Deficiency in SLC25A15, a hypoxia-responsive gene, promotes hepatocellular carcinoma by reprogramming glutamine metabolism.

BACKGROUND & AIMS: The role of solute carrier family 25 member 15 (SLC25A15), a critical component of the urea cycle, in hepatocellular carcinoma (HCC) progression remains poorly understood. This study investigated the impact of SLC25A15 on HCC progression and its mechanisms. METHODS: We systematically investigated the function of SLC25A15 in HCC progression using large-scale data mining and cell, animal, and organoid models. Furthermore, we analyzed its involvement in reprogramming glutamine metabolism. RESULTS: SLC25A15 expression was significantly decreased in HCC tissues, and patients with low SLC25A15 levels had a poorer prognosis. Hypoxia-exposed HCC cells or tissues had lower SLC25A15 expression. A positive correlation between HNF4A, a transcription factor suppressed by hypoxia, and SLC25A15 was observed in both HCC tissues and cells. Modulating HNF4A levels altered SLC25A15 mRNA levels. SLC25A15 upregulated SLC1A5, increasing glutamine uptake. The reactive metabolic pathway of glutamine was increased in SLC25A15-deficient HCC cells, providing energy for HCC progression through additional lipid synthesis. Ammonia accumulation due to low SLC25A15 levels suppressed the expression of OGDHL (oxoglutarate dehydrogenase L), a switch gene that mediates SLC25A15 deficiency-induced reprogramming of glutamine metabolism. SLC25A15-deficient HCC cells were more susceptible to glutamine deprivation and glutaminase inhibitors. Intervening in glutamine metabolism increased SLC25A15-deficient HCC cells' response to anti-PD-L1 treatment. CONCLUSION: SLC25A15 is hypoxia-responsive in HCC, and low SLC25A15 levels result in glutamine reprogramming through SLC1A5 and OGDHL regulation, promoting HCC progression and regulating cell sensitivity to anti-PD-L1. Interrupting the glutamine-derived energy supply is a potential therapeutic strategy for treating SLC25A15-deficient HCC. IMPACT AND IMPLICATIONS: We first demonstrated the tumor suppressor role of solute carrier family 25 member 15 (SLC25A15) in hepatocellular carcinoma (HCC) and showed that its deficiency leads to reprogramming of glutamine metabolism to promote HCC development. SLC25A15 can serve as a potential biomarker to guide the development of precision therapeutic strategies aimed at targeting glutamine deprivation. Furthermore, we highlight that the use of an inhibitor of glutamine utilization can enhance the sensitivity of low SLC25A15 HCC to anti-PD-L1 therapy.

Temperature-insensitive high-sensitivity refractive index sensor based on a thinned helical fiber grating with an intermediate period.

A temperature-insensitive high-sensitivity refractive index sensor is proposed and experimentally demonstrated, which is based on utilization of a thinned helical fiber grating but with an intermediate period (THFGIP). Attributed to the reduced diameter and an intermediate period of the grating, the proposed sensor has a high surrounding refractive-index (SRI) sensitivity and a low temperature sensitivity. The average SRI sensitivity of the proposed sensor is up to 829.9 nm/RIU in the range of 1.3410-1.4480 RIU. Moreover, unlike the traditional sensitivity-enhancement method by increasing the waveguide dispersion factor, here the waveguide dispersion factor at the resonant wavelength was decreased by reducing the diameter of the fiber grating and as a result, the crosstalk effect due to the temperature change can be further suppressed. The proposed temperature-insensitive SRI sensor has the superiorities of simple structure, ease fabrication, and low cost, which could be found more potential applications in the SRI sensing fields.

Polymerization-Induced Self-Assembly Providing PEG-Gels with Dynamic Micelle-Crosslinked Hierarchical Structures and Overall Improvement of Their Comprehensive Performances.

