Insulin-like growth factor-1 attenuates apoptosis and protects neurochemical phenotypes of dorsal root ganglion neurons with paclitaxel-induced neurotoxicity in vitro.

Paclitaxel (PT)-induced neurotoxicity is a significant problem associated with successful treatment of cancers. Insulin-like growth factor-1 (IGF-1) is a neurotrophic factor and plays an important role in promoting axonal growth from dorsal root ganglion (DRG) neurons. Whether IGF-1 has protective effects on neurite growth, cell viability, neuronal apoptosis and neuronal phenotypes in DRG neurons with PT-induced neurotoxicity is still unclear. In this study, primary cultured rat DRG neurons were used to assess the effects of IGF-1 on DRG neurons with PT-induced neurotoxicity. The results showed that PT exposure caused neurite retraction in a dose-dependent manner. PT exposure caused a decrease of cell viability and an increase in the ratio of apoptotic cells which could be reversed by IGF-1. The percentage of calcitonin gene-related peptide immunoreactive (CGRP-IR) neurons and neurofilament (NF)-200-IR neurons, mRNA, and protein levels of CGRP and NF-200 decreased significantly after treatment with PT. IGF-1 administration had protective effects on CGRP-IR neurons, but not on NF-200-IR neurons. Either extracellular signal-regulated protein kinase (ERK1/2) inhibitor PD98059 or phosphatidylinositol 3-kinase (PI3 K) inhibitor LY294002 blocked the effect of IGF-1. The results imply that IGF-1 may attenuate apoptosis to improve neuronal cell viability and promote neurite growth of DRG neurons with PT-induced neurotoxicity. Moreover, these results support an important neuroprotective role of exogenous IGF-1 on distinct subpopulations of DRG neurons which is responsible for skin sensation. The effects of IGF-1 might be through ERK1/2 or PI3 K/Akt signaling pathways. These findings provide experimental evidence for IGF-1 administration to alleviate neurotoxicity of distinct subpopulations of DRG neurons induced by PT.

Identification of 2 Potentially Relevant Gene Mutations Involved in Strabismus Using Whole-Exome Sequencing.

BACKGROUND The etiology of strabismus has a genetic component. Our study aimed to localize the candidate causative gene mutant in a Chinese family with strabismus and to describe its underlying etiology. MATERIAL AND METHODS Genomic DNA was extracted from the affected individual and his parents in a Chinese pedigree with strabismus. The resulting exomes were sequenced by whole-exome sequencing. After variant calling and filtering, the candidate causative gene mutations were selected for the rarity and predicted damaging effect, which complied with the model of recessive disease transmission. RESULTS We examined a Chinese strabismus pedigree with the parents unaffected and 2 offspring affected. Whole-exome sequencing and bioinformatics filtering identified 2 variants including Abelson helper integration site 1 (AHI1) gene and nebulin (NEB) gene. The variant in the AHI1 gene, c.A3257G (p.E1086G), and the altered amino acid had a damaging effect on the encoded protein predicted by Polyphen2. Moreover, this change was located in the conserved SH3 domain of AHI1. Biallelic pathogenic variant in AHI1 gene can cause Joubert syndrome-related disorders with oculomotor apraxia characteristics. Additionally, c.A914G mutation was found in nebulin (NEB) gene. Therefore, we concluded that AHI1 c.3257A>G and NEB c.914 A>G were potential causal variants in this strabismus pedigree. CONCLUSIONS We detected an AHI1 homozygous mutation in the affected individual. Whole-exome sequencing is a powerful way to identify causally relevant genes, improving the understanding of this disorder.

Neuregulin-1ß Regulates the migration of Different Neurochemical Phenotypic Neurons from Organotypically Cultured Dorsal Root Ganglion Explants.

