Comparative Evaluation of Efficiency of Different Endodontic File Systems; Protaper Universal, MTWO, Protaper Next, Trunatomy, I-Race in Terms of Remaining Dentin Thickness: An In vitro CBCT Analysis.

Introduction: The longevity of an endodontically treated tooth depends on fracture resistance by preserving more remaining dentin thickness. The aim of this study is to determine which file system preserves more remaining dentin thickness. Materials and Methods: Protaper universal, M-two, Protaper Next, Trunatomy, I-Race and mandibular first premolar. The removed dentin thickness during instrumentation of each file system was noted by taking the difference of RDT of pre-instrumentation and post-instrumentation with the aid of CBCT. Results and Discussion: TRN [Group-4] shows the least aggressive cutting with maximal preservation of remaining dentin thickness at 3 mm and 6 mm from the apex at both mesiodistal and buccolingual dimensions. M-two [Group-2] shows maximum removed dentin thickness at 3 mm from the apex both mesiodistal dimension and buccolingual dimension. PTU [Group-1] shows maximum removed dentin thickness at 6 mm from the apex at mesiodistal dimension. M-two [Group-2] shows maximum removed dentin thickness at 6 mm from the apex at the buccolingual dimension. Conclusion: In this study, it is concluded that the Trunatomy file system preserves more remaining dentin thickness both mesiodistally and buccolingually both 3 mm and 6 mm from the apex.

Activity of cat premotor cortex neurons during visually guided stepping.

Visual control of steps is critical in everyday life. Several motor centers are implicated in visual control of steps on a complex surface, however, participation of a large cortical motor area, the premotor cortex, in visual guidance of steps during overground locomotion has not been examined. Here, we analyzed the activity of neurons in feline premotor cortex areas 6aα and 6aγ as cats walked on the flat surface where visual guidance of steps is not needed and stepped on crosspieces of a horizontally placed ladder or over barriers where visual control of steps is required. The comparison of neuronal firing between vision-dependent and vision-independent stepping revealed components of the activity related to visual guidance of steps. We found that the firing activity of 59% of neurons was modulated with the rhythm of strides on the flat surface, and the activity of 83-86% of the population changed upon transition to locomotion on the ladder or with barriers. The firing rate and the depth of the stride-related activity modulation of 33-44% of neurons changed, and the stride phases where neurons preferred to fire changed for 58-73% of neurons. These results indicate that a substantial proportion of areas 6aα and 6aγ neurons is involved in visual guidance of steps. Compared with the primary motor cortex, the proportion of cells, the firing activity of which changed upon transition from vision-independent to vision-dependent stepping, was lower and the preferred phases of the firing activity changed more often between the tasks.NEW & NOTEWORTHY Visual control of steps is critical for daily living, however, how it is achieved is not well understood. Here, we analyzed how neurons in the premotor cortex respond to the demand for visual control of steps on a complex surface. We conclude that premotor cortex neurons participate in the cortical network supporting visual control of steps by modifying the phase, intensity, and salience of their firing activity.

Pleiotrophin Signals Through ALK Receptor to Enhance the Growth of Neurons in the Presence of Inhibitory Chondroitin Sulfate Proteoglycans.

Chondroitin sulfate proteoglycans (CSPGs), one of the major extracellular matrix components of the glial scar that surrounds central nervous system (CNS) injuries, are known to inhibit the regeneration of neurons. This study investigated whether pleiotrophin (PTN), a growth factor upregulated during early CNS development, can overcome the inhibition mediated by CSPGs and promote the neurite outgrowth of neurons in vitro. The data showed that a CSPG matrix inhibited the outgrowth of neurites in primary cortical neuron cultures compared to a control matrix. PTN elicited a dose-dependent increase in the neurite outgrowth even in the presence of the growth inhibitory CSPG matrix, with optimal growth at 15 ng mL-1 of PTN (114.8% of neuronal outgrowth relative to laminin control). The growth-promoting effect of PTN was blocked by inhibition of the receptor anaplastic lymphoma kinase (ALK) by alectinib in a dose-dependent manner. Neurite outgrowth in the presence of this CSPG matrix was induced by activation of the protein kinase B (AKT) pathway, a key downstream mediator of ALK activation. This study identified PTN as a dose-dependent regulator of neurite outgrowth in primary cortical neurons cultured in the presence of a CSPG matrix and identified ALK activation as a key driver of PTN-induced growth.

