Search

We sought to evaluate whether combining body mass index (BMI) and fasting blood glucose (FBG) can refine the predictive value of new-onset prediabetes/diabetes after acute pancreatitis (NODAP).In this retrospective cohort study, we used Kaplan-Meier analysis to compare differences in the NODAP rate among 492 patients with different BMI or FBG levels, or with the combination of these 2 factors mentioned above.In all, 153 of 492 (31.1%) eligible patients finally developed NODAP. According to univariate and multivariate analyses, BMI (hazard ratio, 2.075; 95% confidence interval, 1.408-3.060; P0.001) and FBG (hazard ratio, 2.544; 95% confidence interval, 1.748-3.710; P0.001) were important predictors of the incidence of NODAP. Subsequently, we divided 492 eligible patients into 3 groups according to the median BMI and FBG values, and found that the NODAP rate in the high-risk group was significantly higher than that in the medium-risk group ( P = 0.018) or the low-risk group ( P0.001).Body mass index and FBG are independent predictors of NODAP. The combination of BMI and FBG can refine the prediction of NODAP and identify candidates for clinical prevention.

For each recollement of triangulated categories, there is an epivalence between the middle category and the comma category associated to a triangle functor from the category on the right to the category on the left. For a morphic enhancement of a triangulated category $\mathcal{T}$, there are three explicit ideals of the enhancing category, whose corresponding factor categories are all equivalent to the module category over $\mathcal{T}$. Examples related to inflation categories and weighted projective lines are discussed., Comment: all comments are welcome!

For a finite dimensional algebra $A$, we prove that the bounded homotopy category of projective $A$-modules and the bounded derived category of $A$-modules are dual to each other via certain categories of locally-finite cohomological functors. The duality gives rise to a $2$-categorical duality between certain strict $2$-categories involving the bounded homotopy categories and bounded derived categories, respectively. We apply the $2$-categorical duality to the study of triangle autoequivalence groups. These results are analogous to the ones in [M.R. Ballard, {\em Derived categories of sheaves on singular schemes with an application to reconstruction}, Adv. Math. {\bf 227} (2011), 895--919].

For a certain full additive subcategory X of an additive category A, one defines the lower extension groups in relative homological algebra. We show that these groups are isomorphic to the suspended Hom groups in the Verdier quotient category of the bounded homotopy category of A by that of X. Alternatively, these groups are isomorphic to the negative cohomological groups of the Hom complexes in the dg quotient category A/X, where both A and X are viewed as dg categories concentrated in degree zero., Comment: 10 pages

We call a triangulated category \emph{hereditary} provided that it is equivalent to the bounded derived category of a hereditary abelian category, where the equivalence is required to commute with the translation functors. If the triangulated category is algebraical, we may replace the equivalence by a triangle equivalence. We give two intrinsic characterizations of hereditary triangulated categories using a certain full subcategory and the non-existence of certain paths. We apply them to piecewise hereditary algebras.

We prove that any faithful Frobenius functor between abelian categories preserves the Gorenstein projective dimension of objects. Consequently, it preserves and reflects Gorenstein projective objects. We give conditions on when a Frobenius functor preserves the stable categories of Gorenstein projective objects, the singularity categories and the Gorenstein defect categories, respectively. In the appendix, we give a direct proof of the following known result: for an abelian category with enough projectives and injectives, its global Gorenstein projective dimension coincides with its global Gorenstein injective dimension., 15 pages; all comments are welcome!

We investigate the problem when the tensor functor by a bimodule yields a singular equivalence. It turns out that this problem is equivalent to the one when the Hom functor given by the same bimodule induces a triangle equivalence between the homotopy categories of acyclic complexes of injective modules. We give conditions on when a bimodule appears in a pair of bimodules, that defines a singular equivalence with level. We construct an explicit bimodule, which yields a singular equivalence between a quadratic monomial algebra and its associated algebra with radical square zero. Under certain conditions which include the Gorenstein cases, the bimodule does appear in a pair of bimodules defining a singular equivalence with level., Comment: 20 pages, all comments are welcome!

We introduce the notions of a $\mathbf{D}$-standard abelian category and a $\mathbf{K}$-standard additive category. We prove that for a finite dimensional algebra $A$, its module category is $\mathbf{D}$-standard if and only if any derived autoequivalence on $A$ is standard, that is, given by a two-sided tilting complex. We prove that if the subcategory of projective $A$-modules is $\mathbf{K}$-standard, then the module category is $\mathbf{D}$-standard. We provide new examples of $\mathbf{D}$-standard module categories., revised, comments are welcome

We exploit singular equivalences between artin algebras, that are induced from certain functors between the stable module categories. Such functors are called pre-triangle equivalences. We construct two pre-triangle equivalences connecting the stable module category over a quadratic monomial algebra and the one over an algebra with radical square zero. Consequently, we obtain an explicit singular equivalence between the two algebras.

