Brain-computer interface(BCI)technology is rapidly advancing in medical research and application.As an emerging biomedical engineering technology,it has garnered significant attention in the clinical research of brain...Brain-computer interface(BCI)technology is rapidly advancing in medical research and application.As an emerging biomedical engineering technology,it has garnered significant attention in the clinical research of brain disease diagnosis and treatment,neurological rehabilitation,and mental health.However,BCI also raises several challenges and ethical concerns in clinical research.In this article,the authors investigate and discuss three aspects of BCI in medicine and healthcare:the state of international ethical governance,multidimensional ethical challenges pertaining to BCI in clinical research,and suggestive concerns for ethical review.Despite the great potential of frontier BCI research and development in the field of medical care,the ethical challenges induced by itself and the complexities of clinical research and brain function have put forward new special fields for ethics in BCI.To ensure"responsible innovation"in BCI research in healthcare and medicine,the creation of an ethical global governance framework and system,along with special guidelines for cutting-edge BCI research in medicine,is suggested.展开更多
Objective:To explore and understand the attitude towards dengue vaccination and its modifiable determinants among inhabitants of Aceh(northern Sumatra Island,Indonesia),the region that was most severely affected by th...Objective:To explore and understand the attitude towards dengue vaccination and its modifiable determinants among inhabitants of Aceh(northern Sumatra Island,Indonesia),the region that was most severely affected by the earthquake and tsunami of 26 December 2004.Methods:A communitybased,cross-sectional study was conducted among 535 healthy inhabitants in nine regencies(Kabupaten or Kotamadya)of Aceh that were selected randomly from November 2014 to March 2015.A set of validated,pre-tested,structured questionnaires was used to guide the interviews.The questionnaires covered a range of explanatory variables and one outcome variable(attitude to dengue vaccination).Multi-step logistic regression analysis and Spearman's rank correlation were used to test the role of explanatory variables for the outcome variable.Results:More than 70%of the participants had a poor attitude towards dengue vaccination.Modifiablc determinants associated with poor attitude to dengue vaccination were low education level,working as farmers and traditional market traders,low socioeconomic status and poor knowledge,attitude and practice regarding dengue fever(P<0.05).The KAP domain scores were correlated strongly with attitude to dengue vaccination,r_s=0.25,r_S=0.67 and r_s=0.20,respectively(P<0.001).Multivariate analysis found that independent predictors associated with attitude towards dengue vaccination among study participants were only sex and attitude towards dengue fever(P<0.001).Conclusions:This study reveals that low KAP regarding dengue fever,low education level and low socioeconomic status are associated with a poor attitude towards dengue vaccination.Therefore,inhabitants of suburbs who are working as larmers or traditional market traders with low socioeconomic status are the most appropriate target group for a dengue vaccine introduction program.展开更多
Spinal cord injury results in paralysis, sensory disturbances, sphincter dysfunction, and multiple systemic secondary conditions, most arising from autonomic dysregulation. All this produces profound negative psychoso...Spinal cord injury results in paralysis, sensory disturbances, sphincter dysfunction, and multiple systemic secondary conditions, most arising from autonomic dysregulation. All this produces profound negative psychosocial implications for affected people, their families, and their communities;the financial costs can be challenging for their families and health institutions. Treatments aimed at restoring the spinal cord after spinal cord injury, which have been tested in animal models or clinical trials, generally seek to counteract one or more of the secondary mechanisms of injury to limit the extent of the initial damage. Most published works on structural/functional restoration in acute and chronic spinal cord injury stages use a single type of treatment: a drug or trophic factor, transplant of a cell type, and implantation of a biomaterial. Despite the significant benefits reported in animal models, when translating these successful therapeutic strategies to humans, the result in clinical trials has been considered of little relevance because the improvement, when present, is usually insufficient. Until now, most studies designed to promote neuroprotection or regeneration at different stages after spinal cord injury have used single treatments. Considering the occurrence of various secondary mechanisms of injury in the acute and sub-acute phases of spinal cord injury, it is reasonable to speculate that more than one therapeutic agent could be required to promote structural and functional restoration of the damaged spinal cord. Treatments that combine several therapeutic agents, targeting different mechanisms of injury, which, when used as a single therapy, have shown some benefits, allow us to assume that they will have synergistic beneficial effects. Thus, this narrative review article aims to summarize current trends in the use of strategies that combine therapeutic agents administered simultaneously or sequentially, seeking structural and functional restoration of the injured spinal cord.展开更多
This review explores the pivotal role of circadian rhythm regulators,particularly the PER genes,in Oral Squamous Cell Carcinoma(OSCC).As key constituents of the biological clock,PERs exhibit a downregulated expression...This review explores the pivotal role of circadian rhythm regulators,particularly the PER genes,in Oral Squamous Cell Carcinoma(OSCC).As key constituents of the biological clock,PERs exhibit a downregulated expression pattern in OSCC,and the expression levels of PERs in OSCC patients are correlated with a favorable prognosis.PERs impact the occurrence and development of OSCC through multiple pathways.In the regulation of cell proliferation,they can function not only through cell cycle regultion but also via metabolic pathways.For example,PER1 can interact with receptors for activated C kinase 1(RACK1)and phosphatidylinositol 3-kinase(PI3K)through its PAS domain to inhibit glycolysis and thereby reduce cell proliferation.Regarding the regulation of cell death,PERs mediate various types of cell death in OSCC