Acute pulpitis promotes purinergic signaling to induce pain in rats via P38MAPK/NF-κB signaling pathway.

Toothache is one of the most common types of pain, but the mechanisms underlying pulpitis-induced pain remain unknown. The ionotropic purinergic receptor family (P2X) is reported to mediate nociception in the nervous system. This study aims to investigate the involvement of P2X3 in the sensitisation of the trigeminal ganglion (TG) and the inflammation caused by acute pulpitis. An acute tooth inflammation model was established by applying LPS to the pulp of SD rats. We found that the increased expression of P2X3 was induced by acute pulpitis. A selective P2X3 inhibitor (A-317491) reduced pain-like behavior in the maxillofacial region of rats and depressed the activation of neurons in the trigeminal ganglion induced by pulpitis. The upregulated MAPK signaling (p-p38, p-ERK1/2) expression in the ipsilateral TG induced by pulpitis could also be depressed by the application of the P2X3 inhibitor. Furthermore, the expression of markers of inflammatory processes, such as NF-κB, TNF-α and IL-1ß, could be induced by acute pulpitis and deduced by the intraperitoneal injection of P2X3 antagonists. Our findings demonstrate that purinergic P2X3 receptor signaling in TG neurons contributes to pulpitis-induced pain in rats and that P2X3 signaling may be a potential therapeutic target for tooth pain.

Impact of PEGDA photopolymerization in micro-stereolithography on 3D printed hydrogel structure and swelling.

3D printing complex architectures of responsive-hydratable polymers are enabled by stereolithography via photopolymerization. Yet, insufficient crosslinking leads to compromised structural integrity of the photopolymerized samples, which affects the functionality and reliability of hydrogel devices significantly. Here we investigate how curing parameters and ink formulation affect 3D printed PEGDA samples by using a combination of microfabrication, structural characterization, and reactive coarse-grained molecular dynamics simulation. Our findings show that the degree of curing exhibits a graded profile from confocal Raman spectroscopy and submicron pores from atomic force microscopy, both of which are also observed in our molecular simulations. Moreover, with environmental scanning electron microscopy, we probe the microscopic swelling and bending dynamics of 3D printed hydratable PEGDA structures as well as their structural integrity. Our in-depth characterization results reveal how hydrogel elasticity and irreversible densification due to pore formation highly depends on the exposure time, light intensity and the associated degree of crosslinking. This work provides new molecular insights into processing-structure relation in stereolithography 3D printing.

Analysis of Aldo-Keto Reductase Gene Family and Their Responses to Salt, Drought, and Abscisic Acid Stresses in Medicago truncatula.

Salt and drought stresses are two primary abiotic stresses that inhibit growth and reduce the activity of photosynthetic apparatus in plants. Abscisic acid (ABA) plays a key role in abiotic stress regulation in plants. Some aldo-keto reductases (AKRs) can enhance various abiotic stresses resistance by scavenging cytotoxic aldehydes in some plants. However, there are few comprehensive reports of plant AKR genes and their expression patterns in response to abiotic stresses. In this study, we identified 30 putative AKR genes from Medicago truncatula. The gene characteristics, coding protein motifs, and expression patterns of these MtAKRs were analyzed to explore and identify candidate genes in regulation of salt, drought, and ABA stresses. The phylogenetic analysis result indicated that the 52 AKRs in Medicago truncatula and Arabidopsis thaliana can be divided into three groups and six subgroups. Fifteen AKR genes in M. truncatula were randomly selected from each group or subgroup, to investigate their response to salt (200 mM of NaCl), drought (50 g·L-1 of PEG 6000), and ABA (100 µM) stresses in both leaves and roots. The results suggest that MtAKR1, MtAKR5, MtAKR11, MtAKR14, MtAKR20, and MtAKR29 may play important roles in response to these stresses.

The purinergic receptor P2X3 promotes facial pain by activating neurons and cytokines in the trigeminal ganglion.

The mechanism underlying allodynia/hyperalgesia caused by dental pulpitis has remained enigmatic. This investigation endeavored to characterize the influence of the purinergic receptor P2X3 on pain caused by experimental pulpitis and the mechanism involved. An experimental model of irreversible pulpitis was produced by the drilling and exposure of the dental pulp of the left upper first and second molars in rats, followed by measuring nociceptive responses in the oral and maxillofacial regions. Subsequently, neuronal activity and the expression of P2X3 and pertinent cytokines in the trigeminal ganglion (TG) were meticulously examined and analyzed. Histological evidence corroborated that significant pulpitis was produced in this model, which led to a distinct escalation in nociceptive responses in rats. The activation of neurons, coupled with the upregulated expression of c-fos, P2X3, p-p38, TNF-α and IL-1ß, was identified subsequent to the pulpitis surgery within the TG. The selective inhibition of P2X3 with A-317491 effectively restrained the abnormal allodynia/hyperalgesia following the pulpitis surgery and concurrently inhibited the upregulation of p-p38, TNF-α and IL-1ß within the TG. These findings suggest that the P2X3 signaling pathway plays a pivotal role in instigating and perpetuating pain subsequent to the induction of pulpitis in rats, implicating its association with the p38 MAPK signaling pathway and inflammatory factors.