Background: Aurora A kinase represent a feasible target in cancer therapy. Objective: To evaluate the proteomic response of human liver carcinoma cells to alisertib (ALS) and identify the molecular targets of ALS, we examined the effects of ALS on the proliferation, cell cycle, autophagy, apoptosis, and chemosensitivity in HepG2 cells. Method: The stable-isotope labeling by amino acids in cell culture (SILAC) based quantitative proteomic study was performed to evaluate the proteomic response to ALS. Cell cycle distribution and apoptosis were assessed using flow cytometry and autophagy was determined using flow cytometry and confocal microscopy. Results: Our SILAC proteomic study showed that ALS regulated the expression of 914 proteins, with 407 molecules being up-regulated and 507 molecules being down-regulated in HepG2 cells. Ingenuity pathway analysis (IPA) and KEGG pathway analysis identified 146 and 32 signaling pathways were regulated by ALS, respectively, which were associated with cell survival, programmed cell death, and nutrition-energy metabolism. Subsequently, the verification experiments showed that ALS remarkably arrested HepG2 cells in G2/M phase and led to an accumulation of aneuploidy via regulating the expression of key cell cycle regulators. ALS induced a marked autophagy in a concentration- and time-dependent manner via the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) signaling pathway. Autophagy inhibition promoted the pro-apoptotic effect of ALS, indicating a cyto-protective role of ALS-induced autophagy. ALS increased the chemosensitivity of HepG2 cells to cisplatin and doxorubicin. Conclusion: Taken together, ALS induces autophagy and cell cycle arrest in HepG2 cells via PI3K/Akt/mTOR-mediated pathway. Autophagy inhibition may promote the anticancer effect of ALS and sensitize the chemotherapy in HepG2 cells.

// Yan-Feng Huang 1 , Da-Jian Zhu 2 , Xiao-Wu Chen 3 , Qi-Kang Chen 2 , Zhen-Tao Luo 3 , Chang-Chun Liu 3 , Guo-Xin Wang 3 , Wei-Jie Zhang 3 and Nv-Zhu Liao 2 1 Department of Traditional Chinese Medicine, Shunde Hospital of Southern Medical University, Guangdong 528300, China 2 Department of Gastrointestinal Surgery, Shunde Women and Children’s Hospital Affiliated to Jinan University, Guangdong 528300, China 3 Department of Gastrointestinal Surgery, Shunde Hospital of Southern Medical University, Guangdong 528300, China Correspondence to: Da-Jian Zhu, email: zhudajian2016@126.com Keywords: curcumin, colorectal cancer, irinotecan, ROS, ER stress Received: May 13, 2016 Accepted: February 27, 2017 Published: April 04, 2017 ABSTRACT Although initially effective against metastatic colorectal cancer (CRC), irinotecan-based chemotherapy leads to resistance and adverse toxicity. Curcumin is well known for its anti-cancer effects in many cancers, including CRC. Here, we describe reactive oxygen species (ROS) generation and endoplasmic reticulum (ER) stress as important mechanisms by which curcumin enhances irinotecan’s effects on CRC cells. CRC cell lines were treated with curcumin and/or irinotecan for 24 h, and then evaluated using cell proliferation assays, cell apoptosis assays, cell cycle analysis, intracellular Ca 2+ measurements, ROS measurements and immunoblotting for key ER stress-related proteins. We found that cell viability was inhibited and apoptosis was increased, accompanied by ROS generation and ER stress activation in CRC cells treated with curcumin alone or in combination with irinotecan. Blocking ROS production attenuated the expression of two markers of ER stress: binding of immunoglobulin protein (BIP) and CCAAT/enhancer-binding protein homologous protein (CHOP). Blocking CHOP expression using RNA interference also inhibited ROS generation. These results demonstrated that curcumin could enhance the effects of irinotecan on CRC cells by inhibiting cell viability and inducing cell cycle arrest and apoptosis, and that these effects may be mediated, in part, by ROS generation and activation of the ER stress pathway.

Universal extensions arise naturally in the Auslander bijections. For an abelian category having Auslander-Reiten duality, we exploit a bijection triangle, which involves the Auslander bijections, universal extensions and the Auslander-Reiten duality. Some consequences are given, in particular, a conjecture by Ringel is verified.

We give two proofs to the following theorem and its generalization: if a finite dimensional algebra $A$ is derived equivalent to a smooth projective scheme, then any derived equivalence between $A$ and another algebra $B$ is standard, that is, isomorphic to the derived tensor functor by a two-sided tilting complex. The main ingredients of the proofs are as follows: (1) between the derived categories of two module categories, liftable functors coincide with standard functors; (2) any derived equivalence between a module category and an abelian category is uniquely factorized as the composition of a pseudo-identity and a liftable derived equivalence; (3) the derived category of coherent sheaves on a certain projective scheme is triangle-objective, that is, any triangle autoequivalence on it, which preserves the the isomorphism classes of complexes, is necessarily isomorphic to the identity functor.

