Analysis of cuproptosis-related lncRNA signature for predicting prognosis and tumor immune microenvironment in pancreatic cancer.

Pancreatic cancer (PC) is a highly malignant digestive tract tumor, with a dismal 5-year survival rate. Recently, cuproptosis was found to be copper-dependent cell death. This work aims to establish a cuproptosis-related lncRNA signature which could predict the prognosis of PC patients and help clinical decision-making. Firstly, cuproptosis-related lncRNAs were identified in the TCGA-PAAD database. Next, a cuproptosis-related lncRNA signature based on five lncRNAs was established. Besides, the ICGC cohort and our samples from 30 PC patients served as external validation groups to verify the predictive power of the risk signature. Then, the expression of CASC8 was verified in PC samples, scRNA-seq dataset CRA001160, and PC cell lines. The correlation between CASC8 and cuproptosis-related genes was validated by Real-Time PCR. Additionally, the roles of CASC8 in PC progression and immune microenvironment characterization were explored by loss-of-function assay. As showed in the results, the prognosis of patients with higher risk scores was prominently worse than that with lower risk scores. Real-Time PCR and single cell analysis suggested that CASC8 was highly expressed in pancreatic cancer and related to cuproptosis. Additionally, gene inhibition of CASC8 impacted the proliferation, apoptosis and migration of PC cells. Furthermore, CASC8 was demonstrated to impact the expression of CD274 and several chemokines, and serve as a key indicator in tumor immune microenvironment characterization. In conclusion, the cuproptosis-related lncRNA signature could provide valuable indications for the prognosis of PC patients, and CASC8 was a candidate biomarker for not only predicting the progression of PC patients but also their antitumor immune responses.

ADAMTS12 promotes migration and epithelial-mesenchymal transition and predicts poor prognosis for pancreatic cancer.

BACKGROUND: ADAMTS (a disintegrin and metalloproteinase with thrombospondin-like motifs) family, a group of extracellular multifunctional enzymes, has been proven to play a pivotal role in the tumor. In pancreatic cancer, the role and mechanism of this family remain unclear. The present study aimed to figure out the hub gene of ADAMTSs and explore the exact roles in the prognosis and biological functions in pancreatic ductal adenocarcinoma (PDAC). METHODS: We used several databases to analyze the ADAMTS family and then screen out the hub genes. The expression of ADAMTS12 in 106 pairs of PDAC tumors and adjacent normal tissues was examined by immunohistochemistry, and its correlations with clinical parameters were further analyzed. The impacts of ADAMTS12 on the migration of PDAC cells were predicted by gene set enrichment analysis and confirmed by transwell assays. The potential impacts of ADAMTS12 on the epithelial-mesenchymal transition (EMT) were identified by database analysis and experimental proof of real-time quantitative polymerase chain reaction (qPCR) and Western blotting. RESULTS: Our study found that ADAMTS12 was a crucial gene in PDAC, and it was highly expressed in tumor tissues when compared to that in the adjacent tissues. ADATMS12 had predictive value of a poor prognosis for PDAC. The elevation of ADAMTS12 was parallel to the progression of PDAC. Inhibition of ADAMTS12 suppressed the migration of PDAC cells and interfered with the process of EMT. CONCLUSIONS: ADAMTS12 is a crucial member of ADAMTSs in PDAC and a predictor of poor prognosis. Additionally, based on its impacts on migration and metastasis in PDAC and the relationship with EMT, ADAMTS12 plays a role of an oncogene in PDAC and may be a promising target for treatment.

A Study on Environmental Factors for Nonsyndromic Cleft Lip and/or Palate.

The aim of the study was to investigate the association between environmental factors and nonsyndromic cleft of the lip and/or palate (NSCL/P) in Yantai District, China. A retrospective case-control study was carried out. A total of 236 NSCL/P children were selected from Department of Oral and Maxillofacial Surgery of Yantai Stomatological Hospital between September 2013 and December 2016 as cases; 209 controls were chosen from other diagnosis in the same department during the same period. The 2 groups matched age and sex. The parents of participants were inquired regarding the risk factors, and the answers were filled in a questionnaire by physicians. Chi-square and multivariate logistic regression analysis were used to analysis the data. There was significantly increased NSCL/P risk with high maternal age (P =0.002), family history (P = 0.001), abortion history (P = 0.033), poor parental education level (P = 0.008), maternal smoking (P = 0.044), maternal alcohol (P = 0.039), common cold or fever (P = 0.035), drug use (P = 0.006), and maternal stress (P = 0.049). Reduced NSCL/P risk was found with folic acid supplementation (P = 0.005), adequate maternal age (P = 0.002), and high parental education (P = 0.001). The proper amount of folic acid, the appropriate age of childbearing, and the high education were the protective factors of NSCL/P, whereas family history, abortion history, drug use during pregnancy, maternal tobacco and alcohol, and maternal stress were the risk factors for NSCL/P in Yantai District, China.