cells,such as p53-dependent apoptosis,protein kinase B(AKT)/mammalian target of rapamycin(mTOR)dependent autophagy,or hypoxia-inducible factor l-alpha(HIF-1a)mediated ferroptosis.In regulating epithelia-mesenchymal transition(EMT),PERs can lead to the downregulation of EMT related genes,such as zinc finger E-box binding homeobox 1/2(ZEBI/2),twist family BHLH transcription factor 1/2(TWIST1/2),and Vimentin,thereby influencing the migration and invasion capabilities of OSCC cells.In tumor angiogenesis,PERs exert regulatory effects on related factors,such as methionyl aminopeptidase 2(MetAP2)and vascular endothelial growth factor(VEGF).In the tumor immune microenvironment,PERs can inhibit the inhibitor of kappa B kinase(IKK)/nuclear factor kappa B(NF-kB)pathway and programmed cell death ligand 1(PD-L1)expression,thereby enhancing the cytotoxic effect of CD8+T cells on OSCC cells.In-depth studies focusing on elucidating the precise regulatory mechanisms of PERs can facilitate the development of therapeutic strategies targeting PERs,including restoration of PERs expression/activity,targeting PERs-regulated pathways,combination therapies,and chronotherapy.These furnish a theoretical foundation for formulating individualized treatment plans to achieve precise treatment for patients with OSCC.展开更多
It has been reported that ACE2 is the main host cell receptor of 2019-nCoV and plays a crucial role in the entry of virus into the cell to cause the final infection. To investigate the potential route of 2019-n Cov in...It has been reported that ACE2 is the main host cell receptor of 2019-nCoV and plays a crucial role in the entry of virus into the cell to cause the final infection. To investigate the potential route of 2019-n Cov infection on the mucosa of oral cavity, bulk RNA-seq profiles from two public databases including The Cancer Genome Atlas(TCGA) and Functional Annotation of The Mammalian Genome Cap Analysis of Gene Expression(FANTOM5 CAGE) dataset were collected. RNA-seq profiling data of 13 organ types with para-carcinoma normal tissues from TCGA and 14 organ types with normal tissues from FANTOM5 CAGE were analyzed in order to explore and validate the expression of ACE2 on the mucosa of oral cavity. Further, single-cell transcriptomes from an independent data generated in-house were used to identify and confirm the ACE2-expressing cell composition and proportion in oral cavity. The results demonstrated that the ACE2 expressed on the mucosa of oral cavity. Interestingly, this receptor was highly enriched in epithelial cells of tongue. Preliminarily, those findings have explained the basic mechanism that the oral cavity is a potentially high risk for 2019-nCoV infectious susceptibility and provided a piece of evidence for the future prevention strategy in dental clinical practice as well as daily life.展开更多
With recent developments in photosensitizers and light delivery systems,topical 5-aminolevulinic acid-mediated photodynamic therapy (ALA-PDT) has become the fourth alternative therapeutic approach in the management of...With recent developments in photosensitizers and light delivery systems,topical 5-aminolevulinic acid-mediated photodynamic therapy (ALA-PDT) has become the fourth alternative therapeutic approach in the management of oral leucoplakia (OLK) due to its minimally invasive nature,efficacy,and low risk of systemic side effects and disfigurement.This report presents step-by-step guidelines for applying topical ALA-PDT in the management of OLK based on both the clinical experience of the authors and a systematic review of the current literature.Studies using protocols with standardized parameters and randomized clinical trials at multiple centres with adequate sample sizes and both interim and long-term follow-ups are needed before universally applicable guidelines can be produced in this field.展开更多
Periodontitis is an inflammatory disease involving the destruction of both soft and hard tissue in the periodontal region.Although dysbiosis of the local microbial community initiates local inflammation,over-activatio...Periodontitis is an inflammatory disease involving the destruction of both soft and hard tissue in the periodontal region.Although dysbiosis of the local microbial community initiates local inflammation,over-activation of the host immune response directly activates osteoclastic activity and alveolar bone loss.Many studies have reported on the cytokine network involved in periodontitis and its crucial and pleiotropic effect on the recruitment of specific immunocytes,control of pathobionts and induction or suppression of osteoclastic activity.Nonetheless,particularities in the stimulation of pathogens in the oral cavity that lead to the specific and complex periodontal cytokine network are far from clarified.Thus,in this review,we begin with an up-to-date aetiological hypothesis of periodontal disease and summarize the roles of cytokines in the host immune response.In addition,we also summarize the latest cytokine-related therapeutic measures for periodontal disease.展开更多
Investigations into the inheritance of the three risk alleles R702W, G908R and 1007 fsInsC in NOD2 associated with susceptibility to Crohn＇s disease have demonstrated a remarkable amount of heterogeneity across ethni...Investigations into the inheritance of the three risk alleles R702W, G908R and 1007 fsInsC in NOD2 associated with susceptibility to Crohn＇s disease have demonstrated a remarkable amount of heterogeneity across ethnicities and populations, with regional variation across Europe for example, suggesting local founder effects. In nonCaucasian populations Crohn＇s disease continues to increase in incidence but this increase appears not to be a consequence of variation in NOD2, further advancing the accumulating evidence for other susceptibility loci. Frequencies of the known alleles are compared across populations in health and disease and evidence for additional alleles in NOD2 is reviewed. Based on its position on chromosome 16 coincident with some other autoimmune disease susceptibility Iocalizations, research has targeted NOD2 variation as the potential cause of other autoimmune disorders. While these investigations have mostly returned negative findings, two diseases, Blau Syndrome and Graft versus Host Disease, have been shown to be caused by risk alleles in NOD2. As is frequent in complex disease investigations, some results await validation, but the identification of NOD2 and the differences within and across population raises intriguing questions about the population genetics of the variation at this locus.展开更多