Neuregulin-1ß (NRG-1ß) has multiple roles in the development and function in the nervous system and exhibits potent neuroprotective properties. In the present study, organotypically cultured dorsal root ganglion (DRG) explants were used to evaluate the effects of NRG-1ß on migration of two major phenotypic classes of DRG neurons. The signaling pathways involved in these effects were also determined. Organotypically cultured DRG explants were exposed to NRG-1ß (20 nmol/L), the phosphatidylinositol 3-kinase inhibitor LY294002 (10 µmol/L) plus NRG-1ß (20 nmol/L), the extracellular signal-regulated protein kinase (ERK1/2) inhibitor PD98059 (10 µmol/L) plus NRG-1ß (20 nmol/L), and LY294002 (10 µmol/L) plus PD98059 (10 µmol/L) plus NRG-1ß (20 nmol/L), respectively, for 3 days. The DRG explants were continuously exposed to culture media as a control. After that, all above cultures were processed for detecting the mRNA levels of calcitonin gene-related peptide (CGRP) and neurofilament-200 (NF-200) by real-time PCR analysis. CGRP and NF-200 expression in situ was determined by fluorescent labeling technique. The results showed that NRG-1ß elevated the mRNA and protein levels of CGRP and NF-200. NRG-1ß also increased the number and the percentage of CGRP-immunoreactive (IR) migrating neurons and NF-200-IR migrating neurons. Inhibitors (LY294002, PD98059) either alone or in combination blocked the effects of NRG-1ß. The contribution of NRG-1ß on modulating distinct neurochemical phenotypic plasticity of DRG neurons suggested that NRG-1ß signaling system might play an important role on the biological effects of primary sensory neurons.

In situ expression and serum level of thymic stromal lymphopoietin in oral lichen planus.

BACKGROUND: Oral lichen planus (OLP) is a chronic inflammatory disease of oral mucosa in which the CD8(+) T cell-mediated cytotoxicity is regarded as a major mechanism of pathogenesis. The main objective of this study is to investigate in situ expression and secretion of thymic stromal lymphopoietin (TSLP) in specimens and sera from patients with oral lichen planus. METHODS: Thirty-six patients with OLP and 35 donors enrolled in specimen and serum collection. Immunohistochemical method and immunofluorescence double-staining method were used to detect the expression of thymic stromal lymphopoietin and its receptor (TSLPR) together with CD8 in OLP specimens. Enzyme-linked immunosorbent assay (ELISA) was used to detect TSLP secretion. RESULTS: More TSLP- or TSLPR-positive cells showed in OLP specimens than in normal controls, and TSLP-positive cells were mainly in the epithelium, while TSLPR-positive cells mainly in the lamina propria. Furthermore, the number of TSLP-positive cells in the stratum basal was associated with the amount of mononuclear cells infiltrating in the lamina propria of OLP specimens. Among infiltrating mononuclear cells in the lamina propria, some CD8-positive cells also expressed TSLPR. The TSLP serum level of patients with OLP was significantly higher than of healthy donors, but there was no statistically difference between two clinical subtypes of OLP. CONCLUSIONS: Our findings provided the first evidence that TSLP may enroll in the pathology of OLP and the TSLP-TSLPR interaction may play an important role in it.

Rapamycin alleviates brain edema after focal cerebral ischemia reperfusion in rats.

Brain edema is a major consequence of cerebral ischemia reperfusion. However, few effective therapeutic options are available for retarding the brain edema progression after cerebral ischemia. Recently, rapamycin has been shown to produce neuroprotective effects in rats after cerebral ischemia reperfusion. Whether rapamycin could alleviate this brain edema injury is still unclear. In this study, the rat stroke model was induced by a 1-h left transient middle cerebral artery occlusion using an intraluminal filament, followed by 48 h of reperfusion. The effects of rapamycin (250 µg/kg body weight, intraperitoneal; i.p.) on brain edema progression were evaluated. The results showed that rapamycin treatment significantly reduced the infarct volume, the water content of the brain tissue and the Evans blue extravasation through the blood-brain barrier (BBB). Rapamycin treatment could improve histological appearance of the brain tissue, increased the capillary lumen space and maintain the integrity of BBB. Rapamycin also inhibited matrix metalloproteinase 9 (MMP9) and aquaporin 4 (AQP4) expression. These data imply that rapamycin could improve brain edema progression after reperfusion injury through maintaining BBB integrity and inhibiting MMP9 and AQP4 expression. The data of this study provide a new possible approach for improving brain edema after cerebral ischemia reperfusion by administration of rapamycin.

Capsaicin-induced activation of ERK1/2 and its involvement in GAP-43 expression and CGRP depletion in organotypically cultured DRG neurons.