Clinical Outcomes of Infants With Periorbital Hemangiomas Treated With Oral Propranolol.

PURPOSE: Periorbital infantile hemangiomas (IHs) require early intervention because they have the potential risk of causing visual disturbances. In recent years, propranolol has shown promise in the effective management of periocular and periorbital IHs. The objective of our study was to assess the clinical outcomes, efficacy, and safety of propranolol in the management of infants with high-risk periorbital IHs. PATIENTS AND METHODS: This retrospective study was conducted at the Stomatological Hospital affiliated with China Medical University. The medical records of infants with periorbital hemangiomas who were treated with systemic propranolol at a dose of 1.0 to 1.5 mg/kg per day between January 2014 and June 2015 were reviewed. We excluded infants who did not qualify for propranolol treatment and infants who received previous therapy or other treatments. The records were reviewed for treatment response, adverse events during treatment, length of treatment, and recurrences. Treatment response was classified using a 4-point scale system based on reduction in volume as poor (<25%), moderate (25 to 50%), good (50 to 75%), or excellent (>75 to 100%) and change in color, as well as surface texture, by a panel of 3 plastic surgeons using 2-dimensional photographs, clinical examination, and Doppler ultrasonography measurements taken before and after treatment. RESULTS: Of 38 infants with periorbital hemangiomas, 26 were treated with systemic propranolol at a dose of 1.0 to 1.5 mg/kg administered once daily. A total of 11 male and 15 female infants with a mean age of 5.2 months (range, 2 to 12 months) were treated. The mean length of treatment was 22 weeks (range, 4 to 41 weeks). Adverse events of diarrhea (n = 3) and sleep changes (n = 1) were encountered during treatment in 4 patients. The overall treatment response was scored as excellent in 17 patients, good in 7, moderate in 2, and poor in 0. No patients required discontinuation of treatment because of adverse events, and there were no cases of recurrence or tumor regrowth noted during the mean follow-up period of 6.5 months (range, 3 to 10 months). CONCLUSIONS: Oral propranolol at a dose of 1.0 to 1.5 mg/kg per day (age ≤3 months, 1.0 mg/kg; age >3 months, 1.5 mg/kg) was effective and well tolerated for the management of 26 Chinese infants with high-risk periorbital IHs. Early intervention should be considered to reduce risk of visual impairment and improve esthetic outcomes.

Oral Propranolol for the Treatment of Infantile Hemangiomas in the Post-Proliferative Phase: A-Single Center Retrospective Study of 31 Cases.

PURPOSE: Infantile hemangiomas (IHs) are the most common benign tumors affecting infants, and most IHs are self-limiting. However, there are cases that require specific treatment. Propranolol is now widely used to treat severe IHs. Several studies have shown the efficacy and limited side effects associated with propranolol as the first-line treatment for IHs. There are a limited number of publications describing the role of propranolol in treating IHs beyond the proliferative phase (>12 months). The purpose of this study was to evaluate the effects and safety of oral high-dose (2.0 mg/kg per day) propranolol for IHs beyond the proliferative phase (>12 months). PATIENTS AND METHODS: This study enrolled patients with IHs who accepted systemic propranolol treatment from the Department of Oral and Maxillofacial Surgery, Stomatological Hospital Affiliated China Medical University. This is a single-center retrospective study conducted from April 2011 to July 2015. All children who were older than 12 months were eligible for the study. Digital photographs taken before and after treatment were analyzed by a panel of 3 plastic surgeons. The esthetic results were evaluated using a 4-point scale and ranked as poor, moderate, good, or excellent. The patient follow-up visits were scheduled monthly, and changes in the size, texture, and color of the lesions were recorded. The adverse effects after medication were evaluated and managed accordingly. RESULTS: We collected data on 31 eligible patients. The 31 patients had 32 hemangiomas (1 female patient had 2 lesions) and were treated with systemic propranolol at a high dose of 2 mg/kg per day. The mean age at the initiation of propranolol therapy was 18.4 months (range, 12 to 48 months), and the mean treatment duration was 10.1 months (range, 8 to 16 months). The treatment responses for the 32 hemangiomas included 17 excellent responses (53.1%), 8 good responses (25%), and 7 moderate responses (21.9%). There were no severe side effects encountered and recurrence was observed in 3 patients during the treatment and follow-up course. CONCLUSIONS: Oral propranolol, 2 mg/kg per day, is a safe and effective treatment for IHs beyond the proliferative phase (>12 months of age) in the Chinese population.