Single-cell RNA sequencing reveals the mediatory role of cancer-associated fibroblast PTN in hepatitis B virus cirrhosis-HCC progression.

BACKGROUND: Cancer-associated fibroblasts (CAFs) are essential stromal components in the tumor microenvironment of hepatocellular carcinoma (HCC). Hepatitis B virus (HBV) infection induces pathological changes such as liver fibrosis/cirrhosis and HCC. The aim of this research was to explore the novel mediators of CAFs to modulate HBV cirrhosis-HCC progression. METHODS: The single-cell transcriptome data of HCC were divided into subsets, and the significant subset related to fibrotic cells, along with biological function, and clinical information of HCC was revealed by integrated data analyses. The cell communication, cells communicated weight analysis of signaling pathways, and key genes in signaling pathways analysis of significant CAFs subclasses were conducted to discover the novel gene of CAFs. Bioinformatics, vitro and HBV transfection assays were used to verify the novel gene is an important target for promoting the progression HBV cirrhosis-HCC progression. RESULTS: Fibroblasts derived from HCC single-cell data could be separated into three cell subclasses (CAF0-2), of which CAF2 was associated with the HCC clinical information. Fibroblasts have opposite developmental trajectories to immune B cells and CD8 + T cells. CAF0-2 had strong interaction with B cells and CD8 + T cells, especially CAF2 had the highest interaction frequency and weight with B cells and CD8 + T cells. Moreover, PTN participated in CAF2-related pathways involved in the regulation of cell communication, and the interactions among CAF2 and PTN contributed the most to B cells and CD8 + T cells. Furthermore, the genes of PTN, SDC1, and NCL from PTN signaling were highest expression in CAF2, B cells, and CD8 + T cells, respectively, and the interaction of PTN- SDC1 and PTN- NCL contributed most to the interaction of CAF2- B cells and CAF2-CD8 + T cells. Bioinformatics and vitro experiments confirm PTN was upregulated in HCC and promoted the proliferation of tumor cells, and HBV infection could initiate PTN to perform cirrhosis-HCC progression. CONCLUSION: Our findings revealed CAF was associated with hepatocarcinogenesis, and the functional importance of B cells and CD8 + T cells in modulating CAF in HCC. Importantly, PTN maybe a novel mediator of CAF to mediate HBV cirrhosis-HCC progression.

Intranasal administration of polysulfide prevents neurodegeneration in spinal cord and rescues mice from delayed paraplegia after spinal cord ischemia.

BACKGROUND: Delayed paraplegia is a devastating complication of thoracoabdominal aortic surgery. Hydrogen sulfide (H2S) was reported to be protective in a mouse model of spinal cord ischemia and the beneficial effect of H2S has been attributed to polysulfides. The objective of this study was to investigate the effects of polysulfides on delayed paraplegia after spinal cord ischemia. METHODS AND RESULTS: Spinal cord ischemia was induced in male and female C57BL/6J mice by clamping the aortic arch and the left subclavian artery. Glutathione trisulfide (GSSSG), glutathione (GSH), glutathione disulfide (GSSG), or vehicle alone was administered intranasally at 0, 8, 23, and 32 h after surgery. All mice treated with vehicle alone developed paraplegia within 48 h after surgery. GSSSG, but not GSH or GSSG, prevented paraplegia in 8 of 11 male mice (73%) and 6 of 8 female mice (75%). Intranasal administration of 34S-labeled GSSSG rapidly increased 34S-labeled sulfane sulfur species in the lumbar spinal cord. In mice treated with intranasal GSSSG, there were increased sulfane sulfur levels, and decreased neurodegeneration, microglia activation, and caspase-3 activation in the lumbar spinal cord. In vitro studies using murine primary cortical neurons showed that GSSSG increased intracellular levels of sulfane sulfur. GSSSG, but not GSH or GSSG, dose-dependently improved cell viability after oxygen and glucose deprivation/reoxygenation (OGD/R). Pantethine trisulfide (PTN-SSS) also increased intracellular sulfane sulfur and improved cell viability after OGD/R. Intranasal administration of PTN-SSS, but not pantethine, prevented paraplegia in 6 of 9 male mice (66%). CONCLUSIONS: Intranasal administration of polysulfides rescued mice from delayed paraplegia after transient spinal cord ischemia. The neuroprotective effects of GSSSG were associated with increased levels of polysulfides and sulfane sulfur in the lumbar spinal cord. Targeted delivery of sulfane sulfur by polysulfides may prove to be a novel approach to the treatment of neurodegenerative diseases.