Objective This study aimed to assess the risk of cumulative exposure to Pb,Cd,Hg,and iAs through aquatic products consumed by Chinese people.Methods Heavy metal concentration data were obtained from the national food ...Objective This study aimed to assess the risk of cumulative exposure to Pb,Cd,Hg,and iAs through aquatic products consumed by Chinese people.Methods Heavy metal concentration data were obtained from the national food contamination monitoring program during 2013–2017.Consumption data were derived from the China National Food Consumption Survey in 2014 and the relative potency factor(RPF)method was used to estimate cumulative exposure for neurotoxicity and nephrotoxicity.Results The results demonstrated that the cumulative exposure based on neurotoxicity was below the lower confidence limit on benchmark doses of lead(BMDL01)for nephrotoxicity and the cumulative exposures were all lower than the provisional tolerable monthly intake(PTMI)of Cd.However,the margin of exposure values(MOEs)of the cumulative exposures for neurotoxicity in the 2–6 year-old group was close to 1 and the cumulative exposure level for nephrotoxicity accounted for 90.21%of the PTMI.Conclusion The cumulative exposures of the 2–6 year-old group to the four heavy metals did not reach(but came close to)the corresponding safety threshold for both neurotoxicity and nephrotoxicity.Given that there are still other food sources of these four heavy metals,it is necessary to more closely study their cumulative health effects.展开更多
Gap junction(GJ)has been indicated to have an intimate correlation with adhesion junction.However,the direct interaction between them partially remains elusive.In the current study,we aimed to elucidate the role of N-...Gap junction(GJ)has been indicated to have an intimate correlation with adhesion junction.However,the direct interaction between them partially remains elusive.In the current study,we aimed to elucidate the role of N-cadherin,one of the core components in adhesion junction,in mediating connexin 43,one of the functional constituents in gap junction,via transforming growth factor-β1(TGF-β1)induction in osteoblasts.We first elucidated the expressions of N-cadherin induced by TGF-β1 and also confirmed the upregulation of Cx43,and the enhancement of functional gap junctional intercellular communication(GJIC)triggered by TGF-β1 in both primary osteoblasts and MC3T3 cell line.Colocalization analysis and Co-IP experimentation showed that N-cadherin interacts with Cx43 at the site of cell–cell contact.Knockdown of N-cadherin by siRNA interference decreased the Cx43 expression and abolished the promoting effect of TGF-β1 on Cx43.Functional GJICs in living primary osteoblasts and MC3T3 cell line were also reduced.TGF-β1-induced increase in N-cadherin and Cx43 was via Smad3 activation,whereas knockdown of Smad3 signaling by using siRNA decreased the expressions of both N-cadherin and Cx43.Overall,these data indicate the direct interactions between N-cadherin and Cx43,and reveal the intervention of adhesion junction in functional gap junction in living osteoblasts.展开更多
The lineage specification of mesenchymal stem/stromal cells(MSCs) is tightly regulated by a wide range of factors. Recently, the versatile functions of ZBP1(also known as DAI or DLM-1) have been reported in the blood ...The lineage specification of mesenchymal stem/stromal cells(MSCs) is tightly regulated by a wide range of factors. Recently, the versatile functions of ZBP1(also known as DAI or DLM-1) have been reported in the blood circulation and immune systems.However, the biological function of ZBP1 during the lineage specification of MSCs is still unknown. In the present study, we found that ZBP1 was upregulated during osteogenesis but downregulated during adipogenesis in mouse bone marrow-derived MSCs(m BMSCs). ZBP1 was highly expressed in osteoblasts but expressed at a relatively low level in marrow adipocytes. Knockdown of ZBP1 inhibited alkaline phosphataseactivity, extracellular matrix mineralization, and osteogenesis-related gene expression in vitro and reduced ectopic bone formation in vivo. Knockdown of ZBP1 also promoted adipogenesis in MSCs in vitro. Conversely, the overexpression of ZBP1 increased the osteogenesis but suppressed the adipogenesis of MSCs. When the expression of ZBP1 was rescued, the osteogenic capacity of ZBP1-depleted m BMSCs was restored at both the molecular and phenotypic levels.Furthermore, we demonstrated that ZBP1, a newly identified target of Wnt/β-catenin signaling, was required for β-catenin translocation into nuclei. Collectively, our results indicate that ZBP1 is a novel regulator of bone and fat transdifferentiation via Wnt/β-catenin signaling.展开更多
Objective:To develop a rapid,cost effective RT-PCR method for the mass scale diagnosis of such diseases at the vireraia stage to find out the actual disease burden in that area.Methods:For this purpose,cases with the ...Objective:To develop a rapid,cost effective RT-PCR method for the mass scale diagnosis of such diseases at the vireraia stage to find out the actual disease burden in that area.Methods:For this purpose,cases with the history of only short febrile illness were considered.Thus 157 samples with the history of dengue/chikungunya like illness and only 58 samples with a history of acute encephalitis syndrome(AES)were selected.Results:Out of 157 samples,42 and 74 were detected as dengue and chikungunya,respectively and out of 58 AES cases only 23 could be detected as Japanese encephalitis by this RT-PCR method.Conclusions:This cost effective RT-PCR method can detect the total positive cases that remain undetected by EL1SA method.Moreover,this method is capable to detect the viral RNA from patients'sera even after the appearance of IgM antibody at one fifth costs as compared with the other commercially available kits.展开更多
Objective The present study was undertaken to evaluate the subchronic oral toxicity of sodium dehydroacetate(DHA-Na)and to determine the point of departure(POD),which is a critical factor in the establishment of an ac...Objective The present study was undertaken to evaluate the subchronic oral toxicity of sodium dehydroacetate(DHA-Na)and to determine the point of departure(POD),which is a critical factor in the establishment of an acceptable dietary intake.Methods DHA-Na was administered once daily by gavage to Sprague–Dawley rats at dose levels of 0.0,31.0,62.0,and 124.0 mg/kg BW per day for 90 days,followed by a recovery period of 4 weeks in the control and 124.0 mg/kg BW per day groups.The outcome parameters were mortality,clinical observations,body weights,food consumption,hematology and clinical biochemistry,endocrine hormone levels,and ophthalmic,urinary,and histopathologic indicators.The benchmark dose(BMD)approach was applied to estimate the POD.Results Significant decreases were found in the 62.0 and 124.0 mg/kg BW groups in terms of the body weight and food utilization rate,whereas a significant increase was found in the thyroid stimulating hormone levels of the 124.0 mg/kg BW group.Importantly,the 95%lower confidence limit on the BMD of 51.7 mg/kg BW was modeled for a reduction in body weight.Conclusion The repeated-dose study indicated the slight systemic toxicity of DHA-Na at certain levels(62.0 and 124.0 mg/kg BW)after a 90-day oral exposure.展开更多