Synthesis of the New-Type Vascular Endothelial Growth Factor-Silk Fibroin-Chitosan Three-Dimensional Scaffolds for Bone Tissue Engineering and In Vitro Evaluation.

The objective of the study was to discuss the biocompatibility of the vascular endothelial growth factor-silk fibroin-chitosan (VEGF-SF-CS) scaffolds. To offer an ideal scaffold for bone tissue engineering, the author added vascular endothelial growth factor (VEGF) into silk fibroin-chitosan (SF-CS) scaffold directly to reconstruct a three-dimensional scaffold for the first time, SF-CS scaffold was loaded with VEGF and evaluated as a growth factor-delivery device. Human fetal osteoblast cell was seeded on the VEGF-SF-CS scaffolds and SF-CS scaffolds. On VEGF-SF-CS and SF-CS scaffolds, the cell adhesion rate was increased as time went on. Scanning electron microscopy: the cells grew actively and had normal multiple fissions, granular and filamentous substrates could be seen around the cells, and cell microfilaments were closely connected with the scaffolds. The cells could not only show the attached growth on surfaces of the scaffolds, but also extend into the scaffolds. Cell Counting Kit-8 and alkaline phosphatase analysis proved that the VEGF could significantly promote human fetal osteoblast1.19 cells growth and proliferation in the SF-CS scaffolds, but the enhancement of osteoblasts cell proliferation and activity by VEGF was dependent on time.

Oral Propranolol With Topical Timolol Maleate Therapy for Mixed Infantile Hemangiomas in Oral and Maxillofacial Regions.

PURPOSE: The combination treatment for mix infantile hemangiomas (IHs) using oral propranolol with topical timolol maleate was not well documented in the literature. The aim of this study was to evaluate the therapeutic effects and safety of oral propranolol along with topical timolol maleate or oral propranolol alone for treating mixed IHs in the oral and maxillofacial regions. METHODS: Between March 2013 and June 2014, a total of 31 patients with mixed IHs in the oral and maxillofacial regions were recruited to the study and randomly divided into experimental and control groups. Fourteen patients in the experimental group (A) were treated with oral proranolol in combination with topical timolol maleate, and 17 patients in the control group (B) underwent orally proranolol treatment alone. The maximal treatment duration was planned for 8 months. Ultrasonography and serial photographs based on Visual Analogue Scale (VAS) were used to assess the effects of treatment before and after treatment, as well as adverse effects after medication were evaluated and managed accordingly. RESULTS: All patients completed treatment. Among the most patients, there was obvious fading of color or decrease in size of the IHs when compared with pretreatment. There was significant reduction of color fading in A (mean VAS score: 8.36 ± 1.39) than that in B (7.18 ± 1.71) (P = 0.043) after the end of treatment, whereas the reduction of sizes in A (8.00 ± 1.75) had no significant difference than that in B (7.59 ± 1.80) (P= .51). The treatment duration of A (5.64 ± 1.45) was shorter than that of B (6.71 ± 1.10) (P= .037). No major collateral effects were observed in both the groups throughout the course of treatment. CONCLUSIONS: Oral proranolol combined with topical timolol maleate was well tolerated and effective treatment, mild side effects, and especially gave rise to better clinical response in the treatment of mixed IHs than oral propranolol alone.

Percutaneous Treatment of Large Venous Malformations in the Oral and Maxillofacial Regions Using Electrochemical Therapy Combined With Pingyangmycin.