Pt-N Co-Modified TiO2 Nanotube Electrode Photoelectrocatalytic Degradation of Oxytetracycline in Simulated Wastewater.

Using photodeposition and plasma, Pt-N co-modified TiO2 nanotube electrodes were created. Several techniques, such as SEM, XRD, UV-VIS-DRS, XPS, and PL, were used to analyze the electrode shape, crystalline structure, light absorption range, elemental composition, and photogenerated carrier recombination efficiency. Using the electrochemical workstation, EIS and I-t were utilized to examine the electrochemical characteristics. The results indicated that the diameter of the TiO2 nanotube tubes was around 90 nm, and that the photodeposition duration affected the amount of Pt particles deposited. The deposited Pt particles efficiently reduced the photogenerated carrier complexation rate of the N-TiO2 nanotube electrode, contributing to the separation of electron-hole pairs and light utilization. Electrochemical studies indicated that Pt-N co-modified TiO2 increased the electrode's oxidation and electrical conductivity, as well as its photoelectrocatalytic capacity. Oxytetracycline degradation in simulated wastewater by a Pt-N co-modified TiO2 nanotube electrode revealed the exceptional PEC activity, and the oxytetracycline degradation processes followed primary kinetics. •O2- and •OH played a significant role in the photoelectrocatalytic degradation of oxytetracycline, resulting in a novel method for oxytetracycline degradation.

Ubiquitin ligase Triad1 promotes neurite outgrowth by inhibiting MDM2-mediated ubiquitination of the neuroprotective factor pleiotrophin.

Spinal cord injury (SCI) is the most severe result of spine injury, but no effective therapy exists to treat SCI. We have previously shown that the E3 ubiquitin ligase Two RING fingers and DRIL 1 (Triad1) promotes neurite outgrowth after SCI. However, the mechanism by which Triad1 affects neuron growth and the potential involvement of its ubiquitination activity is unclear. Neuroprotective cytokine pleiotrophin (PTN) can promote microglia proliferation and neurotrophic factor secretion to achieve neuroprotection. We find using immunostaining and behavioral assays in rats that the expression of Triad1 and the PTN was peaked at 1 day after SCI and Triad1 improved motor function and histomorphological injury after SCI. We show using flow cytometry and astrocyte/neuronal coculture assays that Triad1 overexpression promoted PTN protein levels, neurotrophic growth factor (NGF) expression, brain-derived neurotrophic factor (BDNF) expression, astrocyte and neuronal viability, and neurite outgrowth but suppressed astrocyte apoptosis, while shRNA-mediated knockdown of Triad1 and PTN had the opposite effects. Ubiquitin ligase murine double mutant 2 (MDM2) has previously been demonstrated to participate in the process of neurite outgrowth and mediate ubiquitination of p53. Furthermore, we demonstrate overexpression of MDM2 downregulated PTN protein levels, NGF expression and BDNF expression in astrocytes, and inhibited neurite outgrowth of neurons. In addition, MDM2 facilitated PTN ubiquitination, which was reversed by Triad1. Finally, we show simultaneous sh-PTN and MDM2 overexpression attenuated the neurite outgrowth-promoting effect of Triad1 overexpression. In conclusion, we propose Triad1 promotes astrocyte-dependent neurite outgrowth to accelerate recovery after SCI by inhibiting MDM2-mediated PTN ubiquitination.

