Emodin suppresses oxaliplatin-induced neuropathic pain by inhibiting COX2/NF-κB mediated spinal inflammation.

Oxaliplatin (OXA) is a common chemotherapy drug for colorectal, gastric, and pancreatic cancers. The anticancer effect of OXA is often accompanied by neurotoxicity and acute and chronic neuropathy. The symptoms present as paresthesia and pain which adversely affect patients' quality of life. Herein, five consecutive intraperitoneal injections of OXA at a dose of 4 mg/kg were used to mimic chemotherapy. OXA administration induced mechanical allodynia, activated spinal astrocytes, and increased inflammatory response. To develop an effective therapeutic measure for OXA-induced neuropathic pain, emodin was intrathecally injected into OXA rats. Emodin developed an analgesic effect, as demonstrated by a significant increase in the paw withdrawal threshold of OXA rats. Moreover, emodin treatment reduced the pro-inflammatory cytokines (tumor necrosis factor-α and interleukin-1ß) which upregulated in OXA rats. Furthermore, autodock data showed four hydrogen bonds were formed between emodin and cyclooxygenase-2 (COX2), and emodin treatment decreased COX2 expression in OXA rats. Cell research further proved that emodin suppressed nuclear factor κB (NF-κB)-mediated inflammatory signal and reactive oxygen species level. Taken together, emodin reduced spinal COX2/NF-κB mediated inflammatory signal and oxidative stress in the spinal cord of OXA rats which consequently relieved OXA-induced neuropathic pain.

Glycogen synthase kinase-3ß inhibition decreases inflammation and relieves cancer induced bone pain via reducing Drp1-mediated mitochondrial damage.

Bone is the preferential site of metastasis for breast cancer. Invasion of cancer cells induces the destruction of bone tissue and damnification of peripheral nerves and consequently induced central sensitization which contributes to severe pain. Herein, cancer induced bone pain (CIBP) rats exhibited destruction of tibia, mechanical allodynia and spinal inflammation. Inflammatory response mainly mediated by astrocyte and microglia in central nervous system. Our immunofluorescence analysis revealed activation of spinal astrocytes and microglia in CIBP rats. Transmission electron microscopy (TEM) observations of mitochondrial outer membrane disruption and cristae damage in spinal mitochondria of CIBP rats. Proteomics analysis identified abnormal expression of proteins related to mitochondrial organization and function. Intrathecally, injection of GSK-3ß activity inhibitor TDZD-8 significantly attenuated Drp1-mediated mitochondrial fission and recovered mitochondrial function. Inhibition of GSK-3ß activity also suppressed NLRP3 inflammasome cascade and consequently decreased mechanical pain sensitivity of CIBP rats. For cell research, TDZD-8 treatment significantly reversed TNF-α induced mitochondrial membrane potential (MMP) deficiency and high mitochondrial reactive oxygen species level. Taken together, GSK-3ß inhibition by TDZD-8 decreases spinal inflammation and relieves cancer induced bone pain via reducing Drp1-mediated mitochondrial damage.

Emodin alleviates arthritis pain through reducing spinal inflammation and oxidative stress.

Chronic pain is the predominant problem for rheumatoid arthritis patients, and negatively affects quality of life. Arthritis pain management remains largely inadequate, and developing new treatment strategies are urgently needed. Spinal inflammation and oxidative stress contribute to arthritis pain and represent ideal targets for the treatment of arthritis pain. In the present study, collagen-induced arthritis (CIA) mouse model was established by intradermally injection of type II collagen (CII) in complete Freund's adjuvant (CFA) solution, and exhibited as paw and ankle swelling, pain hypersensitivity and motor disability. In spinal cord, CIA inducement triggered spinal inflammatory reaction presenting with inflammatory cells infiltration, increased Interleukin-1ß (IL-1ß) expression, and up-regulated NOD-like receptor thermal protein domain associated protein 3 (NLRP3) and cleaved caspase-1 levels, elevated spinal oxidative level presenting as decreased nuclear factor E2-related factor 2 (Nrf2) expression and Superoxide dismutase (SOD) activity. To explore potential therapeutic options for arthritis pain, emodin was intraperitoneally injected for 3 days on CIA mice. Emodin treatment statistically elevated mechanical pain sensitivity, suppressed spontaneous pain, recovered motor coordination, decreased spinal inflammation score and IL-1ß expression, increased spinal Nrf2 expression and SOD activity. Further, AutoDock data showed that emodin bind to Adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) through two electrovalent bonds. And emodin treatment increased the phosphorylated AMPK at threonine 172. In summary, emodin treatment activates AMPK, suppresses NLRP3 inflammasome response, elevates antioxidant response, inhibits spinal inflammatory reaction and alleviates arthritis pain.

