Assessing the causal link between liver function and acute pancreatitis: A Mendelian randomisation study.

A correlation has been reported to exist between exposure factors (e.g. liver function) and acute pancreatitis. However, the specific causal relationship remains unclear. This study aimed to infer the causal relationship between liver function and acute pancreatitis using the Mendelian randomisation method. We employed summary data from a genome-wide association study involving individuals of European ancestry from the UK Biobank and FinnGen. Single-nucleotide polymorphisms (SCNPs), closely associated with liver function, served as instrumental variables. We used five regression models for causality assessment: MR-Egger regression, the random-effect inverse variance weighting method (IVW), the weighted median method (WME), the weighted model, and the simple model. We assessed the heterogeneity of the SNPs using Cochran's Q test. Multi-effect analysis was performed using the intercept term of the MR-Egger method and leave-one-out detection. Odds ratios (ORs) were used to evaluate the causal relationship between liver function and acute pancreatitis risk. A total of 641 SNPs were incorporated as instrumental variables. The MR-IVW method indicated a causal effect of gamma-glutamyltransferase (GGT) on acute pancreatitis (OR = 1.180, 95%CI [confidence interval]: 1.021-1.365, P = 0.025), suggesting that GGT may influence the incidence of acute pancreatitis. Conversely, the results for alkaline phosphatase (ALP) (OR = 0.997, 95%CI: 0.992-1.002, P = 0.197) and aspartate aminotransferase (AST) (OR = 0.939, 95%CI: 0.794-1.111, P = 0.464) did not show a causal effect on acute pancreatitis. Additionally, neither the intercept term nor the zero difference in the MR-Egger regression attained statistical significance (P = 0.257), and there were no observable gene effects. This study suggests that GGT levels are a potential risk factor for acute pancreatitis and may increase the associated risk. In contrast, ALP and AST levels did not affect the risk of acute pancreatitis.

Percutaneous radiofrequency thermocoagulation for trigeminal neuralgia using neuronavigation-guided puncture from a mandibular angle.

Percutaneous radiofrequency thermocoagulation (RFT) of the Gasserian ganglion is an effective treatment for primary trigeminal neuralgia (pTN). Currently Hartel anterior approach is the most commonly used method to access the Gasserian ganglion. However, this approach is associated with high recurrence rate and technical difficulties in certain patients with foramen ovale (FO) anatomical variations. In the present study, we assessed the feasibility of accessing the Gasserian ganglion through the FO from a mandibular angle under computed tomography (CT) and neuronavigation guidance.A total of 108 patients with TN were randomly divided into 2 groups (Group G and Group H) using a random number table. In Group H, Hartel anterior approach was used to puncture the FO; whereas in Group G, a percutaneous puncture through a mandibular angle was used to reach the FO. In both groups, procedures were guided by CT imaging and neuronavigation. The success rates, therapeutic effects, complications, and recurrence rates of the 2 groups were compared.The puncture success rates in Group H and Group G were 52/54 (96.30%) and 49/54 (90.74%), respectively (P = 0.24). The 2 procedural failures in Group H were rescued by using submandibular trajectory, and the 5 failures in Group G were successfully reapproached by Hartel method. Therapeutic effects as measured by Barrow Neurological Institute (BNI) pain scale (P = 0.03) and quality of life (QOL) scores (P = 0.04) were significantly better in Group G than those in Group H at 36 months posttreatment. Hematoma developed in 1/54 (1.85%) cases in Group H, and no cases of hematoma were observed in Group G (P = 0.33). In Group H, RFT resulted in injury to the unintended trigeminal nerve branches and motor fibers in 27/52 (51.92%) cases; in Group G, it resulted in the same type of injury in 7/49 cases (14.29%) (P < 0.01). In Group H, the 24- and 36-month recurrence rates were 12/51 (23.53%) and 20/51 (39.22%), respectively; in Group G, these recurrence rates were 7/49 (12.24%) and 9/49 (16.33%, P = 0.03), respectively.CT- and neuronavigation-guided puncture from a mandibular angle through the FO into the Gasserian ganglion can be safely and effectively used to deliver RFT for the treatment of pTN. This method may represent a viable option to treat TN in addition to Hartel approach.

