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1.
Cell Rep ; 43(4): 114121, 2024 Apr 23.
Article in English | MEDLINE | ID: mdl-38615320

ABSTRACT

Metabolic reprogramming is a hallmark of cancer, enabling cancer cells to rapidly proliferate, invade, and metastasize. We show that creatine levels in metastatic breast cancer cell lines and secondary metastatic tumors are driven by the ubiquitous mitochondrial creatine kinase (CKMT1). We discover that, while CKMT1 is highly expressed in primary tumors and promotes cell viability, it is downregulated in metastasis. We further show that CKMT1 downregulation, as seen in breast cancer metastasis, drives up mitochondrial reactive oxygen species (ROS) levels. CKMT1 downregulation contributes to the migratory and invasive potential of cells by ROS-induced upregulation of adhesion and degradative factors, which can be reversed by antioxidant treatment. Our study thus reconciles conflicting evidence about the roles of metabolites in the creatine metabolic pathway in breast cancer progression and reveals that tight, context-dependent regulation of CKMT1 expression facilitates cell viability, cell migration, and cell invasion, which are hallmarks of metastatic spread.


Subject(s)
Breast Neoplasms , Creatine Kinase, Mitochondrial Form , Reactive Oxygen Species , Animals , Female , Humans , Mice , Breast Neoplasms/pathology , Breast Neoplasms/metabolism , Breast Neoplasms/genetics , Cell Line, Tumor , Cell Movement , Cell Survival , Creatine Kinase , Creatine Kinase, Mitochondrial Form/metabolism , Disease Progression , Gene Expression Regulation, Neoplastic , Mitochondria/metabolism , Neoplasm Invasiveness , Neoplasm Metastasis , Reactive Oxygen Species/metabolism
2.
Photobiomodul Photomed Laser Surg ; 42(3): 230-237, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38417045

ABSTRACT

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.


Subject(s)
Laser Therapy , Lasers, Solid-State , Low-Level Light Therapy , Humans , Lasers, Solid-State/therapeutic use , Lip/surgery , Temperature
3.
Front Genet ; 14: 1230245, 2023.
Article in English | MEDLINE | ID: mdl-37849501

ABSTRACT

Background: Periodontits (PD) and Alzheimer's disease (AD) are both associated with ageing and clinical studies increasingly evidence their association. However, specific mechanisms underlying this association remain undeciphered, and immune-related processes are purported to play a signifcant role. The accrual of publicly available transcriptomic datasets permits secondary analysis and the application of data-mining and bioinformatic tools for biological discovery. Aim: The present study aimed to leverage publicly available transcriptomic datasets and databases, and apply a series of bioinformatic analysis to identify a robust signature of immune-related signature of PD and AD linkage. Methods: We downloaded gene-expresssion data pertaining PD and AD and identified crosstalk genes. We constructed a protein-protein network analysis, applied immune cell enrichment analysis, and predicted crosstalk immune-related genes and infiltrating immune cells. Next, we applied consisent cluster analysis and performed immune cell bias analysis, followed by LASSO regression to select biomarker immune-related genes. Results: The results showed a 3 gene set comprising of DUSP14, F13A1 and SELE as a robust immune-related signature. Macrophages M2 and NKT, B-cells, CD4+ memory T-cells and CD8+ naive T-cells emerged as key immune cells linking PD with AD. Conclusion: Candidate immune-related biomarker genes and immune cells central to the assocation of PD with AD were identified, and merit investigation in experimental and clinical research.