Dental expenditure, progressivity and horizontal inequality in Chinese adults: based on the 4th National Oral Health Epidemiology Survey.

BACKGROUND: The financial burden of oral diseases is a growing concern as the medical expenses rise worldwide. The aim of this study was to investigate the dental expenditure, analyze its progressivity and horizontal inequality under the general health finance and insurance system, and identify the key social determinants of the inequality for Chinese adults. METHODS: A secondary analysis used the data of 13,464 adults from the 4th National Oral Health Epidemiological Survey (NOHES) in China was undertaken. The dental expenditure was collected and divided into out-of-pocket and health insurance payments. Horizontal inequality index and Kakwani index were used to analyze the horizontal inequality and progressivity, respectively. The decomposition model of the concentration index was set up to explore the associated socioeconomic determinants. RESULTS: The results showed that a mean dental expenditure per capita of Chinese adults was $20.55 (95% Confidence Interval-CI: 18.83,22.26). Among those who actually used dental service, the cost was $100.95 (95%CI: 93.22,108.68). Over 90% of dental spending was due to out-of-pocket expenses. For self-reported oral health, the horizontal inequality index was - 0.1391 and for the decayed tooth (DT), it was - 0.2252. For out-of-pocket payment, the Kakwani index was - 0.3154 and for health insurance payment it was - 0.1598. Income, residential location, educational attainment, oral hygiene practice, self-reported oral health, age difference were the main contributors to the inequality of dental expenditure. CONCLUSION: Dental expenditure for Chinese adults was at a lower level due to underutilization. The ratio of payments of dental expenditure and utilization was disproportional, whether it was out-of-pocket or insurance payment. Individuals who were more in need of oral care showed less demand for service or not required service in time. For future policy making on oral health, it is worth the effort to further promote the awareness of the importance of oral health and utilization of dental service.

A Novel Air-Cooled Nd:YAG Laser for the Treatment of the Venous Lakes of the Lips.

Objective: To evaluate the therapeutic effect of a novel air-cooled Nd:YAG laser in the venous lakes of the lips (VLL). Background: The thermal injury is one of the most important issues during laser therapy for venous lakes. Methods: Six pieces of fresh pork livers were used to provide 30 regions with a diameter of 6 mm for experiment in vitro, among which 15 regions were treated by Nd:YAG laser with air cooling until the tissue turned gray-white, whereas the rest were treated without air cooling as control. The operation time of laser irradiation, the degree of temperature increase, and the depth of coagulation tissue were compared between two groups. Then, 60 VLL patients were selected for Nd:YAG laser treatment with or without air cooling. The operation time of laser irradiation, the degree of temperature increase, the postoperative pain visual analog scale (VAS) score, and the percentage of lesions removed within 1 month were compared. Results: In tissue studies, the treated group showed a longer operation time of laser irradiation (p < 0.01), a lower degree of temperature increase (p < 0.01), and there was no significant statistical difference in the depth of coagulation tissue (p = 0.624). In clinical studies, the treated group showed a longer operation time of laser irradiation (p < 0.01), a lower degree of temperature increase (p < 0.01), and a lower VAS score on the 1st and 2nd day, compared with the control group (p < 0.01). Conclusions: Air cooling during Nd:YAG laser for the treatment of VLL can prolong the surgical time, but lowered tissue temperature and reduced patient pain within 2 days under the premise of ensuring the treatment effect.

Alleviating effect of lycorine on CFA­induced arthritic pain via inhibition of spinal inflammation and oxidative stress.

Chronic pain is the primary symptom of osteoarthritis affecting a patient's quality of life. Neuroinflammation and oxidative stress in the spinal cord contribute to arthritic pain and represent ideal targets for pain management. In the present study, a model of arthritis was established by intra-articular injection of complete Freund's adjuvant (CFA) into the left knee joint in mice. After CFA inducement, knee width and pain hypersensitivity in the mice were increased, motor disability was impaired, spinal inflammatory reaction was induced, spinal astrocytes were activated, antioxidant responses were decreased, and glycogen synthase kinase 3ß (GSK-3ß) activity was inhibited. To explore the potential therapeutic options for arthritic pain, lycorine was intraperitoneally injected for 3 days in the CFA mice. Lycorine treatment significantly reduced mechanical pain sensitivity, suppressed spontaneous pain, and recovered motor coordination in the CFA-induced mice. Additionally, in the spinal cord, lycorine treatment decreased the inflammatory score, reduced NOD-like receptor protein 3 inflammasome (NLRP3) activity and IL-1ß expression, suppressed astrocytic activation, downregulated NF-κB levels, increased nuclear factor erythroid 2-related factor 2 expression and superoxide dismutase activity. Furthermore, lycorine was shown to bind to GSK-3ß through three electrovalent bonds, to inhibit GSK-3ß activity. In summary, lycorine treatment inhibited GSK-3ß activity, suppressed NLRP3 inflammasome activation, increased the antioxidant response, reduced spinal inflammation, and relieved arthritic pain.