Low concentrations of capsaicin (CAP) stimulate and high concentrations of CAP can be toxic to the primary sensory neurons of the dorsal root ganglion (DRG). CAP induces the phosphorylation of extracellular signal-regulated protein kinases 1/2 (ERK1/2) in DRG neurons. The effect of the activation of ERK1/2 by different concentrations of CAP on growth-associated protein 43 (GAP-43) expression and calcitonin gene-related peptide (CGRP) depletion in DRG neurons remains unknown. In the present study, organotypic embryonic 15-day-old rat DRG explants were used to determine the effect of different concentrations of CAP on GAP-43 expression and CGRP depletion. The results showed that, compared to unstimulated control cultures, GAP-43 and pERK1/2 protein levels increased at a low concentration (2 µmol/L) of CAP and decreased at a higher concentration (10 µmol/L). The number of CGRP-immunoreactive (IR) migrating neurons also decreased in CAP-treated cultures. The increase in GAP-43 levels and CGRP depletion could be blocked by the administration of ERK1/2 inhibitor PD98059. The results of the present study imply that CAP at different concentrations has different effects on GAP-43 expression and CGRP depletion. These effects were involved in the activation of ERK1/2 in organotypically cultured DRG neurons stimulated with CAP. These data may provide new insights for further development potential therapeutic applications of CAP with moderate dose on neurogenic inflammation.

Intensify Standardized Anticoagulation for Cancer-associated Pulmonary Embolism: From Single-center Real-world Data.

PURPOSE: Pulmonary embolism (PE) is a significant contributor to mortality in patients with cancer. Although anticoagulation serves as the cornerstone of treatment for cancer-associated PE, it has not been emphasized in real-world settings. The aim of this study was to examine the impact of suboptimal anticoagulant treatment on the prognosis of cancer-associated PE. METHODS: A cohort of 356 individuals newly diagnosed with acute PE were enrolled. The primary outcome of the study was recurrent venous thromboembolism (VTE), and the secondary outcomes were all-cause mortality and major bleeding (consisting of a reduction in the hemoglobin level by at least 20 g/L, transfusion of at least 2 units of blood, or symptomatic bleeding in a critical area or organ or fatal bleeding). FINDINGS: Of the total participants, 156 (43.8%) were diagnosed with cancer. A comparison between the cancer and noncancer groups revealed that patients with cancer were more frequently asymptomatic (41.0% vs 4.5%; P < 0.001), less likely to have right ventricular dysfunction (4.5% vs 14.0%; P = 0.001), received less anticoagulant treatment during hospitalization (85.3% vs 98.5%; P < 0.001), and had a shorter duration of anticoagulation (5.02 [7.40] months vs 14.19 [10.65] months; P < 0.001). In addition, patients with cancer were found to be at a higher risk of recurrent VTE (17.3% vs 4.0%; P < 0.001) and all-cause mortality (23.7% vs 10.5%; P = 0.001). Multiple Cox regression analysis indicated that discontinuation of anticoagulation at 3 months was a significant risk factor for recurrent VTE in the cancer group (HR, 15.815; 95% CI, 3.047-82.079; P = 0.001). IMPLICATIONS: The brief duration of anticoagulation therapy and elevated likelihood of recurrent VTE serve as cautionary indicators for the need to enhance awareness of standardized anticoagulant treatment for cancer-associated PE. The ultimate goal is to enhance patient prognosis and quality of life.

Pollinator sharing and hybridization in a pair of dioecious figs sheds light on the pathways to speciation.