Polymer gels are fascinating soft materials and have become excellent candidates for wearable electronics, biomedicine, sensors, etc. Synthetic gels usually suffer from poor mechanical properties, and integrating good mechanical properties, adhesiveness, stability, and self-healing performances in one gel is more difficult. Herein, polymerization-induced self-assembly (PISA) providing PEG-gels with an overall improvement in their comprehensive performances is reported. PISA synthesis is carried out in PEG (solvent) to efficiently produce various nanoparticles, which are used as the nanofillers in the subsequent synthesis of PEG-gels with dynamic micelle-crosslinked hierarchical structures. Compared to hydrogels, PEG-gels show excellent long-term stability due to the nonvolatile feature of PEG solvent. The hierarchical PEG-gels (with nanofillers) exhibit better mechanical and adhesive properties than the homogeneous-gels (without nanofillers). The energy dissipation mechanism of the PEG-gels is analyzed via stress relaxation and cyclic mechanical tests. High-density hydrogen bonds between the micelles and PAA matrix can be broken and reformed, endowing better self-healing properties of the dynamic micelle-crosslinked PEG gels. This work provides a simple strategy for producing hierarchical structural gels with enhanced properties, which offers fundamentals and inspirations for the designing of various advanced functional materials.

Burst-Enhanced Super-Resolution Network (BESR).

Multi-frame super-resolution (MFSR) leverages complementary information between image sequences of the same scene to increase the resolution of the reconstructed image. As a branch of MFSR, burst super-resolution aims to restore image details by leveraging the complementary information between noisy sequences. In this paper, we propose an efficient burst-enhanced super-resolution network (BESR). Specifically, we introduce Geformer, a gate-enhanced transformer, and construct an enhanced CNN-Transformer block (ECTB) by combining convolutions to enhance local perception. ECTB efficiently aggregates intra-frame context and inter-frame correlation information, yielding an enhanced feature representation. Additionally, we leverage reference features to facilitate inter-frame communication, enhancing spatiotemporal coherence among multiple frames. To address the critical processes of inter-frame alignment and feature fusion, we propose optimized pyramid alignment (OPA) and hybrid feature fusion (HFF) modules to capture and utilize complementary information between multiple frames to recover more high-frequency details. Extensive experiments demonstrate that, compared to state-of-the-art methods, BESR achieves higher efficiency and competitively superior reconstruction results. On the synthetic dataset and real-world dataset of BurstSR, our BESR achieves PSNR values of 42.79 dB and 48.86 dB, respectively, outperforming other MFSR models significantly.

Self-deception: Distorted metacognitive process in ambiguous contexts.

As one of the commonly used folk psychological concepts, self-deception has been intensively discussed yet is short of solid ground from cognitive neuroscience. Self-deception is a biased cognitive process of information to obtain or maintain a false belief that could be both self-enhancing or self-diminishing. Study 1 (N = 152) captured self-deception by adopting a modified numerical discrimination task that provided cheating opportunities, quantifying errors in predicting future performance (via item-response theory model), and measuring the belief of how good they are at solving the task (i.e., self-efficacy belief). By examining whether self-efficacy belief is based upon actual ability (true belief) or prediction errors (false belief), Study 1 showed that self-deception occurred in the effortless (easier access to answer cues) rather than effortful (harder access to answer cues) cheating opportunity conditions, suggesting high ambiguity in attributions facilitates self-deception. Studies 2 and 3 probed the neural source of self-deception, linking self-deception with the metacognitive process. Both studies replicated behavioral results from Study 1. Study 2 (ERP study; N = 55) found that the amplitude of frontal slow wave significantly differed between participants with positive/self-enhancing and negative/self-diminishing self-deceiving tendencies in incorrect predictions while remaining similar in correct predictions. Study 3 (functional magnetic resonance imaging study; N = 33) identified self-deceiving associated activity in the anterior medial prefrontal cortex and showed that effortless cheating context increased cheating behaviors that further facilitated self-deception. Our findings suggest self-deception is a false belief associated with a distorted metacognitive mental process that requires ambiguity in attributions of behaviors.

Efficacy of adjuvant TACE on the prognosis of patients with HCC after hepatectomy: a multicenter propensity score matching from China.