Cortisol Response to Psychosocial Stress in Chinese Early Puberty Girls: Possible Role of Depressive Symptoms.

Objective. The present study aimed at investigating unique patterns of salivary cortisol reactivity and recovery in response to a social stressor among girls with early puberty and exploring possible role of depressive symptom in this association. Design. Case-control study. Patients. Fifty-six girls with early puberty and age- and body mass index- (BMI-) matched normal puberty controls (n = 56) were selected. Measurements. Salivary cortisol was measured in response to the Groningen Social Stress Test for Children. Results. Girls with early puberty had higher cortisol concentration at the end of the GSST (C3), cortisol concentration 20 min after the end of the GSST (C4), and AUC increment (AUCi) compared to non-early puberty girls. Depressive symptoms correlated with blunted HPA reactivity among girls with early puberty. Conclusion. This study demonstrated the disturbance effect of objectively examined early pubertal timing on HPA axis responses. It also suggested that stress reactivity might be blunted for individuals with depressive symptoms.

Connexin: a potential novel target for protecting the central nervous system?

Connexin subunits are proteins that form gap junction channels, and play an important role in communication between adjacent cells. This review article discusses the function of connexins/hemichannels/gap junctions under physiological conditions, and summarizes the findings regarding the role of connexins/hemichannels/gap junctions in the physiological and pathological mechanisms underlying central nervous system diseases such as brain ischemia, traumatic brain and spinal cord injury, epilepsy, brain and spinal cord tumor, migraine, neuroautoimmune disease, Alzheimer's disease, Parkinson's disease, X-linked Charcot-Marie-Tooth disease, Pelizaeus-Merzbacher-like disease, spastic paraplegia and maxillofacial dysplasia. Connexins are considered to be a potential novel target for protecting the central nervous system.

Canonical Wnt signaling acts synergistically on BMP9-induced osteo/odontoblastic differentiation of stem cells of dental apical papilla (SCAPs).

Dental pulp/dentin regeneration using dental stem cells combined with odontogenic factors may offer great promise to treat and/or prevent premature tooth loss. Here, we investigate if BMP9 and Wnt/ß-catenin act synergistically on odontogenic differentiation. Using the immortalized SCAPs (iSCAPs) isolated from mouse apical papilla tissue, we demonstrate that Wnt3A effectively induces early osteogenic marker alkaline phosphatase (ALP) in iSCAPs, which is reduced by ß-catenin knockdown. While Wnt3A and BMP9 enhance each other's ability to induce ALP activity in iSCAPs, silencing ß-catenin significantly diminishes BMP9-induced osteo/odontogenic differentiation. Furthermore, silencing ß-catenin reduces BMP9-induced expression of osteocalcin and osteopontin and in vitro matrix mineralization of iSCAPs. In vivo stem cell implantation assay reveals that while BMP9-transduced iSCAPs induce robust ectopic bone formation, iSCAPs stimulated with both BMP9 and Wnt3A exhibit more mature and highly mineralized trabecular bone formation. However, knockdown of ß-catenin in iSCAPs significantly diminishes BMP9 or BMP9/Wnt3A-induced ectopic bone formation in vivo. Thus, our results strongly suggest that ß-catenin may play an important role in BMP9-induced osteo/ondontogenic signaling and that BMP9 and Wnt3A may act synergistically to induce osteo/odontoblastic differentiation of iSCAPs. It's conceivable that BMP9 and/or Wnt3A may be explored as efficacious biofactors for odontogenic regeneration and tooth engineering.

Bone morphogenetic protein-9 effectively induces osteo/odontoblastic differentiation of the reversibly immortalized stem cells of dental apical papilla.