The dynamics and processes underlying the codiversification of plant-pollinator interactions are of great interest to researchers of biodiversity and evolution. Cospeciation is generally considered a key process driving the diversity of figs and their pollinating wasps. Groups of closely related figs pollinated by separate wasps occur frequently and represent excellent opportunities to study ongoing diversification in this textbook mutualism. We study two closely related sympatric dioecious figs (Ficus heterostyla and Ficus squamosa) in Xishuangbanna, southwest China, and aim to document what is likely to be the final stages of speciation between these species using a combination of trait data and experimental manipulation. Volatile profiles at the receptive phase, crucial for attracting pollinators, were analyzed. In total, 37 and 29 volatile compounds were identified from receptive F. heterostyla and F. squamosa figs, respectively. Despite significant interspecific dissimilarity, 25 compounds were shared. Ovipositor lengths lie well within range required for access to heterospecific ovules, facilitating hybridization. Cross introduction of wasps into figs was conducted and hybrid seeds were generated for all donor/recipient combinations. F. heterostyla wasps produce adult offspring in F. squamosa figs. While F. squamosa wasps induce gall development in F. heterostyla figs and their offspring fail to mature in synchrony with their novel host. We record limited geographic barriers, minimal volatile dissimilarity, compatible morphology, complementary reproductive phenologies, and the production of hybrid seeds and wasp offspring. These findings suggest ongoing wasp specialization and reproductive isolation, potentially applicable to other related fig species.

Evaluation of bronchoscopic direct vision glottis anesthesia method in bronchoscopy.

BACKGROUND: Fibrobronchoscopy is a common adjunct tool that requires anesthesia and is widely used in the diagnosis and treatment of various respiratory diseases. However, current anesthesia methods, such as spray, nebulized inhalation, and cricothyroid membrane puncture, have their own advantages and disadvantages. Recently, studies have shown that bronchoscopic direct-view glottis anesthesia is a simple and inexpensive method that shortens the examination time and provides excellent anesthetic results. AIM: To evaluate the effectiveness of bronchoscopic direct vision glottis anesthesia for bronchoscopy. METHODS: The study included 100 patients who underwent bronchoscopy during thoracic surgery. A random number table method was used to divide the patients into control and observation groups (50 patients each). The control and observation groups were anesthetized using the nebulized inhalation and bronchoscopic direct vision glottis method, respectively. Hemodynamic indices [systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR), and oxygen saturation (SpO2) before (T1), 5 min after anesthesia (T2), and at the end of the operation (T3)] serum stress hormone indices [norepinephrine (NE), epinephrine (E), adrenocorticotropic hormone (ACTH), and cortisol (Cor) before and after treatment] were compared between the 2 groups. Adverse effects were also compared between the two groups. RESULTS: At T2 and T3, SBP, DBP, and HR were lower in the observation group than the control group, whereas SpO2 was higher than the control group [(119.05 ± 8.01) mmHg vs (127.05 ± 7.83) mmHg, (119.35 ± 6.66) mmHg vs (128.39 ± 6.56) mmHg, (84.68 ± 6.04) mmHg vs (92.42 ± 5.57) mmHg, (84.53 ± 4.97) mmHg compared to (92.57 ± 6.02) mmHg, (74.25 ± 5.18) beats/min compared to (88.32 ± 5.72) beats/min, (74.38 ± 5.31) beats/min compared to (88.42 ± 5.69) beats/min, (97.36 ± 2.21)% vs (94.35 ± 2.16)%, (97.42 ± 2.36)% vs (94.38 ± 2.69%], with statistically significant differences (all P < 0.05). After treatment, NE, E, ACTH, and Cor were significantly higher in both groups than before treatment, but were lower in the observation group than in the control group [(68.25 ± 8.87) ng/mL vs (93.35 ± 14.00) ng/mL, (53.59 ± 5.89) ng/mL vs (82.32 ± 10.70) ng/mL, (14.32 ± 1.58) pg/mL vs (20.35 ± 3.05) pg/mL, (227.35 ± 25.01) nmol/L vs (322.28 ± 45.12) nmol/L], with statistically significant differences (all P < 0.05). The incidence of adverse reactions was higher in the control group than in the observation group [12.00% (12/50) vs 6.00% (3/50)] (P < 0.05). CONCLUSION: The use of bronchoscopic direct vision glottis anesthesia method for bronchoscopy patients is beneficial for stabilizing hemodynamic indices during bronchoscopy and reducing the level of patient stress, with good safety and practicality.

Transforming growth factor-ß and bone morphogenetic protein signaling pathways in pathological cardiac hypertrophy.

