding from the cecum and a strip-like tissue attached to the mesoappendix, considered a duplex appendix, was resected. Finally, in conjunction with the histopathology findings and the past medical history, the patient was diagnosed with "Pseudo-duplication of the Appendix". CONCLUSIONS: Autoamputation of the appendix resulting in preserved tissue viability and absence of necrosis at both ends, can be termed as "Pseudo-duplication of the Appendix". This condition is very rare in clinical practice and has not been reported in China, to the best of our knowledge. It has been established that the autoamputated appendix can produce chronic inflammation, intestinal fistulae and even cancer, affecting the patient's quality of life. Accordingly, a clear diagnosis and timely management are essential. In this report, we established a novel classification for "Pseudo-duplication of the Appendix", hoping that our report will help surgeons better understand this anatomical anomaly of the appendix, to help during the differential diagnosis process and avoid confusion.

Bioinformatics analysis reveals the clinical significance of GIPC2/GPD1L for colorectal cancer using TCGA database.

Background: Colorectal cancer (CRC) causes 700,000 deaths annually and is the fourth deadliest cancer in the world after lung, liver, and stomach cancer. Since CRC is difficult to detect early and has a poor prognosis, it is critical to develop novel biomarkers for its diagnosis, prognosis, and treatment. Methods: The GIPC2 expression in colorectal cancer was examined by the TCGA database analysis, IHC from the human protein atlas and qRT-PCR tests. GO and KEGG enrichment analyses were performed for genes that were both correlated with the expression of GIPC2 and GPD1L. The receiver operating characteristic curve (ROC) analysis and Kaplan-Meier (KM) survival analysis were applied to analyze the prognostic value of GIPC2 and GPD1L for overall survival (OS) and progress free interval (PFI) of CRC patients. Results: We found that GIPC2 was low expressed in colorectal cancer and highly related with the CRC clinical-stage grade and TNM stage. Furthermore, GPD1L is correlated with GIPC2 via the correlation analysis in CRC and they were associated with several important cancer-related pathways. GIPC2 and GPD1L exhibited good diagnostic and prognostic predictive ability for patients with CRC. Conclusions: These results revealed new biomarkers in CRC, we proposed that the GIPC2/GPDL1 might be potential diagnostic and prognostic indicators for CRC, which provides a theoretical basis for our subsequent cellular and animal experiments, so as to reveal the occurrence and development mechanism of CRC more comprehensively.

Systemic Immune-Inflammation Index (SII) Can Be an Early Indicator for Predicting the Severity of Acute Pancreatitis: A Retrospective Study.

OBJECTIVE: Systemic immune-inflammation index (SII) is a new systemic inflammatory prognostic indicator associated with outcomes in patients with different tumors. Studies have shown an association between SII and many chronic/acute inflammatory diseases. This study aimed at exploring whether SII can be used as an effective parameter for predicting the severity of acute pancreatitis (AP). METHODS: A total of 101 acute pancreatitis patients were enrolled in this study (mild acute pancreatitis (MAP): n = 73 and severe acute pancreatitis (SAP): n = 28). Patient demographics and SII were analyzed using the chi-square test, Student's t-test, and Mann-Whitney U-test. A receiver operating characteristic curve was generated to test the potential of using neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), and SII to predict AP's severity. Logistic regression analysis was performed to determine major risk factors. RESULTS: Patients with SII value ≥2207.53 had a higher probability of having SAP (sensitivity = 92.9%, specificity = 87.7%, and AUC = 0.920), and SII was a significantly better predictive value than PLR and NLR. Logistic regression analysis results showed SII could differentiate MAP from SAP as a major risk factor. CONCLUSION: This study has shown that SII is a potential indicator for predicting the severity of acute pancreatitis. The findings suggested that SII is more sensitive and specific than NLR and PLR in predicting the severity of acute pancreatitis.

Haemorrhagic retroperitoneal paraganglioma initially manifesting as acute abdomen: a rare case report and literature review.