Dental pulp/dentin regeneration using dental stem cells combined with odontogenic factors may offer great promise to treat and/or prevent premature tooth loss. We previously demonstrated that bone morphogenetic protein 9 (BMP9) is one of the most potent factors in inducing bone formation. Here, we investigate whether BMP9 can effectively induce odontogenic differentiation of the stem cells from mouse apical papilla (SCAPs). Using a reversible immortalization system expressing SV40 T flanked with Cre/loxP sites, we demonstrate that the SCAPs can be immortalized, resulting in immortalized SCAPs (iSCAPs) that express mesenchymal stem cell markers. BMP9 upregulates Runx2, Sox9, and PPARγ2 and odontoblastic markers, and induces alkaline phosphatase activity and matrix mineralization in the iSCAPs. Cre-mediated removal of SV40 T antigen decreases iSCAP proliferation. The in vivo stem cell implantation studies indicate that iSCAPs can differentiate into bone, cartilage, and, to lesser extent, adipocytes upon BMP9 stimulation. Our results demonstrate that the conditionally iSCAPs not only maintain long-term cell proliferation but also retain the ability to differentiate into multiple lineages, including osteo/odontoblastic differentiation. Thus, the reversibly iSCAPs may serve as an important tool to study SCAP biology and SCAP translational use in tooth engineering. Further, BMP9 may be explored as a novel and efficacious factor for odontogenic regeneration.

Adenovirus-mediated gene transfer in mesenchymal stem cells can be significantly enhanced by the cationic polymer polybrene.

Mesenchymal stem cells (MSCs) are multipotent progenitors, which can undergo self-renewal and give rise to multi-lineages. A great deal of attentions have been paid to their potential use in regenerative medicine as potential therapeutic genes can be introduced into MSCs. Genetic manipulations in MSCs requires effective gene deliveries. Recombinant adenoviruses are widely used gene transfer vectors. We have found that although MSCs can be infected in vitro by adenoviruses, high virus titers are needed to achieve high efficiency. Here, we investigate if the commonly-used cationic polymer Polybrene can potentiate adenovirus-mediated transgene delivery into MSCs, such as C2C12 cells and iMEFs. Using the AdRFP adenovirus, we find that AdRFP transduction efficiency is significantly increased by Polybrene in a dose-dependent fashion peaking at 8 µg/ml in C2C12 and iMEFs cells. Quantitative luciferase assay reveals that Polybrene significantly enhances AdFLuc-mediated luciferase activity in C2C12 and iMEFs at as low as 4 µg/ml and 2 µg/ml, respectively. FACS analysis indicates that Polybrene (at 4 µg/ml) increases the percentage of RFP-positive cells by approximately 430 folds in AdRFP-transduced iMEFs, suggesting Polybrene may increase adenovirus infection efficiency. Furthermore, Polybrene can enhance AdBMP9-induced osteogenic differentiation of MSCs as early osteogenic marker alkaline phosphatase activity can be increased more than 73 folds by Polybrene (4 µg/ml) in AdBMP9-transduced iMEFs. No cytotoxicity was observed in C2C12 and iMEFs at Polybrene up to 40 µg/ml, which is about 10-fold higher than the effective concentration required to enhance adenovirus transduction in MSCs. Taken together, our results demonstrate that Polybrene should be routinely used as a safe, effective and inexpensive augmenting agent for adenovirus-mediated gene transfer in MSCs, as well as other types of mammalian cells.

Visible-light photocatalytic degradation performances and thermal stability due to the synergetic effect of TiO2 with conductive copolymers of polyaniline and polypyrrole.

Conductive polypyrrole-polyaniline/TiO2 nanocomposites (PPy-PANI/TiO2) were prepared by in situ oxidative copolymerization of pyrrole and aniline monomers in the presence of TiO2. For comparison studies, polypyrrole/TiO2 (PPy/TiO2) and polyaniline/TiO2 (PANI/TiO2) were also prepared. The samples were characterized by X-ray diffraction, transmission electron microscopy, UV-vis diffuse reflectance spectroscopy, zeta potential analysis, Fourier transform infrared spectroscopy, thermogravimetric analysis and photocurrent tests. In contrast to PPy/TiO2 and PANI/TiO2, PPy-PANI/TiO2 exhibits obvious absorption in the visible-light range, and is much superior to PPy/TiO2 and PANI/TiO2 in thermal stability. It is found that PPy-PANI/TiO2 performs well in the visible-light photocatalytic degradation of 4-nitrophenol. The optimized pyrrole : aniline : TiO2 molar ratio for best performance is 0.75 : 0.25 : 100. The efficacy of PPy-PANI/TiO2 is attributed to its conductivity, conjugated structure, as well as to the synergy amidst polypyrrole, polyaniline and TiO2.