Pathological cardiac hypertrophy (referred to as cardiac hypertrophy) is a maladaptive response of the heart to a variety of pathological stimuli, and cardiac hypertrophy is an independent risk factor for heart failure and sudden death. Currently, the treatments for cardiac hypertrophy are limited to improving symptoms and have little effect. Elucidation of the developmental process of cardiac hypertrophy at the molecular level and the identification of new targets for the treatment of cardiac hypertrophy are crucial. In this review, we summarize the research on multiple active substances related to the pathogenesis of cardiac hypertrophy and the signaling pathways involved and focus on the role of transforming growth factor-ß (TGF-ß) and bone morphogenetic protein (BMP) signaling in the development of cardiac hypertrophy and the identification of potential targets for molecular intervention. We aim to identify important signaling molecules with clinical value and hope to help promote the precise treatment of cardiac hypertrophy and thus improve patient outcomes.

[Clinical characteristics of in-hospital cardiac arrest in emergency patients in Kashgar area and analysis of influencing factors on success rate of cardiopulmonary resuscitation].

OBJECTIVE: To analyze the clinical characteristics of patients with emergency in-hospital cardiac arrest (IHCA) in Kashgar, Xinjiang Uygur Autonomous Region and the factors affecting the success rate of cardiopulmonary resuscitation. METHODS: Retrospectively selected patients who had cardiac arrest and cardiopulmonary resuscitation in the emergency department of the People's Hospital of 6 counties and cities in Kashgar area from January 2019 to January 2022. The clinical data of all patients were collected, including gender, age, major underlying diseases, the beginning and duration of resuscitation, the number of electric defibrillation acute physiology and chronic health evaluation II (APACHE II). According to whether the resuscitation was successful, all patients were divided into successful resuscitation group and failed resuscitation group. The clinical characteristics of the two groups were compared. Then, the influencing factors of the success rate of cardiopulmonary resuscitation in IHCA patients were analyzed by binary Logistic regression. RESULTS: A total of 1 376 patients were enrolled, including 1 117 cases of failed resuscitation and 259 cases of successful resuscitation. The success rate of resuscitation was 18.82%. Compared with the resuscitation failure group, the patients in the successful resuscitation group were younger (age: 49.10±20.99 vs. 58.44±18.32), the resuscitation start time was earlier [resuscitation start time ≤ 5 minutes: 76.45% (198/259) vs. 66.61% (744/1 117)], the proportion of cardiovascular and cerebrovascular diseases was lower [cardiovascular disease: 49.42% (128/259) vs. 58.19% (650/1 117), cerebrovascular disease: 17.37% (45/259) vs. 21.58% (241/1 117)], the number of electric defibrillation was lower [times: 0 (0, 2) vs. 1 (0, 1)], the proportion of endotracheal intubation was more [80.31% (208/259) vs. 55.60% (621/1 117)], APACHE II score was lower (13.75±8.03 vs. 17.90±4.63), and the difference was statistically significant (all P < 0.01). Binary Logistic regression analysis showed that age, start time of resuscitation, ventilation mode and APACHE II score were protective factors affecting the success rate of cardiopulmonary resuscitation in patients with emergency IHCA [age: odds ratio (OR) = 0.982, 95% confidence interval (95%CI) was 0.973-0.991, P < 0.001; resuscitation start time ≤ 5 minutes: OR = 0.629, 95%CI was 0.409-0.966, P = 0.034; tracheal intubation assisted ventilation: OR = 0.243, 95%CI was 0.149-0.397, P < 0.001; low APACHE II score: OR = 0.871, 95%CI was 0.836-0.907, P < 0.001], while underlying diseases (cardiovascular diseases) are a risk factor affecting the success rate of cardiopulmonary resuscitation (OR = 1.190, 95%CI was 1.015-1.395, P = 0.036). CONCLUSIONS: Age, resuscitation start time, ventilation mode, APACHE II score and major underlying diseases (cardiovascular diseases) have a greater impact on the success rate of resuscitation in IHCA patients. The above factors are conducive to improving or formulating more effective rescue strategies for IHCA patients, so as to achieve the purpose of improving the success rate of clinical treatment.

Expression of tyrosine kinase receptors in cultured dorsal root ganglion neurons in the presence of monosialoganglioside and skeletal muscle cells.