Comparison of the fracture resistance of the teeth prepared with ProTaper Universal, ProTaper Next, and ProTaper Gold rotary files.

OBJECTIVES: Root canal preparation can lead to cracks on the roots by creating stresses on the root canal walls, which decreases the fracture resistance of the tooth. The present study compared the fracture resistance of the teeth prepared by the ProTaper Universal (PTU), ProTaper Next (PTN), and ProTaper Gold (PTG) rotary file systems. MATERIALS AND METHODS: Fifty-six single-canal premolar teeth were sectioned 14 mm from the root apex. The roots were standardized based on the buccolingual and mesiodistal diameter and randomly assigned to three experimental (n = 14) and one control group (n = 14). The teeth in three experimental groups were instrumented with PTU, PTN, and PTG rotary files. The roots in the control group were not instrumented. A vertical force was applied to each root in a universal testing machine until the root fractured. The data were statistically analyzed by one-way analysis of variance. RESULTS: There was no significant difference in the fracture resistance of the teeth between the control, PTU, PTN, and PTG groups (p = .115). CONCLUSIONS: Root canal preparation with ProTaper files manufactured with conventional NiTi (PTU) and heat-treated alloys (PTN and PTG) did not affect the fracture resistance of teeth.

In-vivo protein nitration facilitates Vibrio cholerae cell survival under anaerobic, nutrient deprived conditions.

Protein tyrosine nitration (PTN), a highly selective post translational modification, occurs in both prokaryotic and eukaryotic cells under nitrosative stress. However, its physiological function is not yet clear. Like many gut pathogens, Vibrio cholerae also faces nitrosative stress, which makes its proteome more vulnerable to PTN. Here, we report for the first time in-vivo PTN in V. cholerae by immunoblotting and LC-ESI-MS/MS proteomic analysis. Our results indicated that in-vivo PTN in V. cholerae was culture media independent. Surprisingly, in-vivo PTN was reduced in V. cholerae proteome under anaerobic or hypoxic condition in a nutrient deprived state. Interestingly, intracellular nitrate content was more than the nitrite content in V. cholerae under anaerobic conditions. Additionally, biochemical measurement of GSH/GSSG ratio, activities of catalase and SOD, ROS and RNS imaging by confocal microscopy confirmed a relative intracellular oxidizing environment in V. cholerae under anaerobic conditions. This altered redox environment favors the oxidation of nitrite which may be generated from protein denitration enriching the intracellular nitrate pool. The cell survival of V. cholerae can finally be facilitated by nitrate reductase (NapA) utilizing that nitrate pool. Our cell viability study using wild type and ΔnapA strain of V. cholerae also supported the role of NapA mediated cell survival under nutrient deprived anaerobic conditions. In spite of having nitrate reductase (NapA), V. cholerae lacks any nitrite reductase (NiR). Hence, in-vivo nitration may provide an avenue for toxic nitrite storage and also may help in nitrosative stress tolerance mechanism preventing further unnecessary protein nitration in V. cholerae proteome.

LncRNA PITPNA-AS1/miR-223-3p/PTN axis regulates malignant progression and stemness in lung squamous cell carcinoma.

BACKGROUND: Long noncoding RNAs (lncRNAs) are a kind of molecule that cannot code proteins, and their expression is dysregulated in diversified cancers. LncRNA PITPNA-AS1 has been shown to act as a tumor promoter in a variety of malignancies, but its function and regulatory mechanisms in lung squamous cell carcinoma (LUSC) are yet unknown. METHODS: The mRNA and protein expression of genes were examined by RT-qPCR, western blot, and IHC assay. The cell proliferation, migration, invasion, and stemness were detected through CCK-8, colony formation, Transwell and spheroid formation assays. The CD44+ and CD166+ -positive cells were detected through flow cytometry. The binding ability among genes through luciferase reporter and RNA pull-down assays. The tumor growth was detected through in vivo nude mice assay. RESULTS: The lncRNA PITPNA-AS1 had increased expression in LUSC and was linked to a poor prognosis. In LUSC, PITPNA-AS1 also enhanced cell proliferation, migration, invasion, and stemness. This mechanistic investigation showed that PITPNA-AS1 absorbed miR-223-3p and that miR-223-3p targeted PTN. MiR-223-3p inhibition or PTN overexpression might reverse the inhibitory effects of PITPNA-AS1 suppression on LUSC progression, as demonstrated by rescue experiments. In addition, the PITPNA-AS1/miR-223-3p/PTN axis accelerated tumor development in vivo. CONCLUSIONS: It is the first time we investigated the potential role and ceRNA regulatory mechanism of PITPNA-AS1 in LUSC. The data disclosed that PITPNA-AS1 upregulated PTN through sponging miR-223-3p to enhance the onset and progression of LUSC. These findings suggested the ceRNA axis may serve as a promising therapeutic biomarker for LUSC patients.