Perspective insights into versatile hydrogels for stroke: From molecular mechanisms to functional applications.

As the leading killer of life and health, stroke leads to limb paralysis, speech disorder, dysphagia, cognitive impairment, mental depression and other symptoms, which entail a significant financial burden to society and families. At present, physiology, clinical medicine, engineering, and materials science, advanced biomaterials standing on the foothold of these interdisciplinary disciplines provide new opportunities and possibilities for the cure of stroke. Among them, hydrogels have been endowed with more possibilities. It is well-known that hydrogels can be employed as potential biosensors, medication delivery vectors, and cell transporters or matrices in tissue engineering in tissue engineering, and outperform many traditional therapeutic drugs, surgery, and materials. Therefore, hydrogels become a popular scaffolding treatment option for stroke. Diverse synthetic hydrogels were designed according to different pathophysiological mechanisms from the recently reported literature will be thoroughly explored. The biological uses of several types of hydrogels will be highlighted, including pro-angiogenesis, pro-neurogenesis, anti-oxidation, anti-inflammation and anti-apoptosis. Finally, considerations and challenges of using hydrogels in the treatment of stroke are summarized.

Extracorporeal shock wave lithotripsy is effective in treating single melamine induced urolithiasis in infants and young children.

PURPOSE: We evaluated the safety and efficacy of extracorporeal shock wave lithotripsy in the treatment of single melamine induced urolithiasis in infants and young children. MATERIALS AND METHODS: A total of 189 infants and young children with single melamine induced urolithiasis were referred to our center for treatment with extracorporeal shock wave lithotripsy between March 2009 and July 2010. Location of the calculus was proximal ureteral in 17 patients, mid ureteral in 5, distal ureteral in 26 and kidney in 141. Stone size ranged from 3.8 to 25 mm (mean ± SD 9.79 ± 3.83). RESULTS: All patients underwent extracorporeal shock wave lithotripsy using the same device with an energy ranging from 8 to 12 kV. Stone-free rate was 97.88%, clinically insignificant residual fragment rate was 1.59% and repeat treatment rate was 2.65%. A total of 180 patients (95.24%) required only 1 lithotripsy session and 5 (2.65%) required 2 sessions. Mean ± SD number of shock waves delivered per session was 580.36 ± 190.69 (range 65 to 950). Extracorporeal shock wave lithotripsy failed to fragment stones in only 1 infant, who had a proximal ureteral stone. A total of 181 specimens were collected and analyzed by infrared spectrum, with results demonstrating that the main composition was uric acid and melamine. All patients were followed for a mean of 28 months (range 20 to 36). No severe complication, such as renal subcapsular hemorrhage, hypertension, kidney rupture or lung injury, was observed. CONCLUSIONS: Extracorporeal shock wave lithotripsy with low energy can effectively disintegrate melamine induced calculi. This approach has become our preferred method for treating single melamine induced urolithiasis in infants and young children.

Association between oral microflora and gastrointestinal tumors (Review).

The oral cavity contains the highest density and the most species of microorganisms compared with other parts of the body. Recent studies have determined that the species and abundance of oral microflora are closely associated with the development of upper gastrointestinal tumors, including oral, esophageal and gastric cancer. Additionally, differential abundant microbiota in patients with cancer and abnormal microorganisms inside the tumor tissue have been identified as critical markers of tumorigenesis. There is evidence to suggest that certain genera, including Firmicutes, along with various species, such as Porphyromonas, can increase the risk of oral cancer. Furthermore, Porphyromonas gingivalis is a risk factor for esophageal carcinoma, while Helicobacter pylori infections are a main cause of gastric cancer. Currently, as far as carcinogenic mechanisms of oral microorganisms are concerned, it has been hypothesized that the production of carcinogenic substances, chronic inflammation and altered cell metabolisms may be mechanisms by which oral microorganisms influence the development of upper gastrointestinal cancer. Certain phrases, including 'oral microbes', 'oral microorganism', 'oral microbiology', 'oral microflora', 'oral cancer', 'oral carcinoma', 'carcinoma of mouth', 'esophagus cancer', 'esophageal cancer', 'esophageal carcinoma', 'carcinoma of esophagus', 'gastric cancer', 'gastric carcinoma', 'stomach cancer', 'cancer of the stomach', 'carcinogenic mechanism' and 'carcinogenesis', were searched as key words in PubMed and Web of Science for articles published between 1975 to 2020. A total of 1,512 studies were obtained. After further searching the abstracts for key words, such as oral microorganisms, oral cancer, esophagus cancer, gastric cancer and carcinogenic mechanisms, 137 studies were selected. The current review systematically and comprehensively summarized the association between the oral microbiota and oral, esophageal and gastric cancer. Additionally, the current review described the carcinogenic mechanisms of oral microbes and attempted to identify common molecular mechanisms among different types of tumor. The association between upper gastrointestinal cancer therapy and oral microflora was also assessed. The present review may be used as a reference for future diagnosis and therapeutics for upper gastrointestinal tumors.