BACKGROUND: The survival benefit of adjuvant transarterial chemoembolization (TACE) in patients with hepatectomy for hepatocellular carcinoma (HCC) after hepatectomy remains controversial. We aimed to investigate the survival efficacy of adjuvant TACE after hepatectomy for HCC. METHODS: 1491 patients with HCC who underwent hepatectomy between January 2018 and September 2021 at four medical centers in China were retrospectively analyzed, including 782 patients who received adjuvant TACE and 709 patients who did not receive adjuvant TACE. Propensity score matching (PSM) (1:1) was performed to minimize selection bias, which balanced the clinical characteristics of the two groups. RESULTS: A total of 1254 patients were enrolled after PSM, including 627 patients who received adjuvant TACE and 627 patients who did not receive adjuvant TACE. Patients who received adjuvant TACE had higher disease-free survival (DFS, 1- ,2-, and 3-year: 78%-68%-62% vs. 69%-57%-50%, p < 0.001) and overall survival (OS, 1- ,2-, and 3-year: 96%-88%-80% vs. 90%-77%-66%, p < 0.001) than those who did not receive adjuvant TACE (Median DFS was 39 months). Among the different levels of risk factors affecting prognosis [AFP, Lymphocyte-to-monocyte ratio, Maximum tumor diameter, Number of tumors, Child-Pugh classification, Liver cirrhosis, Vascular invasion (imaging), Microvascular invasion, Satellite nodules, Differentiation, Chinese liver cancer stage II-IIIa], the majority of patients who received adjuvant TACE had higher DFS or OS than those who did not receive adjuvant TACE. More patients who received adjuvant TACE accepted subsequent antitumor therapy such as liver transplantation, re-hepatectomy and local ablation after tumor recurrence, while more patients who did not receive adjuvant TACE accepted subsequent antitumor therapy with TACE after tumor recurrence (All p < 0.05). CONCLUSIONS: Adjuvant TACE may be a potential way to monitor early tumor recurrence and improve postoperative survival in patients with HCC.

Development and Validation of a Nomogram for Predicting Postoperative Early Relapse and Survival in Hepatocellular Carcinoma.

BACKGROUND: Early relapse after hepatectomy presents a significant challenge in the treatment of hepatocellular carcinoma (HCC). The aim of this study was to construct and validate a novel nomogram model for predicting early relapse and survival after hepatectomy for HCC. PATIENTS AND METHODS: We conducted a large-scale, multicenter retrospective analysis of 1,505 patients with surgically treated HCC from 4 medical centers. All patients were randomly divided into either the training cohort (n=1,053) or the validation cohort (n=452) in a 7:3 ratio. A machine learning-based nomogram model for prediction of HCC was established by integrating multiple risk factors that influence early relapse and survival, which were identified from preoperative clinical data and postoperative pathologic characteristics of the patients. RESULTS: The median time to early relapse was 7 months, whereas the median time from early relapse to death was only 19 months. The concordance indexes of the postoperative nomogram for predicting disease-free survival and overall survival were 0.741 and 0.739, respectively, with well-calibrated curves demonstrating good consistency between predicted and observed outcomes. Moreover, the accuracy and predictive performance of the postoperative nomograms were significantly superior to those of the preoperative nomogram and the other 7 HCC staging systems. The patients in the intermediate- and high-risk groups of the model had significantly higher probabilities of early and critical recurrence (P<.001), whereas those in the low-risk group had higher probabilities of late and local recurrence (P<.001). CONCLUSIONS: This postoperative nomogram model can better predict early recurrence and survival and can serve as a useful tool to guide clinical treatment decisions for patients with HCC.

Design and Construction of Enzyme-Based Electrochemical Gas Sensors.

The demand for the ubiquitous detection of gases in complex environments is driving the design of highly specific gas sensors for the development of the Internet of Things, such as indoor air quality testing, human exhaled disease detection, monitoring gas emissions, etc. The interaction between analytes and bioreceptors can described as a "lock-and-key", in which the specific catalysis between enzymes and gas molecules provides a new paradigm for the construction of high-sensitivity and -specificity gas sensors. The electrochemical method has been widely used in gas detection and in the design and construction of enzyme-based electrochemical gas sensors, in which the specificity of an enzyme to a substrate is determined by a specific functional domain or recognition interface, which is the active site of the enzyme that can specifically catalyze the gas reaction, and the electrode-solution interface, where the chemical reaction occurs, respectively. As a result, the engineering design of the enzyme electrode interface is crucial in the process of designing and constructing enzyme-based electrochemical gas sensors. In this review, we summarize the design of enzyme-based electrochemical gas sensors. We particularly focus on the main concepts of enzyme electrodes and the selection and design of materials, as well as the immobilization of enzymes and construction methods. Furthermore, we discuss the fundamental factors that affect electron transfer at the enzyme electrode interface for electrochemical gas sensors and the challenges and opportunities related to the design and construction of these sensors.