Luteolin attenuates the chemoresistance of osteosarcoma through inhibiting the PTN/ß-catenin/MDR1 signaling axis by upregulating miR-384.

Multidrug resistance (MDR) remains a critical bottleneck in successful treatment of osteosarcoma (OS). Luteolin is a flavonoid compound that has been verified to increase the sensitivity to antineoplastic drugs in many tumors. However, its roles in reversing MDR of OS and the potential underlying mechanisms remain largely unknown. In this study, we demonstrated that luteolin enhances cellular chemosensitivity to doxorubicin and cisplatin both in OS cells and xenograft models, and it could increase the miR-384 level and downregulate the PTN expression. Additionally, target analysis confirmed that miR-384 directly modulates PTN expression, and subsequent mechanistic analysis verified that miR-384 could inhibit the MDR of OS cells through suppressing the PTN/ß-catenin/MDR1 signaling axis. Further analysis revealed treatment of sensitive MG63 cells with luteolin effectively packaged miR-384 into secreted exosomes and the exosomes could improve doxorubicin response in doxorubicin-resistant MG63/DOX cells. Our study confirmed that luteolin exerts MDR reversal effect against OS cells by regulating PTN expression via miR-384 and it may be a promising therapeutic agent for chemoresistant OS via its targeting of the PTN/ß-catenin/MDR1 axis.

Risk factors of herpes simplex virus reactivation after surgery for primary trigeminal neuralgia.

The objective of this study is to investigate the risk factors of oral or facial herpes simplex virus (HSV-1) infection after primary trigeminal neuralgia (PTN). The clinical data of 33 PTN patients admitted by the same surgeon in the neurosurgery were retrospectively analyzed. Among the 33 patients, 26 patients underwent microvascular decompression (MVD), 6 patients who have not been found the clear offending vessels during the operation underwent partial sensory rhizotomy (PSR), and only one underwent adhesive band separation. Thirteen patients with postoperative oral and facial HSV-1 infection were selected as the herpes group, and the remaining 20 patients without postoperative oral and facial HSV-1 infection were selected as the non-herpes group. The differences between the two groups were compared by statistical analysis of factors such as gender, age, operation mode, operation time, and serum HSV-1 antibody titer value before surgery. Compared with the non-herpes group, there were no statistically significant differences in sex ratio (P = 0.930), age composition (P = 0.261), or disease profile (P = 0.226). Twenty-six patients underwent MVD operation, eight of whom were infected, and the difference between the two groups was statistically significant (P = 0.029). The operation time of the herpes group was 10-30 min, which was significantly longer than that of the non-herpes group. The difference in operation time between the two groups was statistically significant (P = 0.023). Serum HSV-1-IgM was negative (< 0.9 COI) in all patients before surgery, but the positive rate of HSV-1-IgG (≥ 1.1 COI) was 97%, and the titer was greater than four times in 97% (32/33) of patients. The titer of IgG antibody in the herpes group was significantly lower than that in the non-herpes group, and the difference between the two groups was statistically significant (P = 0.017). The serum HSV-1-IgG in most of the PTN patients was positive. Latent HSV-1 in the trigeminal ganglion may be reactivate after PTN surgery to produce ipsilateral oral and facial herpes infection. The infection of HSV-1 reactivation after PTN surgery was positively correlated with the operation time but negatively correlated with the titer of HSV-1-IgG antibody before PTN surgery. The incidence of HSV-1 infection after PTN operation is related to different surgical procedures.

circ_PTN contributes to -cisplatin resistance in glioblastoma via PI3K/AKT signaling through the miR-542-3p/PIK3R3 pathway.