AIM： To determine the HLA-DQ locus in Mexican patients with Chronic gastritis and gastric adenocarcinoma.METHODS： Oligotyping for HLA-DQ locus was performed in 45 Mexican patients with chronic gastritis and 13 Mexic...AIM： To determine the HLA-DQ locus in Mexican patients with Chronic gastritis and gastric adenocarcinoma.METHODS： Oligotyping for HLA-DQ locus was performed in 45 Mexican patients with chronic gastritis and 13 Mexican patients with diffuse-type gastric adenocarcinoma, and was then compared with 99 clinically healthy unrelated individuals. H pylori infection and CagA status were assessed in patients by enzyme-linked immunosorbent assay （EUSA） method. RESULTS： We found a significant increased frequency of HLA-DQBI＊0401 allele in Hpylori-positive patients with chronic gastritis when compared with healthy subjects [19 vs 0%, P = 1 × 10^-7, odds ratio （OR） = 4.96; 95% confidence interval （95% CI）, 3.87-6.35]. We also found a significant increased frequency of HLA-DQBI＊0501 in patients with diffuse-type gastric carcinoma in comparison with healthy individuals （P = 1 × 10^4, OR = 13.07; 95% CI, 2.82-85.14）.CONCLUSION： HLA-DQ locus may play a different role in the development of H pylori-related chronic gastritis and difffuse-type gastric adenocarcinoma in the Mexican Mestizo population.展开更多
AIM:To investigate lipid metabolism and the relationship with monocyte expression of the fatty acid translocase CD36 in South Asians.METHODS:An observational study of South Asians whom as an ethnic group have-a higher...AIM:To investigate lipid metabolism and the relationship with monocyte expression of the fatty acid translocase CD36 in South Asians.METHODS:An observational study of South Asians whom as an ethnic group have-a higher risk of developing diabetes.The susceptibility to diabetes is coupled with an earlier and more rapid progression of micro-,and macro-vascular complications.Twentynine healthy South Asian participants [mean age 34.6(8.9) years,76.2% male,mean body-mass index 25.0(5.2) kg/m2] were recruited from an urban residential area of central Birmingham(United Kingdom).The main outcomes measured were post prandial(30 min) and post absorptive(120 min) changes from fasting(0 min) in circulating lipoproteins,lipds and hormones,andmonocyte expression of CD36 post injection of a 75 g oral glucose challenge.The inducements of variations of monocyte CD36 expression were analysed.RESULTS:Our results showed evident changes in monocyte CD36 expression following the glucose challenge(P < 0.001).Non-esterified fatty acids(NEFA) levels decreased progressively during the challenge(P < 0.001),in contrast to increased cholesterol(but not triglyceride) concentrations within very low density lipoprotein(VLDL) and low density lipoprotein subfractions(P < 0.01).Levels of,glucose,serum triglycerides and high density lipoprotein cholesterol remained largely unchanged.Variations of monocyte CD36 were negatively(r =-0.47,P = 0.04) associated to fat from the diet and positively to carbohydrate from the diet(r = 0.65,P < 0.001).CONCLUSION:These data suggest that the initiation of VLDL genesis follows the consumption of glucose within this population,inferring that the sequestration of NEFA from these particles happens due to the increased availability of CD36 receptors.While these are preliminary results,it would appear that lifestyle exposures have a role in moderating the expression of CD36.展开更多
Objective:To assess the role of polymerase chain reaction(PCR)in serum sauples,in the diagnosis of osteoarticular tuberculosis(OTB)in a setting where only clinical and imaging diagnoses determine the treatment.Methods...Objective:To assess the role of polymerase chain reaction(PCR)in serum sauples,in the diagnosis of osteoarticular tuberculosis(OTB)in a setting where only clinical and imaging diagnoses determine the treatment.Methods:A total of 44 consecutive serum specimens were collected from clinically suspected OTB patients,based on clinical and radiological[X-ray or magnetic resonance imagng/computecl tomography]features.They were scrcened by in-house nested PCR.In addition,a few specimens were examined by Gram stain,acid-fast bacilli stain,histand routine bacterial culture.A total of 39 specimens were collected from patients suffering from other bone diseases of nontuberculous origin and included as negative controls.Results:of the 44 clinically suspected OTB patients,in-house nested PCR was positive in 40(91%)cases;PCR was negative in 38(97%)negative controls.Sensitivity and specificity of our in—house nested PCR was 90.3%and 97.4%,respectively.The PCR report was available within 48 h.It was possible to standardize serum PCR technique and in positive cases,a good n was observed in terms of an adequate treatment response.Conclusions:Nested PCR in serum samples is a rapid,highly sensitive and specific modality for OTB detection,PCR should be performed in addition to clinical evaluation,imaging studies,acidfast bacilli staining,culture and histopathology diagnosis,if possible.展开更多
AIM: To establish a link between the risk of diabetes with haemoglobinopathies by examining available evidence of the effects of iron and blood glucose homeostasis from molecular to epidemiological perspectives.METHOD...AIM: To establish a link between the risk of diabetes with haemoglobinopathies by examining available evidence of the effects of iron and blood glucose homeostasis from molecular to epidemiological perspectives.METHODS: A systematic literature search was performed using electronic literature databases using various search terms. The International Diabetes Federation World Atlas was used to generate a list of populations with high rates of diabetes. Pub Med, Scopus and Google Scholar were used to identify which of these populations also had a reported prevalence of haemoglobin abnormalities.RESULTS: Abnormalities in iron homeostasis leads to increases in reactive oxygen species in the blood. This promotes oxidative stress which contributes to peripheral resistance to insulin in two ways:(1) reduced insulin/insulin receptor interaction; and(2) β-cell dysfunction. Hepcidin is crucial in terms