To each symmetrizable Cartan matrix, we associate a finite free EI category. We prove that the corresponding category algebra is isomorphic to the algebra defined in [C. Geiss, B. Leclerc, and J. Schr\"{o}er, Quivers with relations for symmetrizable Cartan matrices I: Foundations, Invent. Math. 209 (2017), 61--158], which is associated to another symmetrizable Cartan matrix. In certain cases, the algebra isomorphism provides an algebraic enrichment of the well-known correspondence between symmetrizable Cartan matrices and graphs with automorphisms., Comment: 18 pages; a new version of arXiv: 1811.00294

We prove that any derived equivalence between triangular algebras is standard, that is, it is isomorphic to the derived tensor functor given by a two-sided tilting complex., Comments are welcome!

Human Aurora kinases, including Aurora kinase A (AURKA), B (AURKB), and C (AURKC), play an essential role in mitotic events such as monitoring of the mitotic checkpoint, creation of bipolar mitotic spindle and alignment of centrosomes on it, also regulating centrosome separation, bio-orientation of chromosomes and cytokinesis. AURKA and AURKB are key regulators of mitosis and centrosome via polymerizing microfilaments and controlling chromatid segregation. In particular, AURKA plays critical roles in the regulation of mitotic entry, centrosome function, bipolar spindle assembly, and chromosome segregation. AURKA has been found to be overexpressed in various solid and haematological cancers and has been linked with poor prognosis. Its important role in cancer initiation, growth, and metastasis has brought the focus to search for potent and selective AURKA inhibitors for cancer treatment. MLN8237, also known as alisertib, is one selective AURKA inhibitor that has shown remarkable anticancer effects in preclinical studies. Alisertib exhibits favourable pharmacokinetic properties. Alisertib has generally showed good partial response rates of 4-52% and good safety profiles in Phase I and II trials when it is solely administered as well as combined with cytotoxic chemotherapeutic drugs. Recently, the multicentre, randomized Phase III study of alisertib in patients with relapsed or refractory peripheral T-cell lymphoma has been discontinued due to unsatisfactory efficacy. The low risk of side effects, accessibility, and effectiveness of alisertib makes it a new promising anticancer therapy and further mechanistic and clinical studies are warranted.

For an additive category with a Serre duality and a finite group action, we compute explicitly the Serre duality on the category of equivariant objects. We prove that under certain conditions, the equivarianzation of an additive category with a periodic Serre duality still has a periodic Serre duality. A similar result is proved for fractionally Calabi-Yau triangulated categories.

Alogliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor that is a class of relatively new oral hypoglycaemic drugs used in patients with type 2 diabetes (T2DM), can be used as monotherapy or in combination with other anti-diabetic agents, including metformin, pioglitazone, sulfonylureas and insulin with a considerable therapeutic effect. Alogliptin exhibits favorable pharmacokinetic and pharmacodynamic profiles in humans. Alogliptin is mainly metabolized by cytochrome P450 (CYP2D6) and CYP3A4. Dose reduction is recommended for patients with moderate or worse renal impairment. Side effects of alogliptin include nasopharyngitis, upper-respiratory tract infections and headache. Hypoglycaemia is seen in about 1.5% of the T2DM patients. Rare but severe adverse reactions such as acute pancreatitis, serious hypersensitivity including anaphylaxis, angioedema and severe cutaneous reactions such as Stevens-Johnson syndrome have been reported from post-marketing monitoring. Pharmacokinetic interactions have not been observed between alogliptin and other drugs including glyburide, metformin, pioglitazone, insulin and warfarin. The present review aimed to update the clinical information on pharmacodynamics, pharmacokinetics, adverse effects and drug interactions, and to discuss the future directions of alogliptin.

With only 1.3-4.3% in total hepatic CYP content, human CYP2D6 can metabolize more than 160 drugs. It is a highly polymorphic enzyme and subject to marked inhibition by a number of drugs, causing a large interindividual variability in drug clearance and drug response and drug-drug interactions. The expression and activity of CYP2D6 are regulated by a number of physiological, pathological and environmental factors at transcriptional, post-transcriptional, translational and epigenetic levels. DNA hypermethylation and histone modifications can repress the expression of CYP2D6. Hepatocyte nuclear factor-4α binds to a directly repeated element in the promoter of CYP2D6 and thus regulates the expression of CYP2D6. Small heterodimer partner represses hepatocyte nuclear factor-4α-mediated transactivation of CYP2D6. GW4064, a farnesoid X receptor agonist, decreases hepatic CYP2D6 expression and activity while increasing small heterodimer partner expression and its recruitment to the CYP2D6 promoter. The genotypes are key determinants of interindividual variability in CYP2D6 expression and activity. Recent genome-wide association studies have identified a large number of genes that can regulate CYP2D6. Pregnancy induces CYP2D6 via unknown mechanisms. Renal or liver diseases, smoking and alcohol use have minor to moderate effects only on CYP2D6 activity. Unlike CYP1 and 3 and other CYP2 members, CYP2D6 is resistant to typical inducers such as rifampin, phenobarbital and dexamethasone. Post-translational modifications such as phosphorylation of CYP2D6 Ser135 have been observed, but the functional impact is unknown. Further functional and validation studies are needed to clarify the role of nuclear receptors, epigenetic factors and other factors in the regulation of CYP2D6.

