[The applications and challenges of combined monitoring of macro/micro-circulation and mitochondrial homeostasis in early warning of perioperative organ injury].

Perioperative organ injury is a leading risk factor for mortality in surgical patients. Given the current limitations in the timeliness and accuracy of markers for perioperative organ injury, this article proposes a comprehensive early-warning assessment system that jointly monitors the macro-circulation, micro-circulation, and mitochondrial homeostasis. Macro-circulation monitoring allows for real-time evaluation of key indicators such as blood pressure and cardiac output, while micro-circulation monitoring aids in assessing the status of microvascular perfusion. Monitoring of mitochondrial homeostasis provides timely insights into cellular energy metabolism. These three facets are interconnected and collectively determine the balance between tissue oxygenation and energy supply and demand. This article will elucidate commonly used monitoring methods and clinically valuable assessment models within this system, offering theoretical and technical guidance to deepen our understanding of the pathological processes of perioperative organ injury, enhance surgical safety and success rates, and improve patient prognosis and quality of life.

Correction to: Rat limbal niche cells can induce transdifferentiation of oral mucosal epithelial cells into corneal epithelial-like cells in vitro.

The original article [1] contains an error in Fig. 5e whereby the immunofluorescence of ΔNp63α in the ME group is incorrectly presented; thus, the corrected figure is shown ahead.

Prognostic role of tumor PIK3CA mutation in colorectal cancer: a systematic review and meta-analysis.

BACKGROUND: Somatic mutations in the phosphatidylinositol-4,5-bisphosphate 3-kinase/AKT pathway play a vital role in carcinogenesis. Approximately 15%-20% of colorectal cancers (CRCs) harbor activating mutations in PIK3CA, making it one of the most frequently mutated genes in CRC. We thus carried out a systematic review and meta-analysis investigating the prognostic significance of PIK3CA mutations in CRC. MATERIALS AND METHODS: Electronic databases were searched from inception through May 2015. We extracted the study characteristics and prognostic data of each eligible study. The hazard ratio (HR) and 95% confidence interval (CI) were derived and pooled using the random-effects Mantel-Haenszel model. RESULTS: Twenty-eight studies enrolling 12 747 patients were eligible for inclusion. Data on overall survival (OS) and progression-free survival (PFS) were available from 19 and 10 studies, respectively. Comparing PIK3CA-mutated CRC patients with PIK3CA-wild-type CRC patients, the summary HRs for OS and PFS were 0.96 (95% CI 0.83-1.12) and 1.20 (95% CI 0.98-1.46), respectively. The trim-and-fill, Copas model and subgroup analyses stratified by the study characteristics confirmed the robustness of the results. Five studies reported the CRC prognosis for PIK3CA mutations in exons 9 and 20 separately; neither exon 9 mutation nor exon 20 mutation in PIK3CA was significantly associated with patient survival. CONCLUSIONS: Our findings suggest that PIK3CA mutation has the neutral prognostic effects on CRC OS and PFS. Evidence was accumulating for the establishment of CRC survival between PIK3CA mutations and patient-specific clinical or molecular profiles.

Growth and acid production of Lactobacillus delbrueckii ssp. bulgaricus ATCC 11842 in the fermentation of algal carcass.

Algal carcass is a low-value byproduct of algae after its conversion to biodiesel. Dried algal carcass is rich in protein, carbohydrate, and multiple amino acids, and it is typically well suited for growth and acid production of lactic acid bacteria. In this study, Lactobacillus delbrueckii ssp. bulgaricus ATCC 11842 was used to ferment different algal carcass media (ACM), including 2% ACM, 2% ACM with 1.9% glucose (ACM-G), and 2% ACM with 1.9% glucose and 2g/L amino acid mixture (ACM-GA). Concentrations of organic acids (lactic acid and acetic acid), acetyl-CoA, and ATP were analyzed by HPLC, and activities of lactate dehydrogenase (LDH), acetokinase (ACK), pyruvate kinase (PK), and phosphofructokinase (PFK) were determined by using a chemical approach. The growth of L. bulgaricus cells in ACM-GA was close to that in the control medium (de Man, Rogosa, and Sharpe). Lactic acid and acetic acid contents were greatly reduced when L. bulgaricus cells were grown in ACM compared with the control medium. Acetyl-CoA content varied with organic acid content and was increased in cells grown in different ACM compared with the control medium. The ATP content of L. bulgaricus cells in ACM was reduced compared with that of cells grown in the control medium. Activities of PFK and ACK of L. bulgaricus cells grown in ACM were higher and those of PK and LDH were lower compared with the control. Thus, ACM rich in nutrients may serve as an excellent substrate for growth by lactic acid bacteria, and addition of appropriate amounts of glucose and amino acids can improve growth and acid production.