of maintaining appropriate amounts of iron in the body and is in turn affected by haemoglobinopathies. Hepcidin also has other metabolic effects in places such as the liver but so far the extent of these is not well understood. It does however directly control the levels of serum ferritin. High serum ferritin is found in obese patients and those with diabetes and a meta-analysis of the various studies shows that high serum ferritin does indeed increase diabetes risk.CONCLUSION: From an epidemiological standpoint, it is plausible that the well-documented protective effects of haemoglobinopathies with regard to malaria may have also offered other evolutionary advantages. By contributing to peripheral insulin resistance, haemoglobinopathies may have helped to sculpt the so-called "thrifty genotype", which hypothetically is advantageous in times of famine. The prevalence data however is not extensive enough to provide concrete associations between diabetes and haemoglobinopathies- more precise studies are required.展开更多
Oral squamous cell carcinoma(OSCC)become a heavy burden of public health,with approximately 300000 newly diagnosed cases and 145000 deaths worldwide per year.Nucleotide metabolism fuel DNA replication and RNA synthesi...Oral squamous cell carcinoma(OSCC)become a heavy burden of public health,with approximately 300000 newly diagnosed cases and 145000 deaths worldwide per year.Nucleotide metabolism fuel DNA replication and RNA synthesis,which is indispensable for cell proliferation.But how tumor cells orchestrate nucleotide metabolic enzymes to support their rapid growth is largely unknown.Here we show that expression of pyrimidine metabolic enzyme dihydroorotate dehydrogenase(DHODH)is upregulated in OSCC tissues,compared to non-cancerous adjacent tissues.Enhanced expression of DHODH is correlated with a shortened patient survival time.Inhibition of DHODH by either shRNA or selective inhibitors impairs proliferation of OSCC cells and growth of tumor xenograft.Further,loss of functional DHODH imped de novo pyrimidine synthesis,and disrupt mitochondrial respiration probably through destabilizing the MICOS complex.Mechanistic study shows that transcriptional factor SOX2 plays an important role in the upregulation of DHODH in OSCC.Our findings add to the knowledge of how cancer cells co-opt nucleotide metabolism to support their rapid growth,and thereby highlight DHODH as a potential prognostic and therapeutic target for OSCC treatment.展开更多
Oral squamous cell carcinoma(OSCC)is one of the most common cancers worldwide,and with 354864 new cases each year.Cancer metastasis,recurrence,and drug resistance are the main causes to cripples and deaths of OSCC pat...Oral squamous cell carcinoma(OSCC)is one of the most common cancers worldwide,and with 354864 new cases each year.Cancer metastasis,recurrence,and drug resistance are the main causes to cripples and deaths of OSCC patients.As potent growth factors,fibroblast growth factors(FGFs)are frequently susceptible to being hijacked by cancer cells.In this study,we show that FGF8 is upregulated in OSCC tissues and high FGF8 expression is related with a set of clinicopathologic parameters,including age,drinking,and survival time.FGF8 treatment enhances the invasive capability of OSCC cells.Lentivirus-based FGF8 expression promotes OSCC metastasis in a mouse lung metastasis model.Further,mechanistic study demonstrates that FGF8 induces epithelial–mesenchymal transition(EMT)in OSCC cells.These results highlight a pro-metastatic function of FGF8,and underscore the role of FGF8 in OSCC development.展开更多
基金supported by the Ministry of Science and Tech-nology of the People's Republic of China(2021ZD0201900),Project 5(2021ZD0201905).
文摘Brain-computer interface(BCI)technology is rapidly advancing in medical research and application.As an emerging biomedical engineering technology,it has garnered significant attention in the clinical research of brain disease diagnosis and treatment,neurological rehabilitation,and mental health.However,BCI also raises several challenges and ethical concerns in clinical research.In this article,the authors investigate and discuss three aspects of BCI in medicine and healthcare:the state of international ethical governance,multidimensional ethical challenges pertaining to BCI in clinical research,and suggestive concerns for ethical review.Despite the great potential of frontier BCI research and development in the field of medical care,the ethical challenges induced by itself and the complexities of clinical research and brain function have put forward new special fields for ethics in BCI.To ensure"responsible innovation"in BCI research in healthcare and medicine,the creation of an ethical global governance framework and system,along with special guidelines for cutting-edge BCI research in medicine,is suggested.
文摘Objective:To explore and understand the attitude towards dengue vaccination and its modifiable determinants among inhabitants of Aceh(northern Sumatra Island,Indonesia),the region that was most severely affected by the earthquake and tsunami of 26 December 2004.Methods:A communitybased,cross-sectional study was conducted among 535 healthy inhabitants in nine regencies(Kabupaten or Kotamadya)of Aceh that were selected randomly from November 2014 to March 2015.A set of validated,pre-tested,structured questionnaires was used to guide the interviews.The questionnaires covered a range of explanatory variables and one outcome variable(attitude to dengue vaccination).Multi-step logistic regression analysis and Spearman's rank correlation were used to test the role of explanatory variables for the outcome variable.Results:More than 70%of the participants had a poor attitude towards dengue vaccination.Modifiablc determinants associated with poor attitude to dengue vaccination were low education level,working as farmers and traditional market traders,low socioeconomic status and poor knowledge,attitude and practice regarding dengue fever(P<0.05).The KAP domain scores were correlated strongly with attitude to dengue vaccination,r_s=0.25,r_S=0.67 and r_s=0.20,respectively(P<0.001).Multivariate analysis found that independent predictors associated with attitude towards dengue vaccination among study participants were only sex and attitude towards dengue fever(P<0.001).Conclusions:This study reveals that low KAP regarding dengue fever,low education level and low socioeconomic status are associated with a poor attitude towards dengue vaccination.Therefore,inhabitants of suburbs who are working as larmers or traditional market traders with low socioeconomic status are the most appropriate target group for a dengue vaccine introduction program.