Increasing the Diameter of Vertically Aligned, Hexagonally Ordered Pores in Mesoporous Silica Thin Films.

The variation in pore size in mesoporous films produced by electrochemically assisted self-assembly (EASA) with the surfactant chain length is described. EASA produces a hexagonal array of pores perpendicular to the substrate surface by using an applied potential to organize cationic surfactants and the resultant current to drive condensation in a silica sol. Here, we show that a range of pore sizes between 2 and 5 nm in diameter is available with surfactants of the form [Me3NCnH2n+1]Br, with alkyl chain lengths between C14 and C24. The film quality, pore order, pore size, and pore accessibility are probed with a range of techniques.

Greatly Enhanced Accessibility and Reproducibility of Worm-like Micelles by In Situ Crosslinking Polymerization-Induced Self-Assembly.

Worm-like micelles have attracted great interest due to their anisotropic structures. However, the experimental conditions for obtaining worm-like micelles are very restricted, which usually causes seriously poor reproducibility. In this work, significantly enhanced accessibility of worm-like micelles is realized by in situ crosslinking polymerization-induced self-assembly (PISA). The reproducibility of worm-like micelles is greatly improved due to the significantly enlarged experimental windows of worm-like micelles in the morphology diagram. Moreover, the reliability of the methodology to enhance the accessibility of worm-like micelles has been demonstrated in various in situ crosslinking PISA systems. The greatly enhanced accessibility and reproducibility of worm-like micelles is undoubtedly cost-effective especially in scale-up production, which paves the way for further application of worm-like micelles with various compositions and functionalities.

Randomly Distributed Sulfur Atoms in the Main Chains of CO2 -Based Polycarbonates: Enhanced Optical Properties.

Polymeric materials possessing both high refractive indices and high Abbe numbers are much in demand for the development of advanced optical devices. However, the synthesis of such functional materials is a challenge because of the trade-off between these two properties. Herein, a synthetic strategy is presented for enhancing the optical properties of CO2 -based polycarbonates by modifying the polymer's topological structure. Terpolymers with thiocarbonate and carbonate units randomly distributed in the polymers' main chain were synthesized via the terpolymerization of cyclohexene oxide with a mixture of CO2 and COS in the presence of metal catalysts, most notably a dinuclear aluminum complex. DFT calculations were employed to explain why different structural sequence were obtained with distinct bimetallic catalysts. Varying the CO2 pressure made it possible to obtain terpolymers with tunable carbonate linkages in the polymer chain. More importantly, optical property studies revealed that terpolymers with comparable thiocarbonate and carbonate units exhibited a refractive index of 1.501 with an enhanced Abbe number as high as 48.6, much higher than the corresponding polycarbonates or polythiocarbonates. Additionally, all terpolymers containing varying thiocarbonate content displayed good thermal properties with Tg >109 °C and Td >260 °C, suggesting little loss in the thermal stability compared to the polycarbonate. Hence, modification of the topological structure of the polycarbonate is an efficient method of obtaining polymeric materials with enhanced optical properties without compromising thermal performance.

Polymerization-Induced Self-Assembly to Produce Prodrug Nanoparticles with Reduction-Responsive Camptothecin Release and pH-Responsive Charge-Reversible Property.

Polymerization-induced self-assembly has been demonstrated to be a powerful strategy for fabricating polymeric nanoparticles in the last two decades. However, the stringent requirements for the monomers greatly limit the chemical versatility of PISA-based functional nanoparticles and expanding the monomer family of PISA is still highly desirable. Herein, a camptothecin analogue (CPTM) is first used as the monomer in PISA. Prodrug nanoparticles with reduction-responsive camptothecin release behavior are fabricated at 10% solid concentration (100 mg g-1 ). Poly(N-(2-hydroxypropyl)methacrylamide) (PHPMA) and poly(2-(diethylamino)ethyl methacrylate) (PDEAEMA) are used as the macro RAFT agents to comediate the RAFT dispersion polymerization of CPTM in ethanol to produce the PHPMA/PDEAEMA-stabilized nanoparticles. The PDEAEMA chains become hydrophobic and are in the collapsed state at physiological pH values. In contrast, in the vicinity of an acidic tumor, the tertiary amine groups of PDEAEMA chains are rapidly protonated, leading to fast hydrophobic-hydrophilic transitions and charge reversal. Such fast charge-reversal results in enhanced cancer cell internalization of the prodrug nanoparticles, thus achieving superior anticancer efficacy.