PURPOSE: The aim of the present study was to evaluate the therapeutic outcome of using electrochemical therapy (ECT) combined with a sclerosing agent, pingyangmycin (bleomycin A5 hydrochloride; PYM), for large (>3 cm in diameter) venous malformations (VMs) in the oral and maxillofacial regions. PATIENTS AND METHODS: Thirty-five patients (15 male and 20 female; age range, 10 to 69 yr; mean age, 32 yr) with large VMs in the oral and maxillofacial region were treated with a combination of ECT and PYM under general anesthesia in the authors' department from June 2012 through May 2014. The size of the lesions varied from 3 × 3 to 12 × 15 cm. A repeated course of ECT and PYM was administered for larger VMs. The therapeutic interval was 3 months for ECT and 2 to 4 weeks for PYM. The dose of PYM for patients was 8 mg each time, and the injection concentration of PYM was 1.6 mg/mL. Patients were followed for 6 to 36 months. Therapeutic results were evaluated by clinical examination and Doppler ultrasonography before and after treatment. RESULTS: Of the 35 patients, 29 (82.9%) received 1 ECT treatment, 5 (14.3%) received 2 ECT treatments, and 1 (2.8%) received 3 ECT treatments. The number of PYM injection sessions was 1 to 5 (average, 2.5 times). According to the therapeutic criteria, the clinical outcome was excellent in 22 patients (62.9%), good in 10 patients (28.6%), and fair in 3 patients (8.5%). All patients (100%) had local swelling postoperatively that lasted approximately 1 to 2 weeks. Two patients (5.7%) had fever. No skin necrosis or nerve damage was found. CONCLUSIONS: Percutaneous treatment using ECT and PYM was a straightforward, safe, and reliable treatment modality for large VMs.

Topical timolol maleate for superficial infantile hemangiomas: an observational study.

PURPOSE: The objective of this study was to assess the clinical effects and safety of topical timolol maleate for the management of superficial infantile hemangiomas (IHs). MATERIALS AND METHODS: From October 2012 to March 2014, 35 infants (24 girls and 11 boys; 2 to 10 months old; median age, 4.7 months) with superficial hemangiomas were treated with the local application of timolol maleate in the authors' department. Thirty-five lesions were treated using topically administrated timolol maleate every 12 hours for a mean duration of 22 weeks (range, 6 to 45 weeks). Follow-up visits were scheduled monthly and changes in tumor size, texture, and color were recorded. Treatment response was scored according to a 3-point scale system as good, partial, or no response. Adverse effects after medication were evaluated and managed accordingly. RESULTS: All patients completed treatment. Of the 35 hemangiomas, 18 (51.4%) showed a good response, 10 (31.4%) showed a partial response, and 6 (17.2%) had no response. The total response rate was 82.8% (29 of 35). Clinically, no systemic or local side effects caused by timolol maleate were observed in the patients. CONCLUSIONS: Topical timolol maleate could provide an effective and safe alternative to the systemic use of propranolol for the treatment of superficial IHs. Further prospective studies are needed to confirm the efficacy and safety of topical timolol maleate for the treatment of IHs.

Treatment of severe infantile hemangiomas with propranolol: an evaluation of the efficacy and effects of cardiovascular parameters in 25 consecutive patients.

PURPOSE: The aim of this study was to investigate the therapeutic results and effects of propranolol on cardiovascular parameters in infants receiving systemic propranolol for complicated infantile hemangiomas (IHs), as well as to evaluate the adverse effects of propranolol throughout the course of treatment. MATERIALS AND METHODS: Twenty-five consecutive patients who presented with complicated IHs were prospectively recruited into this study between April 2012 and June 2013. All patients were treated with systemic propranolol at a dose of 1.0 to 1.5 mg/kg, and the drug was taken once per day. The length of treatment was 8.2 months on average and ranged from 6 to 12 months. The follow-up visits were scheduled monthly after discharge. Changes were recorded during the 3-day hospitalization, including systolic and diastolic blood pressures, heart rate, and blood glucose level. The treatment responses were scored according to a 4-point scale system as very good, good, mild, or no response. The adverse effects after medication administration were evaluated and managed accordingly. RESULTS: Of the 25 patients, 8 (32%) had a very good response, 11 (44%) had a good response, and 6 (24%) had a mild response. When pretreatment and post-treatment values were compared, there was no significant decrease in mean systolic and diastolic blood pressures and mean heart rate (all P > .05). The decreases in the cardiovascular parameters were not commonly associated with observable clinical symptoms. No major collateral effects were observed, and no infants were withdrawn from treatment because of side effects. CONCLUSIONS: Fluctuations from the normal ranges of cardiovascular parameters occurred frequently with the initiation of propranolol, but were clinically asymptomatic. Therefore oral propranolol was an effective and safe treatment for IHs, particularly for early intervention suitable for severe IHs.