Comparison between Dexmedetomidine and Midazolam for Sedation in Patients with Intubation after Oral and Maxillofacial Surgery.

The aim of the investigation is to clarify the beneficial sedative effects for patients with postoperative intubation in the intensive care unit (ICU) after oral and maxillofacial surgery. Forty patients with postoperative intubation were divided into two groups in method of random number table: midazolam group and dexmedetomidine group. The Ramsay score, the behavioral pain scale (BPS) score, SpO2, HR, MAP, and RR were recorded before sedation (T0), 30 minutes (T1), 1 hour (T2), 2 hours (T3), 6 hours (T4), and 12 hours (T5) after dexmedetomidine or midazolam initiation in intensive care unit, and 10 minutes after extubation (T6). The rate of incidences of side effects was calculated. Sedation with midazolam was as good as standard sedation with dexmedetomidine in maintaining target sedation level. The BPS score in the midazolam group was higher than that in the dexmedetomidine group. The time of tracheal catheter extraction in the dexmedetomidine group was shorter than that in the midazolam group (p ≤ 0.001). The incidence of bradycardia in the dexmedetomidine group was higher than that in the midazolam group (p = 0.028). There was no statistically significant difference in the incidence of hypotension between the two groups (p = 0.732). The incidence of respiratory depression of group midazolam was higher than that of group dexmedetomidine (p = 0.018). The incidence of delirium in the dexmedetomidine group was significantly lower than that in the midazolam group, and the difference was statistically significant (p = 0.003). Dexmedetomidine and midazolam can meet the needs for sedation in ICU patients. And dexmedetomidine can improve patients' ability to communicate pain compared with midazolam.

Comparison of Intranasal Dexmedetomidine and Oral Midazolam for Premedication in Pediatric Dental Patients under General Anesthesia: A Randomised Clinical Trial.

The aim of this study was to compare the effects of preoperative intranasal dexmedetomidine and oral midazolam on preoperative sedation and postoperative agitation in pediatric dentistry. A total of 60 children (ASA grade I, aged 3-6 years) scheduled for elective pediatric dental treatment were randomly divided into the dexmedetomidine (DEX) and midazolam (MID) groups. Ramsay sedation score, parental separation anxiety scale, mask acceptance scale, pediatric anesthesia emergence delirium scale, and hemodynamic parameters were recorded. The Ramsay sedation scale and hemodynamic parameters of the children were observed and recorded immediately before administration and 10, 20, and 30 min after administration. A satisfactory mask acceptance scale rate was 93.33% in both MID and DEX groups, and there was no significant difference between the two groups (p > 0.05). The proportions of children that "successfully separated from their parents" were 93.33% (MID) and 96.67% (DEX). No significant difference was found between the two groups (p > 0.05). The incidence of agitation was 20% in the MID group and 0% in the DEX group, and the difference was statistically significant (p < 0.05). Intranasal dexmedetomidine and oral midazolam provided satisfactory sedation. No significant difference between the two groups was found in terms of parental separation anxiety and mask acceptance (p > 0.05). The incidence of postoperative pediatrics emergence delirium was significantly lower in the DEX group (p < 0.05).

Comparison in Sedative Effects between Dexmedetomidine and Midazolam in Dental Implantation: A Randomized Clinical Trial.

Dexmedetomidine refers to an α 2-adrenergic receptor agonist causing potent sedative, analgesic, and minimal respiratory depression compared with alternative drugs. The present study was aimed at comparing the efficaciousness and safety of midazolam and dexmedetomidine as sedatives for dental implantation. We recruited 60 patients belonging to group I or II of the American Society of Anesthesiologists (ASA) and treated them with either midazolam or dexmedetomidine in a random manner. Patients' duration of analgesia after surgery, surgeon and patient degrees of satisfaction, Observer's Assessment of Alertness/Sedation Scale (OAAS) scores after drug administration, visual analogue scale (VAS) pain scores, and vital signs were recorded variables. Patients administered dexmedetomidine had significantly lower OAAS scores than those administered midazolam (p < 0.05). Patients administrated dexmedetomidine had a significantly longer analgesia duration after the surgical procedure than those administered midazolam, and the difference was statistically significant (p < 0.05). Dexmedetomidine had a significantly larger number of surgeons satisfied with the level of sedation/analgesia than midazolam (p < 0.05). Accordingly, it is considered that dexmedetomidine can achieve better postoperative analgesia, surgeon satisfaction, and sedation than midazolam.