4.
Sci Rep ; 13(1): 18566, 2023 10 30.
Article in English | MEDLINE | ID: mdl-37903851

ABSTRACT

The premetastatic niche hypothesis proposes an active priming of the metastatic site by factors secreted from the primary tumor prior to the arrival of the first cancer cells. We investigated several extracellular matrix (ECM) structural proteins, ECM degrading enzymes, and ECM processing proteins involved in the ECM remodeling of the premetastatic niche. Our in vitro model consisted of lung fibroblasts, which were exposed to factors secreted by nonmalignant breast epithelial cells, nonmetastatic breast cancer cells, or metastatic breast cancer cells. We assessed ECM remodeling in vivo in premetastatic lungs of female mice growing orthotopic primary breast tumor xenografts, as compared to lungs of control mice without tumors. Premetastatic lungs contained significantly upregulated Collagen (Col) Col4A5, matrix metalloproteinases (MMPs) MMP9 and MMP14, and decreased levels of MMP13 and lysyl oxidase (LOX) as compared to control lungs. These in vivo findings were consistent with several of our in vitro cell culture findings, which showed elevated Col14A1, Col4A5, glypican-1 (GPC1) and decreased Col5A1 and Col15A1 for ECM structural proteins, increased MMP2, MMP3, and MMP14 for ECM degrading enzymes, and decreased LOX, LOXL2, and prolyl 4-hydroxylase alpha-1 (P4HA1) for ECM processing proteins in lung fibroblasts conditioned with metastatic breast cancer cell media as compared to control. Taken together, our data show that premetastatic priming of lungs by primary breast tumors resulted in significant ECM remodeling which could facilitate metastasis by increasing interstitial fibrillar collagens and ECM stiffness (Col14A1), disruptions of basement membranes (Col4A5), and formation of leaky blood vessels (MMP2, MMP3, MMP9, and MMP14) to promote metastasis.


Subject(s)
Breast Neoplasms , Mammary Neoplasms, Animal , Humans , Female , Mice , Animals , Matrix Metalloproteinase 2/metabolism , Matrix Metalloproteinase 9/metabolism , Matrix Metalloproteinase 14/metabolism , Matrix Metalloproteinase 3/metabolism , Lung/pathology , Extracellular Matrix/metabolism , Mammary Neoplasms, Animal/metabolism , Extracellular Matrix Proteins/metabolism , Breast Neoplasms/pathology
5.
Photobiomodul Photomed Laser Surg ; 41(11): 644-654, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37638820

ABSTRACT

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.


Subject(s)
Dental Implants , Peri-Implantitis , Humans , Animals , Swine , Temperature , Titanium , Peri-Implantitis/radiotherapy , Surface Properties , Lasers , Fibroblasts
6.
BMC Oral Health ; 23(1): 372, 2023 06 08.
Article in English | MEDLINE | ID: mdl-37291567

ABSTRACT

OBJECTIVE: This cross-sectional study aimed to investigate socioeconomic inequalities in dental caries among adults (35 years and older) in China and explore the contributions of various factors to these inequalities. METHODS: This study included 10,983 adults (3,674 aged 35-44 years, 3,769 aged 55-64 years and 3,540 aged 65-74 years) who participated in the 4th National Oral Health Survey (2015-2016) in China. Dental caries status was evaluated by the decayed, missing and filled teeth (DMFT) index. Concentration indices (CIs) were applied to quantify the different degrees of socioeconomic-related inequality in DMFT, decayed teeth with crown or root caries (DT), missing teeth due to caries or other reasons (MT), and filled teeth without any primary or secondary caries (FT) among adults of different age groups. Decomposition analyses were conducted to identify the determinants and their associations with inequalities in DMFT. RESULTS: The significant negative CI indicated that DMFT for the total sample were concentrated among socioeconomically disadvantaged adults (CI = - 0.06; 95% confidence interval [CI], - 0.073 to - 0.047). The CIs for DMFT for adults aged 55-64 and 65-74 years were - 0.038 (95% CI, - 0.057 to - 0.018) and - 0.039 (95% CI, - 0.056 to - 0.023), respectively, while the CI for DMFT for adults aged 35-44 years was not statistically significant (CI = - 0.002; 95% CI, - 0.022 to 0.018). The concentration indices of DT were negative and concentrated in disadvantaged populations, while FT showed pro-rich inequalities in all age groups. Decomposition analyses showed that age, education level, toothbrushing frequency, income and type of insurance contributed substantially to socioeconomic inequalities, accounting for 47.9%, 29.9%, 24.5%,19.1%, and 15.3%, respectively. CONCLUSION: Dental caries was disproportionately concentrated among socioeconomically disadvantaged adults in China. The results of these decomposition analyses are informative for policy-makers attempting to develop targeted health policy recommendations to reduce dental caries inequalities in China.


Subject(s)
Dental Caries , Adult , Humans , Cross-Sectional Studies , Dental Caries/epidemiology , Dental Health Surveys , DMF Index , East Asian People , Income , Oral Health , Socioeconomic Factors , Middle Aged , Aged
7.
Exp Ther Med ; 25(6): 241, 2023 Jun.
Article in English | MEDLINE | ID: mdl-37153898

ABSTRACT

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.