Glioblastoma has been identified as the most common and aggressive primary brain tumor in adults. Recently, it has been found that cisplatin (DDP) treatment is a common chemotherapeutic method for GBM patients. circ_PTN (ID number: hsa_circ_0003949) is a newly found circular (circRNA) which has been proved to be highly expressed in GBM cells, while its role in GBM remains unclear. Therefore, our study focused on investigating the role of circ_PTN in the DDP resistance of GBM cells. The expression of circ_PTN in DDP-sensitive and DDP-resistant GBM cells was detected in our assay. Functional experiments were utilized to unveil the effects of circ_PTN on the DDP resistance of GBM cells. Moreover, mechanism assays were conducted to confirm the mechanism of how circ_PTN affected the DDP resistance of GBM cells. According to the results, we found that circ_PTN promoted the DDP resistance of GBM cells through activation of the PI3K/AKT pathway. Moreover, circ_PTN silencing inhibited the DDP resistance of GBM tumors in vivo. To conclude, our study unveiled the influence of circ_PTN on the DDP resistance of GBM cells, which might provide a therapeutic target for GBM treatment via DDP.

Genetic inactivation of midkine, not pleiotrophin, facilitates extinction of alcohol-induced conditioned place preference.

Pleiotrophin (PTN) and midkine (MK) are growth factors that modulate alcohol consumption and reward. Since both PTN and MK limit the rewarding effects of alcohol, pharmacological potentiation of the PTN and MK signaling pathways has been proposed for the treatment of alcohol use disorders (AUD). Although the use of this therapy in the prevention of alcohol relapse is important, the potential role of these cytokines in extinguishing alcohol-induced seeking behavior is a key question that remains unanswered. To fill this gap, we have now studied the extinction of the conditioned place preference (CPP) induced by different doses of alcohol in Ptn knockout (Ptn-/-) and Mk knockout (Mk-/-) mice. The data confirm a higher sensitivity of Ptn-/- mice to the conditioning effects of a low dose (1 g/kg) and a rewarding dose (2 g/kg) of alcohol, while Mk-/- mice are only more susceptible to the conditioning effects of the low dose of this drug. More importantly, the percentage of Mk-/- mice, not Ptn-/- mice, that efficiently extinguished alcohol-induced CPP was significantly higher than that of Wt mice. Taken together, the data presented here confirm that Ptn and Mk are genetic factors that determine the conditioning effects of alcohol in mice and that Mk is a novel factor that plays an important role in the extinction of alcohol-induced CPP.

The ERK/CREB/PTN/syndecan-3 pathway involves in heparin-mediated neuro-protection and neuro-regeneration against cerebral ischemia-reperfusion injury following cardiac arrest.

BACKGROUND: Heparin, a commonly used anticoagulant, has been found to improve cerebral ischemia-reperfusion injury (CIR-CA) following cardiopulmonary resuscitation (CPR). Here, we aimed to explore the role of pleiotrophin (PTN)/syndecan-3 pathway in heparin therapy for CIR-CA. MATERIALS AND METHODS: The CA-CPR model was constructed in Sprague-Dawley (SD) rats, which were treated with low molecular weight heparin, and the neurological changes and brain histopathological changes were evaluated. For in-vitro experiments, the ischemic injury model of primary neurons was established by oxygen and glucose deprivation (OGD), and the neuron regeneration was detected via the Cell counting Kit-8 (CCK8) method, flow cytometry and microscopy. CREB antagonist (KG-501), ERK antagonist (PD98059) and si-PTN were used respectively to inhibit the expression of CREB, ERK and PTN in cells, so as to explore the role of heparin in regulating neuronal regeneration. RESULTS: Compared with the sham rats, the neurological deficits and cerebral edema of CA-CPR rats were significantly improved after heparin treatment. Heparin also attenuated OGD-mediated neuronal apoptosis and promoted neurite outgrowth in vitro. Moreover, heparin attenuated CA-CPR-mediated neuronal apoptosis and microglial neuroinflammation. In terms of the mechanism, heparin upregulated the expression of ERK, CREB, NF200, BDNF, NGF, PTN and syndecan-3 in the rat brains. Inhibition of ERK, CREB and interference with PTN expression notably weakened the heparin-mediated neuroprotective effects and restrained the expression of ERK/CREB and PTN/syndecan-3 pathway. CONCLUSION: Heparin attenuates the secondary brain injury induced by CA-CPR through regulating the ERK/CREB-mediated PTN/syndecan-3 pathway.