Let A be an abelian category and B be the Happel-Reiten-Smalo tilt of A with respect to a torsion pair. We give necessary and sufficient conditions for the existence of a derived equivalence between A and B , which is compatible with the inclusion of B into the derived category of A . As applications, we obtain new derived equivalences related to splitting torsion pairs, TTF-triples and two-term silting subcategories, respectively. We prove that for the realization functor of any bounded t-structure, its denseness implies its fully-faithfulness.

Resistance to conventional chemotherapeutic agents, including irinotecan (CPT‑11), 5-fluorouracil and capecitabine is a major cause for therapeutic failure in patients with colorectal cancer (CRC). Increasing evidence has demonstrated that cancer cells exhibiting stem cell-like characteristics are associated with the development of resistance to chemotherapeutic agents. As a plant polyphenol, curcumin has been demonstrated to have the ability to ameliorate resistance of CRC to chemotherapeutic agents, but the associations among curcumin, cancer stem cells (CSCs) and chemoresistance of CRC remain unclear. The present study established a CPT‑11-resistant colon cancer cell line, LoVo/CPT‑11 cells, and detected the expression levels of CSC identification markers [cluster of differentiation (CD)44, CD133, epithelial cell adhesion molecule (EpCAM) and CD24] in parental cells and CPT‑11-resistant cells. It was revealed that the expression levels of the colon CSC markers in LoVo/CPT‑11 cells were significantly higher compared those in parental cells at the mRNA and protein level. The effect of curcumin on the chemoresistance to CPT‑11 and the expression levels of CSC identification markers in LoVo/CPT‑11 cells separately treated with curcumin and CPT‑11 were further investigated. The results revealed that curcumin significantly attenuated chemoresistance to CPT‑11, and treatment with curcumin resulted in a significant reduction of the expression levels of CSC identification markers. Furthermore, a tumor sphere formation assay was used to enrich colon CSCs from LoVo/CPT‑11 cells, and demonstrated that curcumin efficiently diminished the traits of colon CSCs, as evidenced by the inability to form tumor spheres, the reduction in the expression of CSC identification markers, and apoptosis-induced effects on sphere-forming cells treated with curcumin alone or in combination with CPT‑11. Altogether, the present data demonstrated that curcumin attenuated resistance to chemotherapeutic drugs through induction of apoptosis of CSCs among colon cancer cells. These findings may provide novel evidence for the therapeutic application of curcumin in CRC intervention.

Let $R$ be a two-sided Noetherian ring, and let $M$ be a nilpotent $R$-bimodule, which is finitely generated on both sides. We study Gorenstein homological properties of the tensor ring $T_{R}(M)$. Under certain conditions, the ring $R$ is Gorenstein if and only if so is $T_{R}(M)$. We characterize Gorenstein projective $T_{R}(M)$-modules in terms of $R$-modules.

Dipeptidyl peptidase-4 (DPP-4) inhibitors are a class of oral antidiabetic drugs that improve glycaemic control without causing weight gain or increasing hypoglycaemic risk in patients with type 2 diabetes mellitus (T2DM). The eight available DPP-4 inhibitors, including alogliptin, anagliptin, gemigliptin, linagliptin, saxagliptin, sitagliptin, teneligliptin, and vildagliptin, are small molecules used orally with identical mechanism of action and similar safety profiles in patients with T2DM. DPP-4 inhibitors may be used as monotherapy or in double or triple combination with other oral glucose-lowering agents such as metformin, thiazolidinediones, or sulfonylureas. Although DPP-4 inhibitors have the same mode of action, they differ by some important pharmacokinetic and pharmacodynamic properties that may be clinically relevant in some patients. The main differences between the eight gliptins include: potency, target selectivity, oral bioavailability, elimination half-life, binding to plasma proteins, metabolic pathways, formation of active metabolite(s), main excretion routes, dosage adjustment for renal and liver insufficiency, and potential drug-drug interactions. The off-target inhibition of selective DPP-4 inhibitors is responsible for multiorgan toxicities such as immune dysfunction, impaired healing, and skin reactions. As a drug class, the DPP-4 inhibitors have become accepted in clinical practice due to their excellent tolerability profile, with a low risk of hypoglycaemia, a neutral effect on body weight, and once-daily dosing. It is unknown if DPP-4 inhibitors can prevent disease progression. More clinical studies are needed to validate the optimal regimens of DPP-4 inhibitors for the management of T2DM when their potential toxicities are closely monitored.