8.
J Biochem Mol Toxicol ; 37(1): e23229, 2023 Jan.
Article in English | MEDLINE | ID: mdl-36184831

ABSTRACT

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.


Subject(s)
Emodin , Neuralgia , Rats , Animals , Oxaliplatin/adverse effects , NF-kappa B/metabolism , Cyclooxygenase 2 , Emodin/adverse effects , Quality of Life , Rats, Sprague-Dawley , Neuralgia/chemically induced , Neuralgia/drug therapy , Inflammation/chemically induced , Inflammation/drug therapy
9.
Mol Pain ; 18: 17448069221146398, 2022 04.
Article in English | MEDLINE | ID: mdl-36474308

ABSTRACT

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.


Subject(s)
Arthritis, Experimental , Emodin , Animals , Mice , AMP-Activated Protein Kinases/metabolism , Arthritis, Experimental/drug therapy , Arthritis, Rheumatoid , Chronic Pain , Emodin/therapeutic use , Inflammation/drug therapy , NF-E2-Related Factor 2/metabolism , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Oxidative Stress , Superoxide Dismutase/metabolism , Tumor Necrosis Factor-alpha/metabolism
10.
PLoS One ; 17(10): e0275428, 2022.
Article in English | MEDLINE | ID: mdl-36315519

ABSTRACT

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.


Subject(s)
Inflammasomes , Neuralgia , Rats , Animals , Oxaliplatin/adverse effects , Inflammasomes/metabolism , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Rats, Sprague-Dawley , Neuralgia/chemically induced , Neuralgia/drug therapy , Neuralgia/metabolism , Dynamins/metabolism , Inflammation/pathology , Mitochondria/metabolism
11.
BMC Oral Health ; 22(1): 215, 2022 05 31.
Article in English | MEDLINE | ID: mdl-35641983

ABSTRACT

BACKGROUND: The aim of this study was to assess the income-related inequality of edentulism among the aged in China and identify the contributing factors. METHODS: A secondary analysis of data from the 4th National Oral Health Epidemiology Survey in China was conducted, and 65-74 years old were selected for the analysis of income-related inequality of edentulism. The concentration curve, Concentration index (CI) and Erreygers-corrected concentration index (EI) were used to represent inequality and its degree qualitatively and quantitatively, respectively. A decomposition method based on probit model was employed to determine the contributors of inequality, including demographic factors, income status, oral health-related knowledge, attitude and practices and self-perceived general health status. RESULTS: In China, aged people with edentulism were concentrated in the poor. The CI was - 0.2337 (95% CIs: - 0.3503, - 0.1170). The EI was - 0.0413 (95% CIs: - 0.0619, - 0.0207). The decomposition results showed that income (75.02%) and oral health-related knowledge, attitude and practices (15.52%) were the main contributors to the inequality. CONCLUSION: This study showed that pro-poor inequality among the elderly with edentulism existed in China. Corresponding policies against the contributors could be considered to promote the health equality of the elders.


Subject(s)
Health Status , Income , Aged , China/epidemiology , Health Services , Humans , Socioeconomic Factors
12.
J Cell Mol Med ; 26(14): 3965-3976, 2022 07.
Article in English | MEDLINE | ID: mdl-35689386

ABSTRACT

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.


Subject(s)
Inflammation , Neoplasms , Animals , Bone and Bones , Glycogen Synthase Kinase 3 beta , Pain , Rats , Rats, Sprague-Dawley
13.
Acta Biochim Biophys Sin (Shanghai) ; 53(1): 72-84, 2021 Jan 12.
Article in English | MEDLINE | ID: mdl-33253369