Post-traumatic trigeminal neuropathy: correlation between objective and subjective assessments and a prediction model for neurosensory recovery.

BACKGROUND: Post-traumatic trigeminal neuropathy (PTN) can have a substantial effect on patient well-being. However, the relation between the neuropathic symptoms and their effect on psychosocial functioning remains a matter of debate. The purpose of this study was to evaluate the association between objective and subjective assessments of neurosensory function in PTN and predict neurosensory outcome using baseline measurements. METHODS: This prospective observational cohort study included patients diagnosed with PTN at the Department of Oral and Maxillofacial Surgery, University Hospital Leuven, Belgium, between April 2018 and May 2020. Standardized objective and subjective neurosensory examinations were recorded simultaneously on multiple occasions during the follow-up period. Correlation analyses and principal component analysis were conducted, and a prediction model of neurosensory recovery was developed. RESULTS: Quality of life correlated significantly (P < 0.05) with percentage of affected dermatome (ρ = - 0.35), the presence of brush stroke allodynia (ρ = - 0.24), gain-of-function sensory phenotype (ρ = - 0.41), Medical Research Council Scale (ρ = 0.36), and Sunderland classification (ρ = - 0.21). Quality of life was not significantly correlated (P > 0.05) with directional discrimination, stimulus localization, two-point discrimination, or sensory loss-of-function. The prediction model showed a negative predictive value for neurosensory recovery after 6 months of 87%. CONCLUSIONS: We found a strong correlation of subjective well-being with the presence of brush stroke allodynia, thermal and/or mechanical hyperesthesia, and the size of the neuropathic area. These results suggest that positive symptoms dominate the effect on affect. In patients reporting poor subjective well-being in the absence of positive symptoms or a large neuropathic area, additional attention towards psychosocial triggers might enhance treatment outcome. The prediction model could contribute to establishing realistic expectations about the likelihood of neurosensory recovery but remains to be validated in future studies.

In modern times, how important are breast cancer stage, grade and receptor subtype for survival: a population-based cohort study.

BACKGROUND: In breast cancer, immunohistochemistry (IHC) subtypes, together with grade and stage, are well-known independent predictors of breast cancer death. Given the immense changes in breast cancer treatment and survival over time, we used recent population-based data to test the combined influence of IHC subtypes, grade and stage on breast cancer death. METHODS: We identified 24,137 women with invasive breast cancer aged 20 to 74 between 2005 and 2015 in the database of the Cancer Registry of Norway. Kaplan-Meier curves, mortality rates and adjusted hazard ratios for breast cancer death were estimated by IHC subtypes, grade, tumour size and nodal status during 13 years of follow-up. RESULTS: Within all IHC subtypes, grade, tumour size and nodal status were independent predictors of breast cancer death. When combining all prognostic factors, the risk of death was 20- to 40-fold higher in the worst groups compared to the group with the smallest size, low grade and ER+PR+HER2- status. Among node-negative ER+HER2- tumours, larger size conferred a significantly increased breast cancer mortality. ER+PR-HER2- tumours of high grade and advanced stage showed particularly high breast cancer mortality similar to TNBC. When examining early versus late mortality, grade, size and nodal status explained most of the late (> 5 years) mortality among ER+ subtypes. CONCLUSIONS: There is a wide range of risks of dying from breast cancer, also across small breast tumours of low/intermediate grade, and among node-negative tumours. Thus, even with modern breast cancer treatment, stage, grade and molecular subtype (reflected by IHC subtypes) matter for prognosis.

RNA binding protein GNL3 up-regulates IL24 and PTN to promote the development of osteoarthritis.