The Effect of Tumor Necrosis Factor-α at Different Concentrations on Osteogenetic Differentiation of Bone Marrow Mesenchymal Stem Cells.

Tumor necrosis factor-alpha (TNF-α) has been demonstrated to have a close relationship with inflammation in the body. Although most researchers confirmed that TNF-α can have an effect on the expression of osteoblast specific genes, they had not elucidated the regulation of inflammatory factors in osteogenic gene expression during the process of bone marrow mesenchymal stem cells (BMMSCs) differentiating to osteoblast. The aim of this study was to investigate the effect of TNF-α at different concentrations on osteogenetic differentiation of BMMSCs. In this study, BMMSCs proliferation was analyzed by using cell counting kit-8 assay, cell osteogenic differentiation was evaluated by means of alkaline phosphatase activity assay and Von Koaas staining and the messenger RNA (mRNA) expression of bone morphogenetic proteins-2 (BMP-2) and drosophila mothers against decapentaplegic protein 1 (Smad1) was measured through real-time polymerase chain reaction. The results indicated that a low concentration of TNF-α at short-term promotes the osteogenetic differentiation of BMMSCs and increases the mRNA expression of BMP-2 and Smad1, but inhibits the osteogenetic differentiation of BMMSCs and the expression of BMP-2 and Smad1 at long term. In addition, regardless of a short or long time, a high concentration of TNF-α inhibits the osteogenetic differentiation of BMMSCs and the expression of Smad1, but results in a high expression of BMP-2.

Mattress cerclage combined with electrochemical therapy and pingyangmycin injection after embolization for management of arteriovenous malformation on oral and maxillofacial region.

BACKGROUND: The purpose of the article was to assess the clinical results of mattress cerclage combined with electrochemical therapy and pingyangmycin injection after embolization in treating arteriovenous malformations (AVMs). METHODS: During the period from January 2008 to December 2012, a total of 26 patients with AVMs were treated through mattress cerclage combined with electrochemical therapy and pingyangmycin injection after embolization and were retrospectively examined. The size of the lesions ranged from 2.5 cm × 3 cm to 8 cm × 10 cm. The follow-up time varied from 8 months to 24 months. The clinical outcome was evaluated using a 4-grade scale. RESULTS: All the lesions decreased in size after the treatment. The clinical follow-up showed excellent response in 20 of the 26 patients, whereas the remaining 6 patients also had satisfactory response. The most common complication was swelling, followed by pain and fever, without serious adverse effects being encountered. CONCLUSIONS: Mattress cerclage combined with electrochemical therapy and pingyangmycin injection after embolization was a reliable method for AVMs.

Oral propranolol for parotid infantile hemangiomas.

The aim of our study was to assess the efficacy and safety of oral propranolol for the treatment of parotid infantile hemangiomas. Between October 2009 and January 2013, propranolol was given orally to 30 infants with proliferating hemangiomas at a dose of 1.0 to 1.5 mg/kg per day in our department. The patients included 12 male infants and 18 female infants, aged between 2 and 13 months, with a median of 5.9 months. The lesions were located in the parotid region and measured from 1.5 cm × 2 cm × 0.5 cm to 6 cm × 8 cm × 3 cm in volume. Oral propranolol was administered once daily for a mean duration of 22.7 weeks (range, 14-32 wk). Follow-up times were from 1 to 10 months (median, 6.4 mo). Changes in the color and size of the tumor were recorded using hemisphere measurements and digital photographs. The treatment results were scored according to a 4-point scale. Overall response was graded scale 4 (excellent) in 18 patients, scale 3 (good) in 11 patients, scale 2 (moderate) in 1 patient, and scale 1 (poor) in none. No major collateral effects and rebounds were observed in any of the patients. Oral propranolol was a well-tolerated and effective treatment with mild adverse effects for parotid infantile hemangiomas.

Appraisal of efficacy and safety of intralesional injection of high concentration of bleomycin A5 for treatment of huge macrocystic lymphatic malformations in cervical region.