BACKGROUND: Paragangliomas (PGLs) are extremely rare neuroendocrine tumours arising from extra-adrenal chromaffin cells. PGLs are clinically rare, difficult to diagnose and usually require surgical intervention. PGLs mostly present catecholamine-related symptoms. We report a case of Acute abdomen as the initial manifestation of haemorrhagic retroperitoneal PGL. There has been only one similar case reported in literature. CASE PRESENTATION: We present a unique case of a 52-year-old female with acute abdomen induced by haemorrhagic retroperitoneal PGL. The patient had a 5-h history of sudden onset of serve right lower quadrant abdominal pain radiating to the right flank and right lumbar region. Patient had classic symptoms of acute abdomen. Abdominal ultrasound revealed a large abdominal mass with a clear boundary. A Computed Tomography Angiography (CTA) of superior mesenteric artery was also performed to in the emergency department. The CTA demonstrated a large retroperitoneal mass measured 9.0 × 7.3 cm with higher density inside. A provisional diagnosis of retroperitoneal tumour with haemorrhage was made. The patient received intravenous fluids, broad-spectrum antibiotics and somatostatin. On the 3rd day of admission, her abdominal pain was slightly relieved, but haemoglobin decreased from 10.9 to 9.4 g/dL in 12 h suggesting that there might be active bleeding in the abdominal cavity. Thus, we performed a midline laparotomy for the patient. Haemorrhage was successfully stopped during operation. The retroperitoneal tumour with haemorrhage was completely removed. The abdominal pain was significantly relieved after surgery. The patient initially presented with acute abdomen instead of catecholamine-related symptoms. The diagnosis of retroperitoneal PGL with haemorrhage was finally confirmed by postoperative pathological and immunohistochemical results. The postoperative course was uneventful. At the 1-year follow-up visit, no tumour recurrence was observed by Single Photon Emission Computed Tomography. A literature review was performed to further understand and analyse the aforementioned disease. CONCLUSION: Acute abdomen as the initial manifestation of haemorrhagic retroperitoneal paraganglioma is extremely rare. Abdominal Computed Tomography is essential to locate the lesion and differentiate between other causes of acute abdomen. PGLs are hypervascular tumours. We should be aware that ruptured retroperitoneal PGL with massive bleeding could be life threatening and require emergency laparotomy.

GDC-0941 and CXCL8 (3-72) K11R/G31P combination therapy confers enhanced efficacy against breast cancer.

Aim: Herein is presented the combined effect of PI3K inhibitor (GDC-0941) and CXCR1/2 analogue (G31P) in breast cancer. Materials & methods: Breast cancer cell lines and xenograft model were employed to test the efficacy of the combination therapy. Results: GDC-0941+G31P treatment substantially inhibited multiplication of all the breast cancer cell lines used in this study (BT474, HCC1954 and 4T1). Even though single therapies caused a meaningful S-phase cell cycle arrest, the inhibition effect was more potent with the combined treatment. Similarly, enhanced apoptosis accompanied GDC-0941+G31P treatment. Furthermore, the migration ability of the breast cancer cell lines were significantly curtailed by the combination therapy compared with the single treatments. Conclusion: The findings suggest that combination treatment involving PI3K inhibitor and CXCR1/2 analogue (G31P) could be a potent therapeutic option for breast cancer treatment.

Author Correction: Macrophages confer resistance to PI3K inhibitor GDC-0941 in breast cancer through the activation of NF-κB signaling.

Since publication of this article, the authors have noticed the following errors: (1) Fig. 3c, the image is correct but the authors mistakenly provided incorrect figure legend. The correct figure legend is included below along with the original figure. (2) Supplementary Fig. S2, the authors mistakenly provided the data from ELISA analysis of TNFα and IL-6 in media from co-cultured 4T1 and RAW264.7 cells. As stated in the main text, data from ELISA analysis of TNFα and IL-6 in 4T1 tumors from Balb/c mice treated with GDC-0941 should be provided. The correct figure and figure legend are included below. (3) The authors noticed an error in the manuscript in which "RAW276.7" should be "RAW264.7". The corrections do not alter the conclusions of the paper. The authors apologize for any inconvenience caused. This has been corrected in both the PDF and HTML versions of the Article.