文摘Spinal cord injury results in paralysis, sensory disturbances, sphincter dysfunction, and multiple systemic secondary conditions, most arising from autonomic dysregulation. All this produces profound negative psychosocial implications for affected people, their families, and their communities;the financial costs can be challenging for their families and health institutions. Treatments aimed at restoring the spinal cord after spinal cord injury, which have been tested in animal models or clinical trials, generally seek to counteract one or more of the secondary mechanisms of injury to limit the extent of the initial damage. Most published works on structural/functional restoration in acute and chronic spinal cord injury stages use a single type of treatment: a drug or trophic factor, transplant of a cell type, and implantation of a biomaterial. Despite the significant benefits reported in animal models, when translating these successful therapeutic strategies to humans, the result in clinical trials has been considered of little relevance because the improvement, when present, is usually insufficient. Until now, most studies designed to promote neuroprotection or regeneration at different stages after spinal cord injury have used single treatments. Considering the occurrence of various secondary mechanisms of injury in the acute and sub-acute phases of spinal cord injury, it is reasonable to speculate that more than one therapeutic agent could be required to promote structural and functional restoration of the damaged spinal cord. Treatments that combine several therapeutic agents, targeting different mechanisms of injury, which, when used as a single therapy, have shown some benefits, allow us to assume that they will have synergistic beneficial effects. Thus, this narrative review article aims to summarize current trends in the use of strategies that combine therapeutic agents administered simultaneously or sequentially, seeking structural and functional restoration of the injured spinal cord.
基金supported by the following funding:National Natural Science Foundations of China(82002888,82272899 and 82370974)Sichuan Science and Technology Program(2022YFS0207 and 2023YFS0127)+1 种基金Scientific Research Foundation,WestChinaHospital of Stomatology SichuanUniversity(RCDWJS2021-8)the CAMS Innovation Fund for Medical Sciences(CIFMS,2019-I2M-5-004).
文摘This review explores the pivotal role of circadian rhythm regulators,particularly the PER genes,in Oral Squamous Cell Carcinoma(OSCC).As key constituents of the biological clock,PERs exhibit a downregulated expression pattern in OSCC,and the expression levels of PERs in OSCC patients are correlated with a favorable prognosis.PERs impact the occurrence and development of OSCC through multiple pathways.In the regulation of cell proliferation,they can function not only through cell cycle regultion but also via metabolic pathways.For example,PER1 can interact with receptors for activated C kinase 1(RACK1)and phosphatidylinositol 3-kinase(PI3K)through its PAS domain to inhibit glycolysis and thereby reduce cell proliferation.Regarding the regulation of cell death,PERs mediate various types of cell death in OSCC cells,such as p53-dependent apoptosis,protein kinase B(AKT)/mammalian target of rapamycin(mTOR)dependent autophagy,or hypoxia-inducible factor l-alpha(HIF-1a)mediated ferroptosis.In regulating epithelia-mesenchymal transition(EMT),PERs can lead to the downregulation of EMT related genes,such as zinc finger E-box binding homeobox 1/2(ZEBI/2),twist family BHLH transcription factor 1/2(TWIST1/2),and Vimentin,thereby influencing the migration and invasion capabilities of OSCC cells.In tumor angiogenesis,PERs exert regulatory effects on related factors,such as methionyl aminopeptidase 2(MetAP2)and vascular endothelial growth factor(VEGF).In the tumor immune microenvironment,PERs can inhibit the inhibitor of kappa B kinase(IKK)/nuclear factor kappa B(NF-kB)pathway and programmed cell death ligand 1(PD-L1)expression,thereby enhancing the cytotoxic effect of CD8+T cells on OSCC cells.In-depth studies focusing on elucidating the precise regulatory mechanisms of PERs can facilitate the development of therapeutic strategies targeting PERs,including restoration of PERs expression/activity,targeting PERs-regulated pathways,combination therapies,and chronotherapy.These furnish a theoretical foundation for formulating individualized treatment plans to achieve precise treatment for patients with OSCC.
基金This study was supported by grants from the National Natural Science Foundation of China(81520108009,81991502,81771081,and 81991500)the 111 Project of MOE(B14038),China.
文摘It has been reported that ACE2 is the main host cell receptor of 2019-nCoV and plays a crucial role in the entry of virus into the cell to cause the final infection. To investigate the potential route of 2019-n Cov infection on the mucosa of oral cavity, bulk RNA-seq profiles from two public databases including The Cancer Genome Atlas(TCGA) and Functional Annotation of The Mammalian Genome Cap Analysis of Gene Expression(FANTOM5 CAGE) dataset were collected. RNA-seq profiling data of 13 organ types with para-carcinoma normal tissues from TCGA and 14 organ types with normal tissues from FANTOM5 CAGE were analyzed in order to explore and validate the expression of ACE2 on the mucosa of oral cavity. Further, single-cell transcriptomes from an independent data generated in-house were used to identify and confirm the ACE2-expressing cell composition and proportion in oral cavity. The results demonstrated that the ACE2 expressed on the mucosa of oral cavity. Interestingly, this receptor was highly enriched in epithelial cells of tongue. Preliminarily, those findings have explained the basic mechanism that the oral cavity is a potentially high risk for 2019-nCoV infectious susceptibility and provided a piece of evidence for the future prevention strategy in dental clinical practice as well as daily life.
基金supported by grants from the National Natural Science Foundation of China (81572663, 81621062, 81730030, 81771081 and 81520108009)the 111 Project of MOE (B14038), Chinathe National Health Planning Commission of China (201502018)
文摘With recent developments in photosensitizers and light delivery systems,topical 5-aminolevulinic acid-mediated photodynamic therapy (ALA-PDT) has become the fourth alternative therapeutic approach in the management of oral leucoplakia (OLK) due to its minimally invasive nature,efficacy,and low risk of systemic side effects and disfigurement.This report presents step-by-step guidelines for applying topical ALA-PDT in the management of OLK based on both the clinical experience of the authors and a systematic review of the current literature.Studies using protocols with standardized parameters and randomized clinical trials at multiple centres with adequate sample sizes and both interim and long-term follow-ups are needed before universally applicable guidelines can be produced in this field.