The neurotrophic factor-like activity of monosialoganglioside (GM1) has been shown to activate tyrosine kinase receptors (Trk). Targets of neuronal innervation play a vital role in regulating the survival and differentiation of innervating neurotrophin-responsive neurons. Both GM1 and target skeletal muscle (SKM) cells are essential for the maintenance of the function of neurons. However, much less is known about the effects of GM1 or/and target SKM cells on the expression of Trk receptors in dorsal root ganglion (DRG) neurons. Here we have tested what extent to the expression of TrkA, TrkB, and TrkC receptors in primary cultured of DRG neurons in absence or presence of GM1 or/and SKM cells. In this experiment, we found that: (1) GM1 promoted expression of TrkA and TrkB but not TrkC in primary cultured DRG neurons; (2) target SKM cells promoted expression of TrkC but not TrkA and TrkB in neuromuscular cocultures without GM1 treatment; and (3) GM1 and target SKM cells had additional effects on expression of these three Trk receptors. The results of the present study offered new clues for a better understanding of the association of GM1 and target SKM on the expression of Trk receptors.

[Study on the changes of fibronectin in the resected medial rectus of patients with concomitant exotropia].

OBJECTIVE: To study the changes of fibronectin in the resected medial rectus muscles in patients with concomitant exotropia and to have a better understanding about the pathomorphological changes of extraocular muscles in the genesis and development of concomitant exotropia. METHODS: Thirty-five concomitant exotropic patients were chosen as exotropic group and 20 normals were selected as control group. In the exotropic group, the age range 2 to 46 years old (mean, 20.9 ys), deviation range -45(Δ) to -90(Δ) (mean, -67.5(Δ)), 19 males, 16 females, and 8 cases have the family history. Exotropic patients were divided into intermittent exotropic group 16 cases and constant exotropic group 19 cases. In the control group, the age range 15 - 28 years old (mean, 18.8 years), 12 males and 8 females. All the resected tissues of the medial rectus muscles were obtained from patients with concomitant exotropia during resection surgery and cornea donators. Fibronectin was measured its mean average optical by Sp method of immunohistochemistry using image analyzer. The amounts of fibronectin in the resected muscle of patients were compared with normals, as well as correlated clinical data of patients such as different types of exotropia, age, degree of deviation, gender and positive family history. RESULTS: The amounts of fibronectin in the resected medial rectus muscle of patients with constant exotropia (0.4729 ± 0.0872) were significantly lower than those of normals (0.5914 ± 0.0547) and intermittent exotropic group (0.5821 ± 0.0792) respectively (q = 7.0314, 6.1177, P < 0.01), while patients with intermittent exotropia did not show significantly lower amounts of fibronectin than those with normals (q = 0.5271, P > 0.05). Neither gender nor positive family was correlated with the amounts of fibronectin (t = 1.1317, 1.6327, P > 0.05) and the amounts of fibronectin had no correlation with age and degree of deviation. CONCLUSION: The amounts of fibronectin were correlated with the course of development of concomitant exotropia. Some of these changes may play a role in the pathogenesis of exotropia from intermittence to constancy, which indicates a further clue to the nature of this disease.

Inhibitory role of puerarin on the A549 lung cancer cell line.

Background: Although more and more drugs had been proved to be effective in controlling tumor cells, lung cancer was still the leading cause of cancer-related deaths all over the world. This study aimed to investigate the effect and mechanism of puerarin on the invasion and metastasis of A549 lung cancer cell line. Methods: A medium containing puerarin was prepared according to the gradient concentration, and 10, 20, and 40 µmol/L were selected as the experimental group (low, medium, and high concentration groups, respectively) according to the cytotoxicity experiment. Meanwhile, 0 µmol/L was used as the control group. Results: Following administration, metastasis-related indexes were detected by the cell scratch test, cell migration test, gene difference detection, and western blotting. 24 hours after administration, the cell scratch and Transwell showed that the migration ability of A549 cells decreased with the increasing puerarin concentration. The polymerase chain reaction (PCR) and western blotting results demonstrated that the expression of the cell invasion and metastasis-related factor, matrix metallopeptidase 9 (MMP9), was negatively correlated with drug concentration. Further investigation demonstrated that the phosphorylation of extracellular signal-regulated kinase (ERK) was also inhibited. Conclusions: Puerarin can inhibit the expression of invasion and metastasis-related factors by inhibiting the phosphorylation of ERK.