Pseudomyxoma peritonei induced by low-grade appendiceal mucinous neoplasm accompanied by rectal cancer: a case report and literature review.

BACKGROUND: Pseudomyxoma peritonei (PMP) is a disease involving the peritoneum characterized by the production of large quantities of mucinous ascites. PMP has a low incidence, is difficult to diagnose, and has a guarded prognosis. PMP induced by low-grade appendiceal mucinous neoplasm is extremely rare, and PMP accompanied by rectal cancer is even rarer. CASE PRESENTATION: We present a unique case of a 70-year-old male with PMP induced by low-grade appendiceal mucinous neoplasm accompanied by rectal cancer. The patient's clinical, surgical, and histologic data were reviewed. The patient had persistent distended abdominal pain without radiating lower back pain, abdominal distension for 1 month, and no exhaustion or defecation for 4 days. A transabdominal ultrasound-guided biopsy was performed on the first day. The patient received an emergency exploratory laparotomy because of increased abdominal pressure. We performed cytoreductive surgery, enterolysis, intestinal decompression, special tumour treatment and radical resection of rectal carcinoma. The postoperative course was uneventful. The postoperative histological diagnoses were PMP, low-grade appendiceal mucinous neoplasm and rectal medium differentiated adenocarcinoma. At the 1-year follow-up visit, no tumour recurrence was observed by computed tomography (CT). We also performed a literature review. CONCLUSIONS: We should be aware that PMP can rarely be accompanied by rectal cancer, which represents an easily missed diagnosis and increases the difficulty of diagnosis and treatment. Additionally, there are some typical characteristics of PMP with respect to diagnosis and treatment.

MYC status as a determinant of synergistic response to Olaparib and Palbociclib in ovarian cancer.

BACKGROUND: While PARP inhibitors and CDK4/6 inhibitors, the two classes of FDA-approved agents, have shown promising clinical benefits, there is an urgent need to develop new therapeutic strategies to improve clinical response. Meanwhile, extending the utility of these inhibitors beyond their respective molecularly defined cancer types is challenging and will likely require biomarkers predictive of treatment response especially when used in a combination drug development setting. METHODS: The effects of PARP inhibitor Olaparib and CDK4/6 inhibitor Palbociclib on ovarian cancer cells lines including those of high-grade serous histology were examined in vitro and in vivo. We investigated the molecular mechanism underlying the synergistic effects of drug combination. FINDINGS: We show for the first time that combining PARP and CDK4/6 inhibition has synergistic effects against MYC overexpressing ovarian cancer cells both in vitro and in vivo. Mechanistically, we find that Palbociclib induces homologous recombination (HR) deficiency through downregulation of MYC-regulated HR pathway genes, causing synthetic lethality with Olaparib. We further demonstrate that MYC expression determines sensitivity to combinatorial treatment with Olaparib and Palbociclib. INTERPRETATION: Our data provide a rationale for clinical evaluation of therapeutic synergy of these two classes of inhibitors in ovarian cancer patients whose tumors show high MYC expression and who do not respond to PARP inhibitors or CDK4/6 inhibitors monotherapies. FUND: This work was supported by the National Natural Science Foundation of China [81672575, 81874111, 81472447 to HC; 81572586 and 81372853 to PL], and the Liaoning Provincial Key Basic Research Program for Universities [LZ2017002 to HC].

Patient-derived xenograft mouse models: A high fidelity tool for individualized medicine.

Patient-derived xenograft (PDX) mouse models involve the direct transfer of fresh human tumor samples into immunodeficient mice following surgical resection or other medical operations. Gene expression in tumors may be maintained by serial passages of tumors from mouse to mouse. These models aid research into tumor biology and pharmacology without manual manipulation of cell cultures in vitro. and are widely used in individualized cancer therapy/translational medicine, drug development and coclinical trials. PDX models exhibit higher predictive values for clinical outcomes than cell line-derived xenograft models and genetically engineered mouse models. However, PDX models are associated with certain challenges in clinical application. The present study reviewed current collections of PDX models and assessed the challenges and future directions of this field.