The objective of this study was to investigate the therapeutic effects and safety of intralesional injection of high concentration of bleomycin A5 for huge (more than 5 cm in diameter) macrocystic lymphatic malformations (LMs) in the cervical region. Thirty-two patients with huge macrocystic LMs were treated with percutaneous injection of bleomycin A5 in our department between 2006 and 2011. Among them, 13 patients had unilateral submandibular lesions, and 19 patients had lesions in anterior cervical regions. The age of patients ranged from 10 months to 29 years (mean age, 11.4 y). The concentration of the drug was as high as 2.7 mg/mL (8 mg/3 mL) with an addition of dexamethasone. The mean sessions of injection were 1.6 (1-3 sessions). Repeated injection interval was 4 to 6 weeks. The follow-up period was 6 months to 4 years after the last treatment, and the mean follow-up time was 18 months. The results were evaluated based on clinical examination and Doppler ultrasonography scan. The clinical follow-up showed excellent response in 28 of the 32 patients, whereas 4 of the 32 patients also had a satisfactory response. No serious complications were encountered. Intralesional injection of high concentration of bleomycin A5 was an effective and safe treatment of huge macrocystic LMs in the cervical region and can obtain satisfactory results esthetically and functionally without surgery.

Unveiling an anoikis-related risk model and the role of RAD9A in colon cancer.

OBJECTIVE: Colorectal cancer (CRC), specifically colon adenocarcinoma, is the third most prevalent and the second most lethal form of cancer. Anoikis is found to be specialized form of programmed cell death (PCD), which plays a pivotal role in tumor progression. This study aimed to investigate the role of the anoikis related genes (ARGs) in colon cancer. METHODS: Consensus unsupervised clustering, differential expression analysis, tumor mutational burden analysis, and analysis of immune cell infiltration were utilized in the study. For the analysis of RNA sequences and clinical data of COAD patients, data from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) were obtained. A prognostic scoring system for overall survival (OS) prediction was developed using Cox regression and LASSO regression analysis. Furthermore, loss-of-function assay was utilized to explore the role of RAD9A played in the progression of colon cancer. RESULTS: The prognostic value of a risk score composed of NTRK2, EPHA2, RAD9A, CDC25C, and SNAI1 genes was significant. Furthermore, these findings suggested potential mechanisms that may influence prognosis, supporting the development of individualized treatment plans and management of patient outcomes. Further experiments confirmed that RAD9A could promote proliferation and metastasis of colon cancer cells. These effects may be achieved by affecting the phosphorylation of AKT. CONCLUSION: Differences in survival time and the tumor immune microenvironment (TIME) were observed between two gene clusters associated with ARGs. In addition, a prognostic risk model was established and confirmed as an independent risk factor. Furthermore, our data indicated that RAD9A promoted tumorigenicityby activating AKT in colon cancer.

Raman spectra of oleic acid and linoleic acid.

Different unsaturated fatty acids have different physiological functions, however, the common fatty acid products are mostly mixture of several unsaturated fatty acids. Thus it is necessary to analyze the composition of impure fatty acid products before application. In the present article, the Raman spectra of oleic acid and linoleic acid (the most commonly appearing components of fatty acid products) were measured. Furthermore, the mode assignments of the Raman bands were determined and the molecular conformational characters were analyzed. The results lay the groundwork for researching the energy level structures and transitions of long-chain unsaturated fatty acids and enrich the valence bond data of organic molecules. In addition, the differences between the Raman spectra of oleic acid and linoleic acid were analyzed in detail, which provides a convenient and effective method for their identification and has directive significance for the application of Raman spectroscopy in hogwash oil detection.

Effects of Photobiomodulation Therapy on Hard Tissue Healing in Rat Tooth Extraction Sockets.

Objective: To investigate the effects of photobiomodulation therapy (PBMT) on hard tissue healing in rat maxillary first molar extraction sockets. Methods: A total of 20 male Wistar rats were used in the study. The right extraction sockets were irradiated with a Ga-Al-As laser (500 mW, 980 nm) for 51.7 J/cm2 every 24 h for 7 days, while the left sockets served as controls. Rats were sacrificed on days 3, 7, 14, and 28 after tooth extraction, and microcomputed tomography (CT) analysis, histopathological evaluation, and enzyme-linked immunosorbent assay (ELISA) were conducted at different time points. Results: Micro-CT analysis showed that the percentage of bone volume/tissue volume (TV) and bone mineral density were significantly higher in the experimental group compared to the control group on day 28 (p < 0.05). Histopathological evaluation revealed that PBMT promoted new bone formation and accelerated bone remodeling. ELISA demonstrated a significant increase in alkaline phosphatase expression in the laser sides on days 7 and 14 (p < 0.05). Conclusions: One application postextraction followed by seven consecutive daily applications of PBMT can effectively promote hard tissue healing in rat maxillary first molar extraction sockets.