Implication of transcriptional repression in compound C-induced apoptosis in cancer cells.

Compound C, a well-known inhibitor of AMP-activated protein kinase (AMPK), has been reported to induce apoptosis in some types of cells. However, the underlying mechanisms remain largely unclear. Using a DNA microarray analysis, we found that the expression of many genes was downregulated upon treatment with compound C. Importantly, compound C caused transcriptional repression with the induction of p53, a well-known marker of transcriptional stress response, in several cancer cell lines. Compound C did not induce the phosphorylation of p53 but dramatically increased the protein level of p53 similar to some other transcriptional inhibitors, including 5,6-dichloro-1-ß-D-ribobenzimidazole (DRB). Consistent with previous reports, we found that compound C initiated apoptotic death of cancer cells in an AMPK-independent manner. Similar to DRB and actinomycin D (ActD), two classic transcription inhibitors, compound C not only resulted in the loss of Bcl-2 and Bcl-xl protein but also induced the phosphorylation of eukaryotic initiation factor-alpha (eIF2α) on Ser51. Hence, the phosphorylation of eIF2α might be a novel marker of transcriptional inhibition. It is noteworthy that compound C-mediated apoptosis of cancer cells is correlated with decreased expression of Bcl-2 and Bcl-xl and the phosphorylation of eIF2α on Ser51. Remarkably, compound C exhibits potent anticancer activities in vivo. Taken together, our data suggest that compound C may be an attractive candidate for anticancer drug development.

Unfolded protein response suppresses cisplatin-induced apoptosis via autophagy regulation in human hepatocellular carcinoma cells.

It has been shown that drug resistance is extremely common in hepatocellular carcinoma (HCC) and is one of the major problems in HCC chemotherapy. However, the detailed mechanisms remain largely unknown. We have previously shown that endoplasmic reticulum (ER) stress is involved in the tumorigenesis of HCC. Here, we demonstrated that the unfolded protein response (UPR) inhibits cisplatin-induced HCC cell apoptosis. In HCC cells, cisplatin treatment triggers the UPR, which subsequently inhibits cisplatin-induced apoptosis. Importantly, mild ER stress precondition suppresses the sensitivity of HCC cells to cisplatin-induced apoptosis through autophagy regulation. Furthermore, heat-shock protein 27 (Hsp27) is involved in the cytoprotective role of the UPR in cisplatin-induced apoptosis. We also demonstrated that Hsp27 inhibits cisplatin- induced HCC cell death through autophagy activation. Taken together, our results indicate that the UPR inhibits cisplatin-induced apoptosis in HCC cells, at least in part, by Hsp27-mediated autophagy activation.

In vivo measurement of the subchondral bone thickness of lumbar facet joint using magnetic resonance imaging.

OBJECTIVE: To measure in vivo thicknesses of the facet joint subchondral bone across genders, age groups, with or without low back pain symptom groups and spinal levels. METHODS: Lumbar (L1-L2 to L5-S1) magnetic resonance (MR) imaging was performed in 81 subjects (41 males and 40 females, mean age 37.6 years). Thicknesses of the subchondral bone were measured in 1620 facet joints using the MR images with custom-written image processing algorithms together with a multi-threshold segmentation technique using each facet joint's middle axial-slice. This method was validated with 12 cadaver facet joints, scanned with both MR and micro-computed tomography images. RESULTS: An overall average thickness value for the 1620 analyzed joints was measured as 1.56±0.01 mm. The subchondral bone thickness values showed significant increases with successive lower spinal levels in the subjects without low back pain. The facet joint subchondral bone thickness in asymptomatic females was much smaller than in asymptomatic males. Mean subchondral bone thickness in the superior facet was greater than that in the inferior facet in both female and male asymptomatic subjects. CONCLUSIONS: This study is the first to quantitatively show subchondral bone thickness using a validated MR-based technique. The subchondral bone thickness was greater in asymptomatic males and increased with each successive lower spinal level. These findings may suggest that the subchondral bone thickness increases with loading. Furthermore, the superior facet subchondral bone was thicker than the inferior facet in all cases regardless of gender, age or spinal level in the subjects without low back pain. More research is needed to link subchondral bone microstructure to facet joint kinematics and spinal loads.