The Na(+) /K(+) -translocating adenosine triphosphatase (ATPase) transports sodium and potassium across the plasma membrane and represents a potential target in cancer chemotherapy. Na(+) /K(+) -ATPase belongs to the P-type ATPase family (also known as E1-E2 ATPase), which is involved in transporting certain ions, metals, and lipids across the plasma membrane of mammalian cells. In humans, the Na(+) /K(+) -ATPase is a binary complex of an α-subunit that has four isoforms (α1 -α4 ) and a β-subunit that has three isoforms (β1 -β3 ). This review aims to update our knowledge on the role of Na(+) /K(+) -ATPase in cancer development and metastasis, as well as on how Na(+) /K(+) -ATPase inhibitors kill tumour cells. The Na(+) /K(+) -ATPase has been found to be associated with cancer initiation, growth, development, and metastasis. Cardiac glycosides have exhibited anticancer effects in cell-based and mouse studies via inhibition of the Na(+) /K(+) -ATPase and other mechanisms. Na(+) /K(+) -ATPase inhibitors may kill cancer cells via induction of apoptosis and autophagy, radical oxygen species production, and cell cycle arrest. They also modulate multiple signalling pathways that regulate cancer cell survival and death, which contributes to their antiproliferative activities in cancer cells. The clinical evidence supporting the use of Na(+) /K(+) -ATPase inhibitors as anticancer drugs is weak. Several phase I and phase II clinical trials with digoxin, Anvirzel, and huachansu (an intravenous formulated extract of the venom of the wild toad), either alone or more often in combination with other anticancer agents, have shown acceptable safety profiles but limited efficacy in cancer patients. Well-designed randomized clinical trials with reasonable sample sizes are certainly warranted to confirm the efficacy and safety of cardiac glycosides for the treatment of cancer.

We prove that a Hom-finite additive category having determined morphisms on both sides is a dualizing variety. This complements a result by Krause. We prove that in a Hom-finite abelian category having Serre duality, a morphism is right determined by some object if and only if it is an epimorphism. We give a characterization to abelian categories having Serre duality via determined morphisms.

We report a 51-year-old female patient with a solitary lymphangioma located in the upper splenic pole which was managed successfully with laparoscopic partial splenectomy. Surgery lasted 170 min and did not require blood transfusions. The patient recovered well post-operatively and was asymptomatic at the 3-mo follow-up. She had a normal platelet count and no recurrence on ultrasonography or computed tomography. Laparoscopic partial splenectomy is a safe, minimally invasive technique for the treatment of solitary splenic lymphangiomas in the splenic pole. We performed the procedure using the Habib(TM) 4X device. This laparoscopic bipolar radiofrequency device ensured a "bloodless" splenic parenchymal resection.

For an adjoint pair \((F, U)\) of functors, we prove that \(U\) is a separable functor if and only if the defined monad is separable and the associated comparison functor is an equivalence up to retracts. In this case, under an idempotent completeness condition, the adjoint pair \((F, U)\) is monadic. This applies to the comparison between the derived category of the category of equivariant objects in an abelian category and the category of equivariant objects in the derived category of the abelian category.

For a finite abelian group action on a linear category, we study the dual action given by the character group acting on the category of equivariant objects. We prove that the groups of equivariant autoequivalences on these two categories are isomorphic. In the triangulated situation, this isomorphism implies that the classifications of stable tilting objects for these two categories are in a natural bijection. We apply these results to stable tilting complexes on weighted projective lines of tubular type., comments welcome

We prove that any derived equivalence between derived-discrete algebras of finite global dimension is standard, that is, isomorphic to the derived tensor functor by a two-sided tilting complex., Comment: 19 pages

We prove that a certain homological epimorphism between two algebras induces a triangle equivalence between their singularity categories. Applying the result to a construction of matrix algebras, we describe the singularity categories of some non-Gorenstein algebras.

For a finite quiver without sources or sinks, we prove that the homotopy category of acyclic complexes of injective modules over the corresponding finite-dimensional algebra with radical square zero is triangle equivalent to the derived category of the Leavitt path algebra viewed as a differential graded algebra with trivial differential, which is further triangle equivalent to the stable category of Gorenstein projective modules over the trivial extension algebra of a von Neumann regular algebra by an invertible bimodule. A related, but different, result for the homotopy category of acyclic complexes of projective modules is given. Restricting these equivalences to compact objects, we obtain various descriptions of the singularity category of a finite-dimensional algebra with radical square zero, which contain previous results.

Crash Reduction Factor (CRF) is an important indicator for Economy Analysis of Safeguard Technology. This paper introduces the concept of CRF, and pointed out the limitations of its application. Meanwhile, it is necessary to adopt a variety of safeguard measures for multiple accident potential on a secton of highway in domestic mountainous rural road. Therefore, this paper presents the concept of general CRF. Then, multiple-event probability formula is proposed to calculate the generalized CRF for the feature of CRF. Finally. At last, discussed the work we needed to do if CRF was to be introduced into China.