The Use of 810 and 1064 nm Lasers on Dental Implants: In Vitro Analysis of Temperature, Surface Alterations, and Biological Behavior in Human Gingival Fibroblasts.

Objective: The primary objective of this study was to evaluate the safety of 810 and 1064 nm laser treatment on dental implants. Background: Peri-implantitis is a challenge for clinicians and researchers. Methods: A pig mandible model was used to evaluate temperature increases during laser irradiation. Surface alterations on processed pure titanium discs were analyzed via scanning electron microscopy and measurement of surface contact angles. Processed titanium discs were cocultured in vitro with human gingival fibroblasts; subsequently, cell proliferation was measured. Results: The maximum temperature and time to reach each threshold were comparable. No surface alterations were detected after 810 nm laser irradiation, whereas surface cracks were observed after 1064 nm laser irradiation under the parameter setting of 31.84 W/cm2. Compared with unaltered processed pure titanium discs, the proliferation of human gingival fibroblasts was significantly greater on altered processed pure titanium discs. Conclusions: The use of either 810 or 1064 nm laser treatments may increase the risk of thermal damage in terms of increased temperature if the parameter setting is not warranted. In addition, the use of 1064 nm laser treatment could lead to changes in pure titanium discs that do not negatively affect cell proliferation. Further investigations of laser-assisted therapy are necessary to improve guidelines concerning the treatment of peri-implantitis. Clinical trial registration number: 2021-P2-098-01.

2-Bromopalmitate decreases spinal inflammation and attenuates oxaliplatin-induced neuropathic pain via reducing Drp1-mediated mitochondrial dysfunction.

Oxaliplatin (OXA) is a third-generation platinum compound with clinical activity in multiple solid tumors. Due to the repetition of chemotherapy cycle, OXA-induced chronic neuropathy presenting as paresthesia and pain. This study explored the neuropathy of chemotherapy pain and investigated the analgesic effect of 2-bromopalmitate (2-BP) on the pain behavior of OXA-induced rats. The chemotherapy pain rat model was established by the five consecutive administration of OXA (intraperitoneal, 4 mg/kg). After the establishment of OXA-induced rats, the pain behavior test, inflammatory signal analysis and mitochondrial function measurement were conducted. OXA-induced rats exhibited mechanical allodynia and spinal inflammatory infiltration. Our fluorescence and western blot analysis revealed spinal astrocytes were activated in OXA rats with up-regulation of astrocytic markers. In addition, NOD-, LRR- and pyrin domain-containing 3 (NLRP3) inflammasome mediated inflammatory signal cascade was also activated. Inflammation was triggered by dysfunctional mitochondria which represented by increase in cyclooxygenase-2 (COX-2) level and manganese superoxide dismutase (Mn-SOD) activity. Intrathecally injection of 2-BP significantly attenuated dynamin-related protein 1 (Drp1) mediated mitochondrial fission, recovered mitochondrial function, suppressed NLRP3 inflammasome cascade, and consequently decreased mechanical pain sensitivity. For cell research, 2-BP treatment significantly reversed tumor necrosis factor-α (TNF-α) induced mitochondria membrane potential deficiency and high reactive oxygen species (ROS) level. These findings indicate 2-BP decreases spinal inflammation and relieves OXA-induced neuropathic pain via reducing Drp1-mediated mitochondrial dysfunction.

Associated Factors of Oral Health-related Quality of Life in Chinese Adolescents Aged 12-15 Years.

adolescents aged 12 to 15 years based on the 4th National Oral Health Survey and to explore its associated factors. METHODS: Students aged 12 to 15 years were recruited using to a multistage stratified random sampling method. All the subjects received oral examination and completed a questionnaire. Information relating to OHRQoL was collected through a Mandarin version of the child oral impacts on daily performances (Child-OIDP) questionnaire. The relationship between the Child-OIDP scores and independent variables was assessed using a Mann-Whitney U-test, Kruskal-Wallis test and a multivariate Poisson regression. RESULTS: A total of 89,582 subjects were included in the analysis, of whom 76.6% reported oral impacts in the last 6 months. Eating was the most affected daily performance. The results of the regression analysis showed that factors associated with adolescents' OHRQoL included sex, location of residence, region, only child status, parents' level of education, frequency of sugar consumption, self-perception of general/oral health, dental appointments in the past 12 months, oral health knowledge status, age, decayed, missing and filled teeth (DMFT) index and number of teeth with gingival bleeding. CONCLUSION: Oral impacts were common among Chinese adolescents, although most were not so severe. Eating was the most commonly affected performance. Sex, location of residence, region, only child status, parents' level of education, frequency of sugar consumption, selfperception of general/oral health status, dental appointments in the previous 12 months, oral health knowledge status, age, DMFT index and number of teeth with gingival bleeding were found to be associated with OHRQoL.