Inhibition of BTF3 sensitizes luminal breast cancer cells to PI3Kα inhibition through the transcriptional regulation of ERα.

Selective phosphatidylinositol 3 kinase (PI3K) inhibitors are being actively tested in clinical trials for ERα-positive (ER+) breast cancer due to the presence of activating PIK3CA mutations. However, recent studies have revealed that increased ERα transcriptional activity limits the efficacy of PI3K inhibitor monotherapy for ER + breast cancers. Herein, we report the identification of BTF3 as an oncogenic transcription factor that regulates ERα expression in luminal breast cancers. Our TCGA analysis reveals high expression levels of BTF3 in luminal/ER + breast cancer and cell line models harboring ERα overexpression. Concordantly, BTF3 expression is highly and strongly associated with ESR1 expression in multiple breast cancer cohorts. We further show that BTF3 promotes the proliferation, survival and migration of ER + breast cancer cells by modulating ESR1 expression and ERα-dependent transcription. Moreover, BTF3 knockdown sensitizes ER + breast cancer cells to the PI3Kα inhibitor BYL-719 in both in vitro and in vivo models. Together, our findings highlight a novel role of BTF3 in modulation of ERα-dependent transcriptional activity and its potential as a predictive marker for the response to PI3K-targeted therapy in ER + breast cancer.

Macrophages confer resistance to PI3K inhibitor GDC-0941 in breast cancer through the activation of NF-κB signaling.

The PI3K pathway is one of the most dysregulated signaling pathways in epithelial cancers and has become an attractive therapeutic target under active preclinical and clinical development. However, recent clinical trial studies revealed that blockade of PI3K activity in advanced cancer often leads to the development of resistance and relapse of the diseases. Intense efforts have been made to elucidate resistance mechanisms and identify rational drug combinations with PI3K inhibitors in solid tumors. In the current study, we found that PI3K inhibition by GDC-0941 increased macrophage infiltration and induced the expression of macrophage-associated cytokines and chemokines in the mouse 4T1 breast tumor model. Using the in vitro co-culture system, we showed that the presence of macrophages led to the activation of NF-κB signaling in 4T1 tumor cells, rendering tumor cells resistant to PI3K inhibition by GDC-0941. Furthermore, we found that Aspirin could block the activation of NF-κB signaling induced by PI3K inhibition, and combined use of GDC-0941 and Aspirin resulted in attenuated cell growth and enhanced apoptosis of 4T1 cells in the in vitro co-culture system with the presence of macrophages. Consistently, the combination treatment also effectively reduced tumor burden, macrophage infiltration and pulmonary metastasis in in vivo 4T1 breast tumor model. Together, our results suggested macrophages in microenvironment may contribute to the resistance of breast cancer cells to PI3K inhibition and reveal a new combination paradigm to improve the efficacy of PI3K-targeted therapy.

Fish oil alleviates liver injury induced by intestinal ischemia/reperfusion via AMPK/SIRT-1/autophagy pathway.

AIM: To evaluate whether fish oil (FO) can protect liver injury induced by intestinal ischemia/reperfusion (I/R) via the AMPK/SIRT-1/autophagy pathway. METHODS: Ischemia in Wistar rats was induced by superior mesenteric artery occlusion for 60 min and reperfusion for 240 min. One milliliter per day of FO emulsion or normal saline was administered by intraperitoneal injection for 5 consecutive days to each animal. Animals were sacrificed at the end of reperfusion. Blood and tissue samples were collected for analyses. AMPK, SIRT-1, and Beclin-1 expression was determined in lipopolysaccharide (LPS)-stimulated HepG2 cells with or without FO emulsion treatment. RESULTS: Intestinal I/R induced significant liver morphological changes and increased serum alanine aminotransferase and aspartate aminotransferase levels. Expression of p-AMPK/AMPK, SIRT-1, and autophagy markers was decreased whereas tumor necrosis factor-α (TNF-α) and malonaldehyde (MDA) were increased. FO emulsion blocked the changes of the above indicators effectively. Besides, in LPS-stimulated HepG2 cells, small interfering RNA (siRNA) targeting AMPK impaired the FO induced increase of p-AMPK, SIRT-1, and Beclin-1 and decrease of TNF-α and MDA. SIRT-1 siRNA impaired the increase of SIRT-1 and Beclin-1 and the decrease of TNF-α and MDA. CONCLUSION: Our study indicates that FO may protect the liver against intestinal I/R induced injury through the AMPK/SIRT-1/autophagy pathway.