Facile Synthesis of Well-Defined Branched Sulfur-Containing Copolymers: One-Pot Copolymerization of Carbonyl Sulfide and Epoxide.

Topological polymers possess many advantages over linear polymers. However, when it comes to the poly(monothiocarbonate)s, no topological polymers have been reported. Described herein is a facile and efficient approach for synthesizing well-defined branched poly(monothiocarbonate)s in a "grafting through" manner by copolymerizing carbonyl sulfide (COS) with epichlorohydrin (ECH), where the side-chain forms in situ. The lengths of the side-chains are tunable based on reaction temperatures. More importantly, enhancement in thermal properties of the branched copolymer was observed, as the Tg  value increased by 22 °C, compared to the linear analogues. When chiral ECH was utilized, semicrystalline branched poly(monothiocarbonate)s were accessible with a Tm  value of 112 °C, which is 40 °C higher than that of the corresponding linear poly(monothiocarbonate)s. The strategy presented herein for synthesizing branched polymers provides efficient and concise access to topological polymers.

Towards a 3D GeSbTe phase change memory with integrated selector by non-aqueous electrodeposition.

We have recently reported a new method for the electrodeposition of thin film and nanostructured phase change memory (PCM) devices from a single, highly tuneable, non-aqueous electrolyte. The quality of the material was confirmed by phase cycling via electrical pulsed switching of both 100 nm nano-cells and thin film devices. This method potentially allows deposition into extremely small confined cells down to less than 5 nm, 3D lay-outs that require non-line-of-sight techniques, and seamless integration of selector devices. As electrodeposition requires a conducting substrate, the key condition for electronic applications based on this method is the use of patterned metal lines as the working electrode during the electrodeposition process. In this paper, we show the design and fabrication of a 2D passive memory matrix in which the word lines act as the working electrode and nucleation site for the growth of confined cells of Ge-Sb-Te. We will discuss the precursor requirement for deposition from non-aqueous, weakly coordinating solvents, show the transmission electron microscopy analysis of the electrodeposition growth process and elemental distribution in the deposits, and show the fabrication and characterisation of the Ge-Sb-Te memory matrix.

Polymerization-Induced Self-Assembly of Functionalized Block Copolymer Nanoparticles and Their Application in Drug Delivery.

Drug delivery systems (DDS) based on functionalized polymeric nanoparticles have attracted considerable attention. Although great advances have been reported in the past decades, the fabrication efficiency and reproducibility of polymeric nanoparticles are barely satisfactory due to the intrinsic limitations of the traditional self-assembly method, which severely prevent further applications of the intelligent DDS. In the last decade, a new self-assembly method, which is usually called polymerization-induced self-assembly (PISA), has become a powerful strategy for the fabrication of the polymeric nanoparticles with bespoke morphology. The PISA strategy efficiently simplifies the fabrication of polymeric nanoparticles (combination of the polymerization and self-assembly in one pot) and allows the fabrication of polymeric nanoparticles at a relatively high concentration (up to 50 wt%), making it realistic for large-scale production of polymeric nanoparticles. In this review, the developments of PISA-based polymeric nanoparticles for drug delivery are discussed.

Cone-Beam Computed Tomography Analysis of the Prevalence, Length, and Passage of the Anterior Loop of the Mandibular Canal.