Cost-effectiveness Analysis of Comprehensive Oral Health Care for Severe Early Childhood Caries in Urban Beijing, China.

OBJECTIVE: To evaluate the cost-effectiveness of comprehensive oral health care for severe early childhood caries (S-ECC) in urban Beijing, China. METHODS: A randomised cluster sampling method was used to select 187 children aged 3 to 5 years with S-ECC from two kindergartens in urban Beijing. Comprehensive oral health care and questionnaires for the parents/guardians were provided to the test group, while an oral health examination and questionnaires for the parents/guardians were provided to the control group. Data were collected and a Markov model was established for a cost-effectiveness analysis. RESULTS: One year later, 614 RMB yuan and 184 RMB yuan were needed for the control and test group, respectively, to reduce one average decayed tooth. The cost for the test group was continuously lower than for the control group during the 4-year simulation. The cumulative cost for the test group was lower than for the control group when the model was circulated for more than 1.5 years. At this time, the change of decayed teeth was stable in the test group. CONCLUSION: Comprehensive oral health care had extraordinary cost-effectiveness for S-ECC. The optimal time to process S-ECC may be after 1.5 years.

Exogenous trehalose confers high temperature stress tolerance to herbaceous peony by enhancing antioxidant systems, activating photosynthesis, and protecting cell structure.

Herbaceous peony (Paeonia lactiflora Pall.) is an excellent ornamental plant, which is usually stressed by summer high temperatures, but little is known about its relevant measures. In this study, the effects of trehalose on alleviating high temperature-induced damage in P. lactiflora were examined. High temperature stress in P. lactiflora increased production of reactive oxygen species (ROS), including superoxide anion free radical (O2·-) and hydrogen peroxide (H2O2), enhanced both malondialdehyde (MDA) content and relative electrical conductivity (REC), decreased superoxide dismutase (SOD) activity, increased catalase (CAT) activity, inhibited photosynthesis, and destroyed cell structure. However, exogenous trehalose effectively alleviated its high temperature-induced damage. Trehalose decreased O2·- and H2O2 accumulation, MDA content, and REC, increased the activities of antioxidant enzymes, enhanced photosynthesis, improved cell structure, and made chloroplasts rounder. Additionally, trehalose induced high temperature-tolerant-related gene expressions to different degrees. These results indicated that trehalose decreased the deleterious effect of high temperature stress on P. lactiflora growth by enhancing antioxidant systems, activating photosynthesis, and protecting cell structure. These findings indicate the potential application of trehalose for managing high temperatures in P. lactiflora cultivation.

Utilisation of Oral Health Services and Economic Burden of Oral Diseases in China.

OBJECTIVE: To evaluate the use of oral health services, the economic burden of oral diseases and related influential factors in China. METHOD: Using the multistage, stratified, equal proportion, random sampling method in the 4th National Oral Health Survey of China conducted in 2015 to 2016, residents aged 3 to 5 years, 12 to 15 years, 35 to 44 years, 55 to 64 years, and 65 to 74 years respectively were recruited, clinically examined and answered a questionnaire. Utilisation of oral health services were assessed in all the age groups and the economic burden of oral diseases in the past 12 months were assessed in the 3 to 5 years and 35 to 74 year-old groups. Chi-squared tests, t tests, correlation analysis and a one-way ANOVA were used to determine the relationships of different factors with utilisation of oral health services and the economic burden of oral diseases. RESULTS: In the subject groups - 3 to 5 years, 12 to 15 years and 35 to 74 years - the prevalence of the utilisation of oral health services in the past 12 months was 14.6% (5,876/40,353), 23.6% (27,936/118,592), and 20.1% (2,708/13,461), respectively. In all three groups, receiving dental treatment was the most common reason for subjects' recent dental visit. The average dental cost in the past 12 months was 403.43 CNY (median = 100) for 3 to 5-year-old children and 850.83 CNY (median = 300) for adults aged 35 to 74 years old. Area, education and annual household income per person were the socio-economic influential factors. Oral health status, oral hygiene and attitudes to and knowledge of oral health affected the utilisation of oral health services and the economic burden of oral diseases. CONCLUSION: The percentage of dental service utilisation was relatively low, and the economic burden was high. The related factors for both utilisation of oral health services and the economic burden of oral diseases included living in area, educational attainment, household income, perceived oral health status, and oral hygiene.