Inherent and acquired chemoresistance reduce the effectiveness of irinotecan in the treatment of metastatic colorectal cancer (CRC). However, the molecular mechanisms underlying this resistance process are still unclear. Twist1 is one of the master transcription factors of epithelial-mesenchymal transition (EMT). Our previous study indicated that Twist1 is overexpressed in colon cancer tissues, and demonstrated that Twist1 plays a crucial role in the chemoresistance of CRC. In the present study, we further investigated how Twist1 contribute to acquired resistance to irinotecan in colon cancer. The irinotecan-resistant cells were established by gradual adaptation of increasing irinotecan concentrations in LoVo cells, named LoVo/CPT-11R cells. Results showed that cell viabilities to different anticancer drugs were markedly increased in LoVo/CPT-11R cells compared to LoVo cells. Moreover, LoVo/CPT-11R cells displayed EMT, CSC-like cellular morphology and relative biomarkers were also significantly increased. In addition, overexpressed Twist1 LoVo cells were established by lentivirus transfection assay, named LoVo/Twist1 cells. Results showed that the LoVo/Twist1 cells perform a distinctly decreased sensitivity to irinotecan, downregulated expression of E-cadherin, upregulated expression of cluster of differentiation 44 (CD44), and a significant enhancement of invasion and migration potential by regulation of MMP2 compared with control cells. In contrast, the inhibition of Twist1 transfected with siRNA could enhance the irinotecan sensitivity in LoVo/CPT-11R cells and downregulate the expression of vimentin and CD44. Our data provide evidence that EMT and CSC-like phenotype induced by Twist1 contribute to acquire resistance to irinotecan and enhanced migration and invasion in colon cancer.

There are no sensitive and specific biomarkers that aid in the clinical diagnosis and prognosis of hepatocellular carcinoma (HCC). The aim of the present study was to determine the mRNA and protein expression levels of beclin 1 (BECN1) and nuclear factor-κB (NF-κB)p65 in patients with HCC, to evaluate their value as potential diagnostic and prognostic biomarkers. Immunohistochemistry and in situ hybridization were used to detect the expression of hepatic BECN1 and NF-kBp65 in patients with HCC, hepatitis B virus (HBV) or cirrhosis, as compared with the expression levels in healthy subjects. The expression level of the BECN1 protein in the HCC tissue was significantly high compared with that in the cirrhotic, hepatitis and normal tissues. The expression of the BECN1 protein in the hepatitis tissue was significantly high compared with that of the cirrhotic and normal tissues. The expression of the BECN1 mRNA in the cancer tissue was significantly high compared with that of the cirrhotic and normal tissues, and the expression of the BECN1 mRNA in the hepatitis tissue was significantly higher than that of the cirrhotic and normal tissues. The expression of the NF-κBp65 protein in the cancer tissue was significantly high compared with that of the cirrhotic, hepatitis and normal tissues. The expression of the NF-κBp65 mRNA in-the cancer tissue was significantly high compared with that of the cirrhotic, hepatitis and normal tissues. BECN1 expression was positively correlated with NF-κBp65 expression in HCC. The abnormal expression of BECN1 and NF-κBp65 was closely associated with the development of HCC. Finally, a search in GeneGo pathway database observed a link between BECN1 and NF-κBp65 through multiple proteins. These results indicate that BECN1 and NF-κBp65 are upregulated in HCC, and that they may serve as useful biomarkers for HCC.

We introduce the notion of totally reflexive extension of rings. It unifies Gorenstein orders and Frobenius extensions. We prove that for a totally reflexive extension, a module over the extension ring is totally reflexive if and only if its underlying module over the base ring is totally reflexive.

We associate to a localizable module a left retraction of algebras; it is a homological ring epimorphism that preserves singularity categories. We study the behavior of left retractions with respect to Gorenstein homological properties (for example, being Gorenstein algebras or CM-free algebras). We apply the results to Nakayama algebras. It turns out that for a connected Nakayama algebra A, there exists a connected self-injective Nakayama algebra A′ such that there is a sequence of left retractions linking A to A′; in particular, the singularity category of A is triangle equivalent to the stable category of A′. We classify connected Nakayama algebras with at most three simple modules according to Gorenstein homological properties.

Piwi-interacting RNA (piRNA) plays an important role in the gonadal development and maintenance of Teleostei. In this study, piRNA libraries derived from the adult gonads of Japanese flounder (Paralichthys olivaceus) were generated using next-generation sequencing technology. Using zebrafish piRNAs as a reference, 5 865 unique candidate piRNAs were identified; 289 candidate piRNA clusters (PRCs) were generated from the above piRNAs. Among the isolated candidate PRCs, a total of 38 ovary-specific, 45 ovary-bias, 24 testis-specific, and 131 testis-bias PRCs were found. The relative expression levels of seven PRCs were validated through quantitative reverse transcription-polymerase chain reaction. The results of this study will help facilitate exploration of the development and maintenance of the phenotypic sex mechanism in P. olivaceus.