When placing implants in the anterior mandible, it is important to avoid damaging the mandibular nerve and its terminal extensions. The objective of this study was to determine the prevalence, length, and passage of the anterior loop of the mandibular canal, as well as the quantity of alveolar bone that is coronal to the canal, to help with implant placement in the anterior mandible. Cone-beam computerized tomography (CBCT) scans of 124 patients with 248 hemi-sections were evaluated. Anterior loop prevalence was determined using reconstructed panoramic and cross-sectional views; length was measured as the distance between the most mesial aspect of the mental foramen to the most mesial aspect of the anterior loop on cross-sectional views. The bucco-lingual position of the anterior loop inside the mandible and the apico-coronal dimensions of the alveolar bone above it were measured on cross-sectional views to determine the passage of the anterior loop and the bone available coronally, respectively. The effects of sex, age, side, and dentate status on the prevalence and length of the anterior loop were analyzed statistically. Prevalence of the anterior loop at the patient and hemi-section levels was 25% and 24%, respectively, and its median length was 1.63 mm (range, 0.52-3.92 mm). The anterior loop was apical to the mental foramen and mostly located within the buccal or middle one-third of the alveolar ridge, with an average height of coronal alveolar bone of 17.12 mm. Sex, age, side, and dentate status did not affect anterior loop prevalence and length. In conclusion, because of great variation, a case-by-case CBCT evaluation of the anterior loop is necessary before placing implants in the anterior mandible.

Recombinant human GLP-1(rhGLP-1) alleviating renal tubulointestitial injury in diabetic STZ-induced rats.

GLP-1-based treatment improves glycemia through stimulation of insulin secretion and inhibition of glucagon secretion. Recently, more and more findings showed that GLP-1 could also protect kidney from diabetic nephropathy. Most of these studies focused on glomeruli, but the effect of GLP-1 on tubulointerstitial and tubule is not clear yet. In this study, we examined the renoprotective effect of recombinant human GLP-1 (rhGLP-1), and investigated the influence of GLP-1 on inflammation and tubulointerstitial injury using diabetic nephropathy rats model of STZ-induced. The results showed that rhGLP-1 reduced urinary albumin without influencing the body weight and food intake. rhGLP-1 could increased the serum C-peptide slightly but not lower fasting blood glucose significantly. In diabetic nephropathy rats, beside glomerular sclerosis, tubulointerstitial fibrosis was very serious. These lesions could be alleviated by rhGLP-1. rhGLP-1 decreased the expression of profibrotic factors collagen I, α-SMA, fibronectin, and inflammation factors MCP-1 and TNFα in tubular tissue and human proximal tubular cells (HK-2 cells). Furthermore, rhGLP-1 significantly inhibited the phosphorylation of NF-κB, MAPK in both diabetic tubular tissue and HK-2 cells. The inhibition of the expression of TNFα, MCP-1, collagen I and α-SMA in HK-2 cells by GLP-1 could be mimicked by blocking NF-κB or MAPK. These results indicate that rhGLP-1 exhibit renoprotective effect by alleviation of tubulointerstitial injury via inhibiting phosphorylation of MAPK and NF-κB. Therefore, rhGLP-1 may be a potential drug for treatment of diabetic nephropathy.

Exosomes of Endothelial Progenitor Cells Inhibit Neointima Formation After Carotid Artery Injury.

BACKGROUND: Exosomes released from endothelial progenitor cells (EPCs) play a protective role in various disease models. Both endothelial cell (EC) damage and smooth muscle cell (SMC) proliferation are involved in the pathological process of restenosis after angioplasty and stenting. Few studies have focused on the therapeutic role of exosomes in EC damage and SMC proliferation. In this study, we sought to investigate the effect of exosomes released by human fetal aorta-derived EPCs on the rat carotid artery balloon injury model in vivo. We also sought to determine the effect of exosomes on both ECs and SMCs in vitro. METHODS: Exosomes (Exo group) or saline (Con group) were injected in rat carotid balloon injury model animals. The rats were sacrificed after 2, 4, 14, and 28 d, and injured carotid specimens were collected for Evans blue staining, hematoxylin-eosin staining, and immunohistochemistry. RESULTS: When the Con group and the Exo group were compared, the reendothelialized areas were not significantly different after 2 or 4 d, as shown by Evans blue staining. The hematoxylin-eosin results showed that the intimal to medial area ratio was slightly but not significantly higher in the Exo group after 2 and 4 d. The immunohistochemistry results showed that the proliferation of SMCs was slightly higher in the Exo group after 2 and 4 d, but the difference was not significant. The reendothelialization area of the Con group was significantly smaller than that of the Exo group at day 14. Both the intimal to medial area ratio and SMC proliferation in the Exo group were significantly smaller than those of the Con group at 14 or 28 d. In the in vitro study, exosome treatment significantly enhanced the proliferation and migration of both ECs and SMCs. CONCLUSIONS: Exosomes derived from EPCs could inhibit neointimal hyperplasia after carotid artery injury in rats. The protective effect of exosomes may manifest through the promotion of EC repair rather than direct suppression of proliferation and migration of smooth muscles cells.