基金supported by the National Natural Science Foundation of China(grant numbers:81621062 and 81730030)
文摘Periodontitis is an inflammatory disease involving the destruction of both soft and hard tissue in the periodontal region.Although dysbiosis of the local microbial community initiates local inflammation,over-activation of the host immune response directly activates osteoclastic activity and alveolar bone loss.Many studies have reported on the cytokine network involved in periodontitis and its crucial and pleiotropic effect on the recruitment of specific immunocytes,control of pathobionts and induction or suppression of osteoclastic activity.Nonetheless,particularities in the stimulation of pathogens in the oral cavity that lead to the specific and complex periodontal cytokine network are far from clarified.Thus,in this review,we begin with an up-to-date aetiological hypothesis of periodontal disease and summarize the roles of cytokines in the host immune response.In addition,we also summarize the latest cytokine-related therapeutic measures for periodontal disease.
基金Supported by National Health andMedical Research Council,Australia
文摘Investigations into the inheritance of the three risk alleles R702W, G908R and 1007 fsInsC in NOD2 associated with susceptibility to Crohn＇s disease have demonstrated a remarkable amount of heterogeneity across ethnicities and populations, with regional variation across Europe for example, suggesting local founder effects. In nonCaucasian populations Crohn＇s disease continues to increase in incidence but this increase appears not to be a consequence of variation in NOD2, further advancing the accumulating evidence for other susceptibility loci. Frequencies of the known alleles are compared across populations in health and disease and evidence for additional alleles in NOD2 is reviewed. Based on its position on chromosome 16 coincident with some other autoimmune disease susceptibility Iocalizations, research has targeted NOD2 variation as the potential cause of other autoimmune disorders. While these investigations have mostly returned negative findings, two diseases, Blau Syndrome and Graft versus Host Disease, have been shown to be caused by risk alleles in NOD2. As is frequent in complex disease investigations, some results await validation, but the identification of NOD2 and the differences within and across population raises intriguing questions about the population genetics of the variation at this locus.
基金the Min istry of Scie nee and Tech no logy of the People's Republic of China[No.2018YFC1603104]Chinese Academy of Medical Science Research Unit Program[NO.2019-12M-5-024].
文摘Objective This study aimed to assess the risk of cumulative exposure to Pb,Cd,Hg,and iAs through aquatic products consumed by Chinese people.Methods Heavy metal concentration data were obtained from the national food contamination monitoring program during 2013–2017.Consumption data were derived from the China National Food Consumption Survey in 2014 and the relative potency factor(RPF)method was used to estimate cumulative exposure for neurotoxicity and nephrotoxicity.Results The results demonstrated that the cumulative exposure based on neurotoxicity was below the lower confidence limit on benchmark doses of lead(BMDL01)for nephrotoxicity and the cumulative exposures were all lower than the provisional tolerable monthly intake(PTMI)of Cd.However,the margin of exposure values(MOEs)of the cumulative exposures for neurotoxicity in the 2–6 year-old group was close to 1 and the cumulative exposure level for nephrotoxicity accounted for 90.21%of the PTMI.Conclusion The cumulative exposures of the 2–6 year-old group to the four heavy metals did not reach(but came close to)the corresponding safety threshold for both neurotoxicity and nephrotoxicity.Given that there are still other food sources of these four heavy metals,it is necessary to more closely study their cumulative health effects.
文摘Gap junction(GJ)has been indicated to have an intimate correlation with adhesion junction.However,the direct interaction between them partially remains elusive.In the current study,we aimed to elucidate the role of N-cadherin,one of the core components in adhesion junction,in mediating connexin 43,one of the functional constituents in gap junction,via transforming growth factor-β1(TGF-β1)induction in osteoblasts.We first elucidated the expressions of N-cadherin induced by TGF-β1 and also confirmed the upregulation of Cx43,and the enhancement of functional gap junctional intercellular communication(GJIC)triggered by TGF-β1 in both primary osteoblasts and MC3T3 cell line.Colocalization analysis and Co-IP experimentation showed that N-cadherin interacts with Cx43 at the site of cell–cell contact.Knockdown of N-cadherin by siRNA interference decreased the Cx43 expression and abolished the promoting effect of TGF-β1 on Cx43.Functional GJICs in living primary osteoblasts and MC3T3 cell line were also reduced.TGF-β1-induced increase in N-cadherin and Cx43 was via Smad3 activation,whereas knockdown of Smad3 signaling by using siRNA decreased the expressions of both N-cadherin and Cx43.Overall,these data indicate the direct interactions between N-cadherin and Cx43,and reveal the intervention of adhesion junction in functional gap junction in living osteoblasts.
基金supported by the Foundation of the National Natural Science Foundation of China (No. 81671024, 81371171, 81571009, and 81600877)the China Postdoctoral Science Foundation (2016M600745)。
文摘The lineage specification of mesenchymal stem/stromal cells(MSCs) is tightly regulated by a wide range of factors. Recently, the versatile functions of ZBP1(also known as DAI or DLM-1) have been reported in the blood circulation and immune systems.However, the biological function of ZBP1 during the lineage specification of MSCs is still unknown. In the present study, we found that ZBP1 was upregulated during osteogenesis but downregulated during adipogenesis in mouse bone marrow-derived MSCs(m BMSCs). ZBP1 was highly expressed in osteoblasts but expressed at a relatively low level in marrow adipocytes. Knockdown of ZBP1 inhibited alkaline phosphataseactivity, extracellular matrix mineralization, and osteogenesis-related gene expression in vitro and reduced ectopic bone formation in vivo. Knockdown of ZBP1 also promoted adipogenesis in MSCs in vitro. Conversely, the overexpression of ZBP1 increased the osteogenesis but suppressed the adipogenesis of MSCs. When the expression of ZBP1 was rescued, the osteogenic capacity of ZBP1-depleted m BMSCs was restored at both the molecular and phenotypic levels.Furthermore, we demonstrated that ZBP1, a newly identified target of Wnt/β-catenin signaling, was required for β-catenin translocation into nuclei. Collectively, our results indicate that ZBP1 is a novel regulator of bone and fat transdifferentiation via Wnt/β-catenin signaling.