// Da-Jian Zhu 1, 2, * , Yan-Feng Huang 3, * , Xiao-Wu Chen 1 , Zhen-Tao Luo 1 , Guo-Xin Wang 1 , Chang-Chun Liu 1 , Wei-Jie Zhang 1 , Man-Zhao Ouyang 1 1 Department of Gastrointestinal Surgery, Shunde First People’s Hospital Affiliated to Southern Medical University, Guangdong 528300, China 2 Department of Gastrointestinal Surgery, Shunde Women and Children’s Hospital Affiliated to Jinan University, Guangdong 528300, China 3 Department of Traditional Chinese Medicine, Shunde First People’s Hospital Affiliated to Southern Medical University, Guangdong 528300, China * These authors have contributed equally to this work Correspondence to: Xiao-Wu Chen, email: drchenxiaowu@163.com Keywords: curcumin, colorectal cancer, irinotecan, diarrhea, oxidative stress Received: December 07, 2015 Accepted: May 12, 2016 Published: July 14, 2016 ABSTRACT OBJECTIVE: Development of treatment resistance and adverse toxicity limits the gains made by irinotecan in patients with colorectal cancer. According to our previous studies, we found that curcumin could enhance the efficacy of irinotecan-induced apoptosis of colorectal tumor cells in vitro. This study aims to examine the effectiveness of a combination treatment regimen of irinotecan and curcumin in the colorectal cancer xenograft model. RESULTS: Curcumin or irinotecan alone reduced the tumor volume, and the combination had the strongest anticancer effects. Oxidative stress was induced in tumor (MDA: P < 0.01, GPx: P < 0.05, PRDX4: P < 0.01), while was reduced in intestinal tissue (MDA: P < 0.01, SOD: P < 0.05, GPx: P < 0.01). The apoptosis in tumor was accompanied by up-regulation of apoptotic proteins (caspase-3: P < 0.01, Bax: P < 0.01), but down-regulation of anti-apoptotic proteins (pro-caspase-3: P < 0.01, Bcl-2: P < 0.01). Besides, the combination treatment alleviated diarrhea and intestine injury, and also restored the autophagy (PGC-1α: P < 0.05, Atg-7: P < 0.05, and LC3B: P < 0.05) and mitochondrial dynamics (Mfn-1: P < 0.01, Mfn-2: P < 0.01, Drp-1: P < 0.01, Fis-1: P < 0.05) in intestinal tissue. MATERIALS AND METHODS: Nude mice were implanted with LoVo colorectal cancer cells before randomization into the following treatment groups: control; curcumin only; irinotecan only; curcumin + irinotecan. After a 9-day treatment, we compared the tumor weight, tumor volume, morphological change of intestine, and oxidative stress factors (LDH, MDA, SOD, GPx). In addition, we detected the oxidative stress (PRDX4, MnSOD, and p53), apoptosis (Bax, Bcl-2, pro-caspase-3, cleaved-caspase-3) and autophagy (PGC-1α, Atg-7, and LC3B) signaling. CONCLUSIONS: Curcumin could enhance the efficacy of irinotecan-induced apoptosis of colorectal cancer in vivo, while restore the irinotecan-induced autophagy of small intestinal epithelium.

Berberine is one of the main alkaloids found in the Chinese herb Huang lian (Rhizoma Coptidis), which has been reported to have multiple pharmacological activities. This study aimed to analyze the molecular targets of berberine based on literature data followed by a pathway analysis using the PANTHER program. PANTHER analysis of berberine targets showed that the most classes of molecular functions include receptor binding, kinase activity, protein binding, transcription activity, DNA binding, and kinase regulator activity. Based on the biological process classification ofin vitroberberine targets, those targets related to signal transduction, intracellular signalling cascade, cell surface receptor-linked signal transduction, cell motion, cell cycle control, immunity system process, and protein metabolic process are most frequently involved. In addition, berberine was found to interact with a mixture of biological pathways, such as Alzheimer’s disease-presenilin and -secretase pathways, angiogenesis, apoptosis signalling pathway, FAS signalling pathway, Hungtington disease, inflammation mediated by chemokine and cytokine signalling pathways, interleukin signalling pathway, and p53 pathways. We also explored the possible mechanism of action for the anti-diabetic effect of berberine. Further studies are warranted to elucidate the mechanisms of action of berberine using systems biology approach.