A retrospective study on molar furcation assessment via clinical detection, intraoral radiography and cone beam computed tomography.

BACKGROUND: Accurate determination of bone loss at the molar furcation region by clinical detection and intraoral radiograph is challenging in many instances. Cone beam computed tomography (CBCT) is expected to open a new horizon in periodontal assessment. The purpose of this study was to compare and correlate accuracy of molar furcation assessment via clinical detection, intraoral radiography and CBCT images. METHODS: Eighty-three patients with chronic periodontitis who had existing CBCT scans were included. Furcation involvement was assessed on maxillary and mandibular first molars. Periodontal charts (modified Glickman's classification), intraoral (periapical and/or bitewing) radiographs (recorded as presence or absence) and axial CBCT reconstructions were used to evaluate furcation involvement on buccal and palatal/lingual sites. The correlation of furcation assessment by the three methods was evaluated by Pearson analysis. RESULTS: There were significant correlations (p < 0.05) between clinical detection and intraoral radiography, clinical detection and CBCT, as well as intraoral radiography and CBCT at all the measured sites (r values range between 0.230 to 0.644). CBCT generally exhibited higher correlation with clinical detection relative to intraoral radiography, especially at distal palatal side of maxillary first molar (p < 0.05). In addition, CBCT provided more accurate assessment, with bone loss measurement up to 2 decimals in millimeters, whereas clinical detection had 3 classes and the intraoral radiographs usually only detected the presence of furcation involvement in Glickman Class 2 and 3. CONCLUSIONS: This study validates that CBCT is a valuable tool in molar furcation assessment in addition to clinical detection and intraoral radiography.

Transplantation of human fetal pancreatic progenitor cells ameliorates renal injury in streptozotocin-induced diabetic nephropathy.

BACKGROUND: Diabetic nephropathy (DN) is a severe complication of diabetes mellitus (DM). Pancreas or islet transplantation has been reported to prevent the development of DN lesions and ameliorate or reverse existing glomerular lesions in animal models. Shortage of pancreas donor is a severe problem. Islets derived from stem cells may offer a potential solution to this problem. OBJECTIVE: To evaluate the effect of stem cell-derived islet transplantation on DN in a rat model of streptozotocin-induced DM. METHODS: Pancreatic progenitor cells were isolated from aborted fetuses of 8 weeks of gestation. And islets were prepared by suspension culture after a differentiation of progenitor cells in medium containing glucagon-like peptide-1 (Glp-1) and nicotinamide. Then islets were transplanted into the liver of diabetic rats via portal vein. Blood glucose, urinary volume, 24 h urinary protein and urinary albumin were measured once biweekly for 16 weeks. Graft survival was evaluated by monitoring human C-peptide level in rat sera and by immunohistochemical staining for human mitochondrial antigen and human C-peptide in liver tissue. The effect of progenitor-derived islets on filtration membrane was examined by electron microscopy and real-time polymerase chain reaction (PCR). Immunohistochemical staining, real-time PCR and western blot were employed for detecting fibronectin, protein kinase C beta (PKCß), protein kinase A (PKA), inducible nitric oxide synthase (iNOS) and superoxide dismutase (SOD). RESULTS: Islet-like clusters derived from 8th gestational-week human fetal pancreatic progenitors survived in rat liver. And elevated serum level of human C-peptide was detected. Blood glucose, 24 h urinary protein and urinary albumin were lower in progenitor cell group than those in DN or insulin treatment group. Glomerular basement membrane thickness and fibronectin accumulation decreased significantly while podocytes improved morphologically in progenitor cell group. Furthermore, receptor of advanced glycation end products and PKCß became down-regulated whereas PKA up-regulated by progenitor cell-derived islets. And iNOS rose while SOD declined. CONCLUSIONS: DN may be reversed by transplantation of human fetal pancreatic progenitor cell-derived islets. And fetal pancreatic progenitor cells offer potential resources for cell replacement therapy.