ABSTRACT

Inflammatory pain activates astrocytes and increases inflammatory cytokine release in the spinal cord. Mitochondrial fusion and fission rely on the functions of dynamin-related protein 1 (Drp1) and optic atrophy 1 (OPA1), which are essential for the synaptic transmission and plasticity. In the present study, we aimed to explore the effects of 2-bromopalmitate (2-BP), an inhibitor of protein palmitoylation, on the modulation of pain behavior. Rats were intraplantar injected with complete Freund's adjuvant (CFA) to establish an inflammatory pain model. In the spinal cord of rats with CFA-induced inflammatory pain, the expression of astrocyte-specific glial fibrillary acidic protein (GFAP) and contents of proinflammatory cytokines IL-1ß and TNF-α were increased. Mitochondrial Drp1 was increased, while OPA1 was decreased. Consequently, CFA induced reactive oxygen species (ROS) production and Bcl-2-associated X protein (BAX) expression. The intrathecal administration of 2-BP significantly reversed the pain behaviors of the inflammatory pain in rats. Moreover, 2-BP also reduced the Drp1 expression, elevated the OPA1 expression, and further reduced the GFAP, IL-1ß, and TNF-α expression and ROS production. Furthermore, in vitro study proved a similar effect of 2-BP on the regulation of Drp1 and OPA1 expression. 2-BP also increased the mitochondrial membrane potential and decreased the levels of BAX, ROS, and proinflammatory cytokines. These results indicate that 2-BP may attenuate the inflammatory pain of CFA-treated rats via regulating mitochondrial fission/fusion balance and function.


Subject(s)
Anti-Inflammatory Agents/pharmacology , Mitochondrial Dynamics/drug effects , Pain/drug therapy , Palmitates/pharmacology , Animals , Anti-Inflammatory Agents/therapeutic use , Astrocytes/metabolism , Behavior, Animal/drug effects , Cell Line, Tumor , Disease Models, Animal , Dynamins/metabolism , Freund's Adjuvant/toxicity , GTP Phosphohydrolases/metabolism , Glial Fibrillary Acidic Protein/metabolism , Humans , Inflammation/chemically induced , Inflammation/drug therapy , Inflammation/metabolism , Interleukin-1beta/metabolism , Matrix Metalloproteinases/metabolism , Membrane Potential, Mitochondrial/drug effects , Oxidative Stress/drug effects , Pain/chemically induced , Pain/metabolism , Palmitates/therapeutic use , Rats, Sprague-Dawley , Reactive Oxygen Species/metabolism , Spinal Cord/metabolism , Spinal Cord/pathology , Tumor Necrosis Factor-alpha/metabolism , bcl-2-Associated X Protein/metabolism
14.
Environ Toxicol ; 36(5): 821-830, 2021 May.
Article in English | MEDLINE | ID: mdl-33336902

ABSTRACT

Dibutyl phthalate (DBP), a typical representative of phthalate esters (PAEs), is used as a plasticizer in various industrial applications and has been reported to be responsible for neurobehavioral changes. Despite mounting evidence showing that nimodipine (Nim) palys a neuropharmacological and psychopharmacological role in neurons, the attenuating effects of Nim on learning and memory impairment induced by DBP exposure remain unknown. Based on bioinformatics analysis we found that the biological processes affected by both DBP and Nim may involve the calcium signaling pathway, the MAPK signaling pathway and the apoptosis pathway. The results of an in vivo study confirmed that DBP affects the levels of Ca2+ -related proteins, up-regulates phosphorylated -ERK1/2 expression and results in hippocampal neuronal damage and apoptosis, whereas Nim as a Ca2+ antagonist, has a certain neuroprotective role to avoid these adverse effects. Our data suggest that Nim could be used to attenuate the learning and memory impairment in DBP-exposed mice, to down-regulate intracellular Ca2+ levels, subordinate the ERK1/2 pathway and attenuate apoptosis in hippocampal tissue.


Subject(s)
Dibutyl Phthalate , Nimodipine , Animals , Computational Biology , Dibutyl Phthalate/toxicity , Memory Disorders/chemically induced , Mice , Nimodipine/toxicity , Plasticizers
15.
Community Dent Oral Epidemiol ; 48(1): 32-41, 2020 02.
Article in English | MEDLINE | ID: mdl-31621099