Osteoarthritis (OA) is a degenerative disease, which has a high incidence in middle-aged and elderly people and tends to occur in weight-bearing or active joints. Current treatment can only relieve symptoms and delay the progression of OA in result of its indistinct pathogenesis. In recent years, more and more studies have focused on the pathogenesis of OA. Nucleolar GTP binding protein 3 (GNL3) is associated with chondrogenic differentiation and can participate in genomic regulation as RNA binding protein (RBP). We used RNA sequencing (RNA-seq) to analyze the overall transcription level of the human cervical cancer cell line HeLa after GNL3 deletion. The results showed that downstream genes IL24 and PTN were down-regulated. IL24 takes part in the progression of OA by inducing articular osteocyte apoptosis, while PTN conducts to the progression of OA by promoting angiogenesis. We validated the results in the human chondrosarcoma cell line SW1353 and OA patients. Compared with the control group, GNL3, IL24 and PTN genes were elevated in OA specimens. This study explored the relationship between GNL3 and these two downstream genes, hoping to find biomarkers in the pathogenesis of osteoarthritis that can be used as therapeutic targets in the future.

PTN-PTPRZ signalling is involved in deer antler stem cell regulation during tissue regeneration.

A growing deer antler contains a stem cell niche that can drive endochondral bone regeneration at up to 2 cm/day. Pleiotrophin (PTN), as a multifunctional growth factor, is found highly expressed at the messenger RNA level within the active antler stem cell tissues. This study aims to map the expression patterns of PTN protein and its receptors in a growing antler and investigate the effects of PTN on antler stem cells in vitro. Immunohistochemistry was employed to localise PTN/midkine (MDK) and their functional receptors, protein tyrosine phosphatase receptor type Z (PTPRZ), anaplastic lymphoma kinase (ALK), NOTCH2, and integrin αV ß3, on serial slides of the antler growth centre. PTN was found to be the dominantly expressed growth factor in the PTN/MDK family. High expression of PTPRZ and ALK co-localised with PTN was found suggesting a potential interaction. The high levels of PTN and PTPRZ reflected the antler stem cell activation status during the regenerative process. When antler stem cells were cultured in vitro under the normoxic condition, no PTN protein was detected and exogenous PTN did not induce differentiation or proliferation but rather stem cell maintenance. Collectively, the antler stem cell niche appears to upregulate PTN and PTPRZ in vivo, and PTN-PTPRZ signalling may be involved in regulating antler stem cell behaviour during rapid antler regeneration.

Up-regulation of miR-137 can inhibit PTN in target manner to regulate PTN/PTPRZ pathway to prevent cognitive dysfunction caused by propofol.

OBJECTIVE: To explore the effects of miR-137 on cognitive dysfunction in rats induced by propofol (PRO). METHODS: Male SD rats and SK-N-SH cells were purchased, and control and PRO groups were set up in the rats, and the same groups were set up in the cells. On the basis of the PRO group, miR-137 and PTN were up-regulated or down-regulated, and cognitive dysfunction and cell biological functions in each group were detected. RESULTS: The cognitive function of rats induced by PRO might be affected. We observed that the escape latency of PRO group was significantly prolonged, with significantly lower percentage of time for target platform exploration and times of crossing the platform, while over-expression of miR-137 or knock down of PTN could change the above results. Under PRO intervention, the expression of miR-137 in SK-N-SH cells decreased in a dose-dependent manner, while the expression and protein level of PTN in SK-N-SH cells increased in a dose-dependent manner. Cytotoxicity test yielded a 30 µM concentration of PRO as the optimal experimental concentration. When miR-137 and PTN were up-regulated or down-regulated, PRO-induced cell apoptosis, proliferation and PTN/PTPRZ pathway protein phosphorylation level were effectively reversed. Dual luciferase reporter confirmed that miR-137 and PTN have targeted relationship. CONCLUSION: Up-regulation of miR-137 can at least partially regulate PTN/PTPRZ pathway through the inhibition of PTN in a targeted manner, effectively inhibit cell apoptosis, and protect cognitive dysfunction caused by PRO.