Reviewing the Management of Obstructive Left Colon Cancer: Assessing the Feasibility of the One-stage Resection and Anastomosis After Intraoperative Colonic Irrigation.

BACKGROUND: The management of obstructive left colon cancer (OLCC) remains debatable with the single-stage procedure of primary colonic anastomosis after cancer resection and on-table intracolonic lavage now being supported. PATIENTS AND METHODS: Patients with acute OLCC who were admitted between January 2008 and January 2015 were distributed into 5 different groups. Group ICI underwent emergency laparotomy for primary anastomosis following colonic resection and intraoperative colonic lavage; Group HP underwent emergency Hartmann's Procedure; Group CON consisted of patients treated by conservative management with subsequent elective open cancer resection; Group COL were colostomy patients; and Group INT consisted of patients who had interventional radiology followed by open elective colon cancer resection. The demographics of the patients and comorbidity, intraoperative data, and postoperative data were collected, with P < .05 as significant. RESULTS: There were 4 deaths in 138 cases (2.90%). There was only 1 patient who had anastomotic leakage (5.56%) in Group ICI, compared with none in Group HP and Group COL, 1 case in Group INT (7.69%), and 2 cases in Group CON (6.06%) (P > .05). Group INT and Group CON, when compared to the three surgical groups, Groups ICI, Group COL, and Group HP, individually, were statistically significant for the duration of surgery (P < .05). CONCLUSIONS: Primary anastomosis following colonic resection after irrigation can be safely performed in selected patients, with the necessary surgical expertise, with no increased risk in mortality, anastomotic leakage, and other postoperative complications.

Inhibition of p66Shc-mediated mitochondrial apoptosis via targeting prolyl-isomerase Pin1 attenuates intestinal ischemia/reperfusion injury in rats.

Intestinal epithelial oxidative stress and apoptosis constitute key pathogenic mechanisms underlying intestinal ischemia/reperfusion (I/R) injury. We previously reported that the adaptor 66 kDa isoform of the adaptor molecule ShcA (p66Shc)-mediated pro-apoptotic pathway was activated after intestinal I/R. However, the upstream regulators of the p66Shc pathway involved in intestinal I/R remain to be fully identified. Here, we focused on the role of a prolyl-isomerase, peptidyl-prolyl cis-trans isomerase (Pin1), in the regulation of p66Shc activity during intestinal I/R. Intestinal I/R was induced in rats by superior mesenteric artery (SMA) occlusion. Juglone (Pin1 inhibitor) or vehicle was injected intraperitoneally before I/R challenge. Caco-2 cells were exposed to hypoxia/reoxygenation (H/R) in vitro to simulate an in vivo I/R model. We found that p66Shc was significantly up-regulated in the I/R intestine and that this up-regulation resulted in the accumulation of intestinal mitochondrial reactive oxygen species (ROS) and massive epithelial apoptosis. Moreover, intestinal I/R resulted in elevated protein expression and enzyme activity of Pin1 as well as increased interaction between Pin1 and p66Shc. This Pin1 activation was responsible for the translocation of p66Shc to the mitochondria during intestinal I/R, as Pin1 suppression by juglone or siRNA markedly blunted p66Shc mitochondrial translocation and the subsequent ROS generation and cellular apoptosis. Additionally, Pin1 inhibition alleviated gut damage and secondary lung injury, leading to improvement of survival after I/R. Collectively, our findings demonstrate for the first time that Pin1 inhibition protects against intestinal I/R injury, which could be partially attributed to the p66Shc-mediated mitochondrial apoptosis pathway. This may represent a novel prophylactic target for intestinal I/R injury.