ABSTRACT

OBJECTIVES: To explore the factors associated with utilization of oral health services among Chinese adults and older adults according to the Andersen Behavior Model. METHODS: Data from the 4th National Oral Health Survey (2015-2016) in China were used. A total of 7206 people (3669 adults aged 35-44 years and 3537 older adults aged 65-74 years) were included in our analysis. Oral health service utilization in the past 12 months was the outcome variable. Explanatory variables were selected according to the Andersen Behavior Model. Descriptive statistics and bivariate associations (chi-square tests) were analysed, followed by hierarchical Poisson regression models, which were conducted to determine the factors associated with oral health service utilization. RESULTS: In total, 21.4% (95% CI: 19.4%-23.7%) of adults (35-44 years old) and 20.7% (95% CI: 18.6%-22.9%) of older adults (65-74 years old) utilized oral health services in the past 12 months. Nearly 80% of adults (78.7%, 95% CI: 74.0%-82.7%) and more than 90% of older adults (93.7%, 95% CI: 91.0%-95.6%) visited a dentist for treatment. Adults aged 35-44 years old who were female (IRR: 1.15, 95% CI: 1.00-1.33, P = .047), had good oral health knowledge and attitudes (IRR: 1.30, 95% CI: 1.06-1.59, P = .011), perceived their oral health status as fair (IRR:1.51, 95% CI:1.24-1.85, P < .001) or poor/very poor (IRR:2.52, 95% CI:2.01-3.18, P < .001) and had a decayed, missing and filled teeth (DMFT) index >0 (IRR: 1.52, 95% CI: 1.11-2.09, P = .009) were more likely to report dental visits in the past 12 months. Older adults who utilized oral health services tended to be female (IRR: 1.32, 95% CI: 1.09-1.59, P = .004); to be covered by Urban Resident Basic Medical Insurance (URBMI) (IRR: 1.56, 95% CI: 1.18-2.05, P = .002), Urban Employee Basic Medical Insurance (UEBMI) (IRR: 1.69, 95% CI: 1.32-2.16, P < .001) or government medical insurance (GMI) (IRR: 1.03, 95% CI:1.01-2.16, P = .044); to have a high education level (IRR: 1.37, 95% CI: 1.08-1.74, P = .010); to have an income level in the 2nd tertile (IRR: 1.44, 95% CI: 1.13-1.84, P = .003) or 3rd tertile (IRR:1.52, 95% CI:1.18-1.95, P = .001); and to perceive their oral health status as poor or very poor (IRR: 1.53, 95% CI: 1.21-1.95, P = .001). CONCLUSIONS: Sex and self-perceived oral health status were associated with oral health utilization among Chinese population. Additionally, for older adults, education level, household income and insurance coverage were determinants of dental service use. These findings can aid in creating more targeted policies to increase the use of dental services by Chinese adults.


Subject(s)
Dental Care for Aged/statistics & numerical data , Dental Care , Dental Health Services/statistics & numerical data , Insurance, Health/statistics & numerical data , Oral Health , Adult , Aged , China , Dental Health Surveys , Female , Humans , Insurance Coverage , Male , Middle Aged
16.
NMR Biomed ; 32(10): e4112, 2019 10.
Article in English | MEDLINE | ID: mdl-31184789

ABSTRACT

Activated choline metabolism is a hallmark of carcinogenesis and tumor progression, which leads to elevated levels of phosphocholine and glycerophosphocholine in all types of cancer tested so far. Magnetic resonance spectroscopy applications have played a key role in detecting these elevated choline phospholipid metabolites. To date, the majority of cancer-related studies have focused on phosphocholine and the Kennedy pathway, which constitutes the biosynthesis pathway for membrane phosphatidylcholine. Fewer and more recent studies have reported on the importance of glycerophosphocholine in cancer. In this review article, we summarize the recent literature on glycerophosphocholine metabolism with respect to its cancer biology and its detection by magnetic resonance spectroscopy applications.


Subject(s)
Choline/metabolism , Glycerylphosphorylcholine/metabolism , Metabolic Networks and Pathways , Neoplasms/metabolism , Animals , Humans , Substrate Specificity , Transcription Factors/metabolism
17.
Cell Stress Chaperones ; 24(1): 247-257, 2019 01.
Article in English | MEDLINE | ID: mdl-30632065

ABSTRACT

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.


Subject(s)
Adaptation, Physiological/drug effects , Antioxidants/metabolism , Cytoprotection/drug effects , Hot Temperature , Paeonia/physiology , Photosynthesis/drug effects , Stress, Physiological/drug effects , Trehalose/pharmacology , Adaptation, Physiological/genetics , Chlorophyll/metabolism , Fluorescence , Gene Expression Regulation, Plant/drug effects , Models, Biological , Oxidative Stress/drug effects , Paeonia/drug effects , Paeonia/genetics , Plant Stomata/drug effects , Plant Stomata/physiology , Stress, Physiological/genetics
18.
Sci Rep ; 8(1): 11067, 2018 07 23.
Article in English | MEDLINE | ID: mdl-30038419