We have previously examined the binding patterns of various substrates to human cytochrome P450 2D6 (CYP2D6) using a series of molecular modeling methods. In this study, we further explored the binding modes of various types of inhibitors to CYP2D6 using a combination of ligand- and protein-based modeling approaches. Firstly, we developed and validated a pharmacophore model for CYP2D6 inhibitors, which consisted of two hydrophobic features and one hydrogen bond acceptor feature. Secondly, we constructed and validated a quantitative structure-activity relationship (QSAR) model for CYP2D6 inhibitors which gave a poor to moderate prediction accuracy. Thirdly, a panel of CYP2D6 inhibitors were subject to molecular docking into the active site of wild-type and mutated CYP2D6 enzyme. We demonstrated that 8 residues in the active site (Leu213, Glu216, Ser217, Gln244, Asp301, Ser304, Ala305, and Phe483) played an important role in the binding to the inhibitors via hydrogen bond formation and/or π-π stacking interaction. Apparent changes in the binding modes of the inhibitors have been observed with Phe120Ile, Glu216Asp, Asp301Glu mutations in CYP2D6. Finally, we screened for potential binders/inhibitors from the Chinese herbal medicine Scutellaria baicalensis (Huangqin, Baikal Skullcap) using the established pharmacophore model for CYP2D6 inhibitors and molecular docking approach. Overall, 18 out of 40 compounds from S. baicalensis were mapped to the pharmacophore model of CYP2D6 inhibitors and most herbal compounds from S. baicalensis could be docked into the active site of CYP2D6. Our study has provided insights into the molecular mechanisms of interaction of synthetic and herbal compounds with human CYP2D6 and further benchmarking studies are needed to validate our modeling and virtual screening results.

Summary Background Osthole (Ost), a natural coumarin derivative, has been shown to inhibit many pro-inflammatory mediators and block voltage-gated Na+ channels. During inflammation, acidosis is an important pain inducer which activates nociceptors by gating depolarizing cationic channels, such as acid-sensing ion channel 3 (ASIC3). The aim of this study was to examine the effects of Ost on nucleus pulposus-evoked nociceptive responses and ASIC3 over-expression in the rat dorsal root ganglion, and to investigate the possible mechanism. Material/Methods Radicular pain was generated with application of nucleus pulposus (NP) to nerve root. Mechanical allodynia was evaluated using von Frey filaments with logarithmically incremental rigidity to calculate the 50% probability thresholds for mechanical paw withdrawal. ASIC3 protein expression in dorsal root ganglions (DRGs) was assessed with Western blot and immunohistochemistry. Membrane potential (MP) shift of DRG neurons induced by ASIC3-sensitive acid (pH6.5) was determined by DiBAC4 (3) fluorescence intensity (F.I.). Results The NP-evoked mechanical hyperalgesia model showed allodynia for 3 weeks, and ASIC3 expression was up-regulated in DRG neurons, reaching peak on Day 7. Epidural administration of Ost induced a remarkable and prolonged antinociceptive effect, accompanied by an inhibition of over-expressed ASIC3 protein and of abnormal shift of MP. Amiloride (Ami), an antagonist of ASIC3, strengthened the antinociceptive effect of Ost. Conclusions Up-regulation of ASIC3 expression may be associated with NP-evoked mechanical hyperalgesia. A single epidural injection of Ost decreased ASIC3 expression in DGR neurons and the pain in the NP-evoked mechanical hyperalgesia model. Osthole may be of great benefit for preventing chronic pain status often seen in lumbar disc herniation (LDH).

Sperm storage in vivo extends the time window for fertilisation in several animal species, from a few days to several years. The underlying storage mechanisms, however, are largely unknown. In this study, spermatozoa from the epididymis and oviduct of Chinese soft-shelled turtles were investigated to identify potentially relevant morphological features and transformations at different stages of sperm storage. Large cytoplasmic droplets (CDs) containing lipid droplets (LDs) were attached to the midpiece of most spermatozoa in the epididymis, without migrating down the sperm tail. However, they were absent from the oviductal spermatozoa, suggesting that CDs with LDs may be a source of endogenous energy for epididymal spermatozoa. The onion-like mitochondria recovered their double-membrane morphology, with typical cristae, within the oviduct at a later stage of storage, thus implying that mitochondrial metabolism undergoes alterations during storage. Furthermore, a well developed fibrous sheath on the long principal piece was the integrating ultrastructure for glycolytic enzymes and substrates. These novel morphological characteristics may allow turtle spermatozoa to use diverse energy metabolism pathways at different stages of storage.

Whether perioperative allogenic blood transfusion (ABT) has adverse effect on patients with gastric carcinoma (GC) surgery or not, that is controversial. Our study evaluated the association between ABT and some clinical outcomes of GC surgery patients. Data of relevant studies were based on PubMed, EMBASE, and the Cochrane Library search. The relative risk (RR) of 5-year survival rates, tumor recurrence, and postoperative complications were performed; subgroup analyses included district, transfusion rates, age, participants, sex, and tumor stage. The study was approved by the ethics committee of the First People's Hospital of Shunde. In total, 9189 participants from 16 studies were included in the meta-analysis. The 5-year survival rate was decreased for the GC patients with ABT (RR = 0.74, 95% confidence interval [CI] = 0.69–0.79), the risk of tumor recurrence was significantly higher for ABT patients (RR = 1.82, 95% CI = 1.32–2.51), and postoperative complications increased in ABT patients (RR = 1.36, 95% CI = 1.02–1.81), respectively; in subgroup analyses, 5-year survival rates were not associated with the transfusion rates (χ2 = 0.37, P = 0.54). Transfusion for patients undergoing GC surgery, even low transfusion rates, would reduce the 5-year survival rates, and elevated the risk of tumor recurrence and postoperative complication.