OPN promotes survival of activated T cells by up-regulating CD44 in patients with oral lichen planus.

Oral lichen planus (OLP) is a chronic inflammatory disorder of oral mucosa, which represents cell-mediated autoimmune diseases. Pathological study demonstrated that abundant T lymphocytes infiltrated the oral mucosa, in which the activated T cells that trigger apoptosis of oral epithelial cells is an important mechanism for OLP. However, to date the molecular mechanisms underlying the T lymphocytes infiltration and accumulation in OLP remain unclear. In this paper, we found that the levels of plasma OPN were elevated and were associated with the up-regulated expressions of CD44 in OLP patients. In vitro, the addition of exogenous OPN can suppress the apoptosis of activated CD8(+) T cells via CD44, and this T cell resistance to apoptosis may be attributed to the reduction of endogenous mature granzyme B. Our results suggested that the abnormally elevated levels of OPN may contribute to the abnormal infiltration and accumulation of the activated T cells by up-regulating CD44 in OLP.

The possible roles of OPN-regulated CEACAM1 expression in promoting the survival of activated T cells and the apoptosis of oral keratinocytes in oral lichen planus patients.

Oral lichen planus is a chronic inflammatory disorder of the oral mucosa that represents T cell-mediated autoimmune diseases. The regulation and roles of carcinoembryonic antigen-related cellular adhesion molecule 1 (CEACAM1), a novel immune molecule, in the immunopathogenesis of T cell-mediated autoimmune diseases remain unclear. In the current paper, CEACAM1 was found to be overexpressed in peripheral T cells and epithelial cells in oral lichen planus patients. A fraction of infiltrating inflammatory mononuclear cells in the lamina propria of the oral lichen planus mucosa also expressed CEACAM1. Importantly, for the first time, CEACAM1 expression in T cells and in normal human oral keratinocytes was demonstrated to be regulated differently by osteopontin in vitro. Furthermore, the apoptosis of oral keratinocytes and activated T cells can be markedly suppressed by CEACAM1-specific monoclonal antibodies. In conclusion, OPN-regulated CEACAM1 expression may play a critical role in the immunopathogenesis of oral lichen planus.

Differential expression of proteins in monozygotic twins with discordance of infantile esotropic phenotypes.

PURPOSE: To identify strabismus-related proteins, we performed proteome analysis in monozygotic twins with discordance of congenital esotropic phenotypes and in normal children. METHODS: Surface-enhanced laser desorption/ ionization time-of-flight mass spectrometry (SELDI-TOF-MS) technology was used to detect changes in protein expression in a pair of twins with discordant esotropic phenotypes (twin A is orthotropic and twin B is esotropic). In addition, two non-twin esotropic children and two orthotropic children of the same age were chosen. The differentially expressed proteome obtained was validated in twelve non-twin esotropic children and eighteen orthotropic children and compared to the protein database. RESULTS: We detected four differentially expressed proteins in monozygotic twins with discordance of congenital esotropic phenotypes. The corresponding molecular weights were 4,146 Da, 4,801 Da, 7,786 Da, and 5,859 Da, respectively. Among these 4 proteins, the first three proteins were down-regulated and the last was upregulated. The initial characterization of these detected proteins via protein library revealed that their characteristics were similar to those of the glucagon precursor, pituitary adenylate cyclase-activating polypeptide (PACAP), camp-dependent protein kinase inhibitor α, and anti-metastasis gene (antigen), respectively. CONCLUSIONS: There were differentially expressed proteins between monozygotic twins with discordance of congenital esotropic phenotypes and normal children. These differentially expressed proteins were mainly down-regulated in the strabismus patients and may be involved in the occurrence and development of congenital esotropia.

Over-expression of Gadd45a enhances radiotherapy efficacy in human Tca8113 cell line.