ABSTRACT

Breast cancer screening and early stage diagnosis is typically performed by X-ray mammography, which detects microcalcifications. Despite being one of the most reliable features of nonpalpable breast cancer, the processes by which these microcalcifications form are understudied and largely unknown. In the current work, we have investigated the genetic drivers for the formation of microcalcifications in breast cancer cell lines, and have investigated their involvement in disease progression. We have shown that stable silencing of the Osteopontin (OPN) gene decreased the formation of hydroxyapatite in MDA-MB-231 breast cancer cells in response to osteogenic cocktail. In addition, OPN silencing reduced breast cancer cell migration. Furthermore, breast cancer cells that had spontaneously metastasized to the lungs in a mouse model of breast cancer had largely elevated OPN levels, while circulating tumor cells in the same mouse model contained intermediately increased OPN levels as compared to parental cells. The observed dual roles of the OPN gene reveal the existence of a direct relationship between calcium deposition and the ability of breast cancer cells to metastasize to distant organs, mediated by common genetic factors.


Subject(s)
Breast Neoplasms/metabolism , Breast Neoplasms/pathology , Calcinosis/metabolism , Calcinosis/pathology , Osteopontin/metabolism , Animals , Breast Neoplasms/genetics , Calcinosis/genetics , Cell Line, Tumor , Female , Humans , Mice , Neoplasm Metastasis/genetics , Osteopontin/genetics , RNA, Small Interfering/genetics
19.
BMC Oral Health ; 18(1): 31, 2018 03 06.
Article in English | MEDLINE | ID: mdl-29510716

ABSTRACT

BACKGROUND: The utilization of oral health services in children remains at a relatively low level in China. However, little is known about the utilization patterns and related factors. The objective of this study was to explore the patterns of oral health service utilization and to determine the related factors among preschool children in Beijing, China, based on the Andersen behavioral model. METHODS: A cross-sectional study of 1425 preschool children aged 2 to 6 years was carried out in five kindergartens in Beijing, China. A questionnaire investigation of parents/caregivers was performed to collect information on oral health service utilization. Oral health needs were evaluated through oral health examinations. Chi-square tests, t-tests, multivariate logistic regression and negative binomial regression were used in this study to identify the variables associated with oral health service utilization. RESULTS: In total, 648 (45.5%) children had utilized oral health services in the past 12 months, while 24.3% had utilized preventive oral health services. Routine checkups and receiving preventive measures accounted for 63.2% of the children who utilized oral health services in the past 12 months. Children were more likely to have utilized oral health services in the past 12 months if they attended kindergartens with regular oral health care resources, if their oral health status as perceived by their parents/parents was "fair" or "poor", if they had more decayed, missing and filled teeth (dmft) and if they had experienced more dental pain. In addition, children with more dental pain and more access to oral health services, whose oral health status was perceived by parents/caregivers as worse tended to have utilized oral health services more frequently in the past 12 months. CONCLUSIONS: In conclusion, we found a strong association between access to regular oral health care resources and oral health service utilization among preschool children. Children whose oral health status was perceived by parents/caregivers as worse and who had more dental pain were more likely to have utilized oral health services in China.


Subject(s)
Dental Care for Children/statistics & numerical data , Beijing/epidemiology , Child , Child, Preschool , DMF Index , Female , Humans , Logistic Models , Male , Oral Health/statistics & numerical data
20.
Methods Mol Biol ; 1718: 331-345, 2018.
Article in English | MEDLINE | ID: mdl-29341018

ABSTRACT

Magnetic resonance spectroscopy (MRS) or spectroscopic imaging (MRSI) enables the detection of metabolites, amino acids, and lipids, among other biomolecules, in tumors of live mouse models of cancer. Tumor-bearing mice are anesthetized by breathing isoflurane in a magnetic resonance (MR) scanner dedicated to small animal MR. Here we describe the overall setup and steps for measuring 1H and 31P MRS and 1H MRSI of orthotopic breast tumor models in mice with surface coils. This protocol can be adapted to the use of volume coils to measure 1H and 31P MRS(I) of tumor models that grow inside the body. We address issues of animal handling, setting up the measurement, measurement options, and data analysis.


Subject(s)
Breast Neoplasms/pathology , Disease Models, Animal , Magnetic Resonance Imaging/methods , Magnetic Resonance Spectroscopy/methods , Animals , Breast Neoplasms/metabolism , Female , Humans , Mice , Tumor Cells, Cultured , Xenograft Model Antitumor Assays
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