PI3K/Akt promotes GRP78 accumulation and inhibits endoplasmic reticulum stress-induced apoptosis in HEK293 cells.

The potential pro-survival role of phosphatidylinositol 3-kinase (PI3K)/Akt during endoplasmic reticulum stress has been well-characterized. However, the detailed mechanisms remain largely unknown. Here, we showed that PI3K/Akt inhibition promoted endoplasmic reticulum stress-induced apoptosis in a glucose-regulated protein 78 (GRP78)-dependent manner. During endoplasmic reticulum stress, high levels of Akt phosphorylation were sustained for at least 18 h in HEK293 cells. Importantly, PI3K/Akt enhanced GRP78 accumulation through increasing its stability following endoplasmic reticulum stress. Furthermore, Akt1, but not Akt2 or Akt3, was involved in GRP78 stability regulation. These results suggest that PI3K/Akt inhibits endoplasmic reticulum stress-induced apoptosis in HEK293 cells, at least in part, by promoting GRP78 protein stability.

Synthesis, crystal structure and properties of a new dinuclear manganese(III) complex: a mimic for catalase.

A new dinuclear manganese (III) complex [(ac)Mn(bbml)(2)Mn(ac)] x (BF(4))(2) x 3.5H(2)O (Hbbml=[bis(2-benzimidazolylmethyl)amino]ethanol, Hac=acetic acid) was synthesized and characterized by several physical methods. X-ray structure analysis shows that the complex has a dimeric unit and the two Mn(III) atoms are bridged by the oxygen atoms of the two ligands, forming a bis (micro-alkoxo)dimanganese core. The Mn-Mn distance is 3.2103 A. Electrospray mass spectrometry (ES-MS) experiment shows that the complex cation may easily have lost one or two ac(-) and leave unoccupied coordination site which would favor the coordination and activation of hydrogen peroxide. Furthermore, its catalytic activity for the disproportionation of hydrogen peroxide and the effect of added heterocyclic base were also investigated. The complex has some similarities to manganese catalase in structure and activity.

Ezrin-radixin-moesin-binding phosphoprotein 50 is expressed at the apical membrane of rat liver epithelia.

Ezrin-radixin-moesin (ERM)-binding phosphoprotein 50 (EBP50) and NHE3 Kinase A regulatory protein (E3KARP) are membrane-cytoskeleton linking proteins that utilize 2 PSD-95/DIg/ZO-1 (PDZ) domains and an ERM binding site to coordinate cyclic adenosine monophosphate (cAMP)-regulated ion transport in a number of distinct epithelia. ERM family members serve to anchor EBP50 and E3KARP to the actin cytoskeleton and sequester protein kinase A (PKA) to these protein complexes. In hepatocytes and cholangiocytes, the epithelial cells of the bile secretory unit, cAMP-activated PKA stimulates secretion and bile formation, but the molecular mechanisms, including the potential contribution of EBP50 and E3KARP, remain undetermined. The present studies evaluated the comparative expression and localization of EBP50 and E3KARP in rat hepatocytes and cholangiocytes. Complementary DNAs encoding rat EBP50 and E3KARP were identified by reverse transcription-polymerase chain reaction in both epithelial cell types and subsequently sequenced. Northern and Western analysis showed the presence of EBP50 messenger RNA and protein in both hepatocytes and cholangiocytes. Confocal immunofluorescence revealed EBP50 was concentrated at the apical domain of both cell types. E3KARP was also expressed in cholangiocytes but had a distinct cytoplasmic/nuclear distribution. In dominant-negative transfection studies, patch clamp analysis of Mz-ChA1 cholangiocarcinoma cells showed that expression of the PDZ1 domain of EBP50 selectively decreased the endogenous cAMP-mediated Cl secretory response. The apical expression of EBP50, presence of specific ERM proteins, and functional effects of PDZ1 expression on cholangiocyte secretion suggest EBP50 is positioned to contribute to the organization and regulation of bile secretory proteins in both hepatocytes and cholangiocytes.

Terephthalaldehyde bis(thiosemicarbazone) bis(dimethylformamide) solvate.

The thiosemicarbazone molecule in C(10)H(12)N(6)S(2).2C(3)H(7)NO has -1 symmetry. The thiosemicarbazone moiety and the benzene ring are essentially coplanar, with mean and maximum deviations of 0.03 and 0. 11 A, respectively. The dimethylformamide molecules bridge the thiosemicarbazone moieties, forming two-dimensional sheets through N-H.O hydrogen bonds.