AIM: To investigate the effect of the growth arrest- and DNA damage-inducible Gadd45a gene on the radiosensitivity of human tongue squamous cell carcinoma cell line to ionizing radiation (IR). METHODS: Short interfering ribonucleic acid (si-RNA) targeting Gadd45a or an irrelevant mRNA (nonsense si-RNA) was chemically synthesized. The constructed si-RNAs were transfected into Tca8113 cells and Gadd45a expression was determined using quantitative real-time PCR and Western-blot. After 24-h exposure to IR at a dose rate of 4 Gy/min, apoptosis of Tca8113 cells was detected using flow cytometry, and radiosensitivity was measured using MTT assays. RESULTS: IR apparently increased the expression of Gadd45a at mRNA and protein levels in Tca8113 cells. The effect was efficiently inhibited by transfection with Gadd45a si-RNA (P<0.01). Furthermore, silencing Gadd45a gene significantly increased cell viability and decreased the percentage of apoptotic cells during irradiation, which indicated that IR-induced Gadd45a over-expression could increase the radiosensitivity of Tca8113 cells. CONCLUSION: These results indicated that targeting Gadd45a may have important therapeutic implications in sensitizing Tca8113 cells to IR.

The protective effects of calcitonin gene-related peptide on gastric mucosa injury of gastric ischemia reperfusion in rats.

Gastric mucosa is one of the most vulnerable tissues in human and animal. However, little is known about the effects of calcitonin gene-related peptide (CGRP) on gastric mucosa injuries induced by gastric ischemia reperfusion. The purpose of the present study was to investigate the protective effects and mechanism of CGRP on gastric mucosa injury after gastric ischemia reperfusion in rats. Thirty-six healthy Wistar rats were randomly divided into CGRP-treated, sham-operated, and control groups. Twelve rats were involved in each group. These groups were further divided into 24-h and 48-h subgroups. Gastric ischemia reperfusion injury (GI-RI) rat model was established by a 30-min celiac artery occlusion by an artery clamp, followed by 24 h or 48 h of reperfusion. CGRP (1 µg/ml) at the dose of 3 µg/kg was given intraperiloneally (IP) at the beginning of reperfusion for rats in CGRP-treated group. Saline as vehicle (3 ml/kg body weight), IP, was administered at the beginning of reperfusion for rats in control group. Sham-operated animals were subjected to an operation without GI-RI. Twenty-four hours or 48 h after operation, the samples were taken out and processed for calculating stomach mucous membrane damage index according to Guth method, detecting pathological changes of gastric mucosa tissue by light microscopy and observing the expression of gastrin (Gas) and somatostatin (SST) by immunohistochemical staining. The results showed the following: (i) gastric mucosa with diffuse edema, splinter hemorrhage and erosion, numerous endothelial cells necrosis, mucosa dissociation, and infiltration of inflammatory cells were observed in both control and CGRP-treated animals, especially in the earlier period (24 h) and then gradually healing. CGRP administration could reduce the damage of gastric mucosa. The injury index of gastric mucosa was lower in CGRP-treated group as compared with that in control group (P < 0.01). (ii) Gas expression in gastric antrum mucosa was lower in CGRP-treated group than that in control group (P < 0.01). SST expression in gastric antrum mucosa was higher in CGRP-treated group than that in control group (P < 0.01). It is concluded that CGRP regulated the secretion of Gas and SST and thus alleviated the damage of gastric mucosa induced by ischemia and reperfusion. CGRP might be a potential candidate for clinical therapy on modulating gastric mucosal protection and maintaining gastric mucosal integrity after ischemia and reperfusion of the stomach.

MXene Enabling the Long-Term Superior Thermo-Oxidative Resistance for Elastomers.

The ability of long-term thermo-oxidative resistance is very important for elastomers in application. However, many conventional antioxidants are difficult to realize the long-term thermo-oxidative resistance. To overcome this limitation, a design strategy is introduced by combing elastomers with MXene and natural rubber (NR) is chosen as a model material. MXene is efficient in absorbing oxygen and the generated free radicals in the NR matrix and can inhibit the diffusion of oxygen toward the interior. Moreover, MXene, like graphene and carbon black, absorbs molecular chains, inhibiting the migration of MXene toward the surface of the sample. Such characteristics of MXene endow NR/MXene with the long-term outstanding thermo-oxidative resistance. For example, after three days of the thermo-oxidative process for NR/MXene, the tensile strength is 19 MPa and the retention of tensile strength is 63%, which far exceeds the effects of conventional antioxidants. This work not only provides a good guide for the universal design of elastomers with long-term thermo-oxidative resistance but also expands the application of MXene.