IRAK2-NF-κB signaling promotes glycolysis-dependent tumor growth in pancreatic cancer.

BACKGROUND: Metabolic reprogramming has emerged as a core hallmark of cancer, and cancer metabolism has long been equated with aerobic glycolysis. Moreover, hypoxia and the hypovascular tumor microenvironment (TME) are major hallmarks of pancreatic ductal adenocarcinoma (PDAC), in which glycolysis is imperative for tumor cell survival and proliferation. Here, we explored the impact of interleukin 1 receptor-associated kinase 2 (IRAK2) on the biological behavior of PDAC and investigated the underlying mechanism. METHODS: The expression pattern and clinical relevance of IRAK2 was determined in GEO, TCGA and Ren Ji datasets. Loss-of-function and gain-of-function studies were employed to investigate the cellular functions of IRAK2 in vitro and in vivo. Gene set enrichment analysis, Seahorse metabolic analysis, immunohistochemistry and Western blot were applied to reveal the underlying molecular mechanisms. RESULTS: We found that IRAK2 is highly expressed in PDAC patient samples and is related to a poor prognosis. IRAK2 knockdown led to a significant impairment of PDAC cell proliferation via an aberrant Warburg effect. Opposite results were obtained after exogenous IRAK2 overexpression. Mechanistically, we found that IRAK2 is critical for sustaining the activation of transcription factors such as those of the nuclear factor-κB (NF-κB) family, which have increasingly been recognized as crucial players in many steps of cancer initiation and progression. Treatment with maslinic acid (MA), a NF-κB inhibitor, markedly attenuated the aberrant oncological behavior of PDAC cells caused by IRAK2 overexpression. CONCLUSIONS: Our data reveal a role of IRAK2 in PDAC metabolic reprogramming. In addition, we obtained novel insights into how immune-related pathways affect PDAC progression and suggest that targeting IRAK2 may serve as a novel therapeutic approach for PDAC.

Effect of end groups on the raman spectra of lycopene and ß-carotene under high pressure.

The Raman spectra of all-trans-lycopene in n-hexane were measured under high pressure, and the results compared with those of ß-carotene. The different pressure effects on Raman spectra are analyzed taking into account the different structures of lycopene and ß-carotene molecules. It is concluded that: (a) the vibronic coupling between the S1 and S0 states of ß-carotene is stronger than that of lycopene, (b) the diabatic frequency increment of the ν1 mode is more susceptible to pressure than that of the ν2 mode for lycopene, and (c) ß-rings rotation can relieve the pressure effect on the C=C bond length in ß-carotene. This work provides some insights for elucidating the structural and environmental effects on Raman spectra of carotenoids.

CD74 promotes perineural invasion of cancer cells and mediates neuroplasticity via the AKT/EGR-1/GDNF axis in pancreatic ductal adenocarcinoma.

Perineural invasion (PNI) is a common feature of pancreatic ductal adenocarcinoma (PDAC) and is one of the important causes of local recurrence in resected pancreatic cancer, but the molecular mechanism remains largely unexplored. Here, we used immunohistochemistry staining to determine the expression of CD74. Then the in vivo PNI model, in vitro neuroplasticity assay, cell proliferation assay, wound healing and Transwell-based invasion assay were performed to examine the function of CD74 in pancreatic cancer cell lines. ChIP assay and Luciferase reporter assay were used to illustrate the mechanism underlying CD74 induced GDNF expression. We confirmed that the expression level of CD74 was an independent predictor of PNI and poor prognosis for PDAC. Moreover, we found that upregulation of CD74 on PDAC enhanced its migration and invasive capabilities and potentiated the secretion of neurotrophic factor GDNF to promote the neuroplasticity. Mechanistically, CD74 promoted GDNF production via the AKT/EGR-1/GDNF axis in PDAC. Taken together, our findings suggest a supportive role of CD74 in the PNI of PDAC, and deepen our understanding of how cancer cells promote neuroplasticity in the microenvironment of PDAC.