基金supported by the Department of Science and Technology,Goverment of West Bengal.India[grant No.705(Sanc.)ST/P/S&T/9G-27/2007]
文摘Objective:To develop a rapid,cost effective RT-PCR method for the mass scale diagnosis of such diseases at the vireraia stage to find out the actual disease burden in that area.Methods:For this purpose,cases with the history of only short febrile illness were considered.Thus 157 samples with the history of dengue/chikungunya like illness and only 58 samples with a history of acute encephalitis syndrome(AES)were selected.Results:Out of 157 samples,42 and 74 were detected as dengue and chikungunya,respectively and out of 58 AES cases only 23 could be detected as Japanese encephalitis by this RT-PCR method.Conclusions:This cost effective RT-PCR method can detect the total positive cases that remain undetected by EL1SA method.Moreover,this method is capable to detect the viral RNA from patients'sera even after the appearance of IgM antibody at one fifth costs as compared with the other commercially available kits.
基金supported by the National Key R&D Program of China[2019YFC1605203]China Food Safety Talent Competency Development Initiative:CFSA 523 Program
文摘Objective The present study was undertaken to evaluate the subchronic oral toxicity of sodium dehydroacetate(DHA-Na)and to determine the point of departure(POD),which is a critical factor in the establishment of an acceptable dietary intake.Methods DHA-Na was administered once daily by gavage to Sprague–Dawley rats at dose levels of 0.0,31.0,62.0,and 124.0 mg/kg BW per day for 90 days,followed by a recovery period of 4 weeks in the control and 124.0 mg/kg BW per day groups.The outcome parameters were mortality,clinical observations,body weights,food consumption,hematology and clinical biochemistry,endocrine hormone levels,and ophthalmic,urinary,and histopathologic indicators.The benchmark dose(BMD)approach was applied to estimate the POD.Results Significant decreases were found in the 62.0 and 124.0 mg/kg BW groups in terms of the body weight and food utilization rate,whereas a significant increase was found in the thyroid stimulating hormone levels of the 124.0 mg/kg BW group.Importantly,the 95%lower confidence limit on the BMD of 51.7 mg/kg BW was modeled for a reduction in body weight.Conclusion The repeated-dose study indicated the slight systemic toxicity of DHA-Na at certain levels(62.0 and 124.0 mg/kg BW)after a 90-day oral exposure.
基金Supported in part by Consejo Nacional de Ciencia y Tecnologiagrant, Mexico, No. 153237
文摘AIM： To determine the HLA-DQ locus in Mexican patients with Chronic gastritis and gastric adenocarcinoma.METHODS： Oligotyping for HLA-DQ locus was performed in 45 Mexican patients with chronic gastritis and 13 Mexican patients with diffuse-type gastric adenocarcinoma, and was then compared with 99 clinically healthy unrelated individuals. H pylori infection and CagA status were assessed in patients by enzyme-linked immunosorbent assay （EUSA） method. RESULTS： We found a significant increased frequency of HLA-DQBI＊0401 allele in Hpylori-positive patients with chronic gastritis when compared with healthy subjects [19 vs 0%, P = 1 × 10^-7, odds ratio （OR） = 4.96; 95% confidence interval （95% CI）, 3.87-6.35]. We also found a significant increased frequency of HLA-DQBI＊0501 in patients with diffuse-type gastric carcinoma in comparison with healthy individuals （P = 1 × 10^4, OR = 13.07; 95% CI, 2.82-85.14）.CONCLUSION： HLA-DQ locus may play a different role in the development of H pylori-related chronic gastritis and difffuse-type gastric adenocarcinoma in the Mexican Mestizo population.
基金The British Heart Foundation(Project Grant Award:PG PG/08/014)A postdoctoral research grant from the Fundación Ramón Areces(Spain)(to Dr.Montoro-Garcia S)
文摘AIM:To investigate lipid metabolism and the relationship with monocyte expression of the fatty acid translocase CD36 in South Asians.METHODS:An observational study of South Asians whom as an ethnic group have-a higher risk of developing diabetes.The susceptibility to diabetes is coupled with an earlier and more rapid progression of micro-,and macro-vascular complications.Twentynine healthy South Asian participants [mean age 34.6(8.9) years,76.2% male,mean body-mass index 25.0(5.2) kg/m2] were recruited from an urban residential area of central Birmingham(United Kingdom).The main outcomes measured were post prandial(30 min) and post absorptive(120 min) changes from fasting(0 min) in circulating lipoproteins,lipds and hormones,andmonocyte expression of CD36 post injection of a 75 g oral glucose challenge.The inducements of variations of monocyte CD36 expression were analysed.RESULTS:Our results showed evident changes in monocyte CD36 expression following the glucose challenge(P < 0.001).Non-esterified fatty acids(NEFA) levels decreased progressively during the challenge(P < 0.001),in contrast to increased cholesterol(but not triglyceride) concentrations within very low density lipoprotein(VLDL) and low density lipoprotein subfractions(P < 0.01).Levels of,glucose,serum triglycerides and high density lipoprotein cholesterol remained largely unchanged.Variations of monocyte CD36 were negatively(r =-0.47,P = 0.04) associated to fat from the diet and positively to carbohydrate from the diet(r = 0.65,P < 0.001).CONCLUSION:These data suggest that the initiation of VLDL genesis follows the consumption of glucose within this population,inferring that the sequestration of NEFA from these particles happens due to the increased availability of CD36 receptors.While these are preliminary results,it would appear that lifestyle exposures have a role in moderating the expression of CD36.
文摘Objective:To assess the role of polymerase chain reaction(PCR)in serum sauples,in the diagnosis of osteoarticular tuberculosis(OTB)in a setting where only clinical and imaging diagnoses determine the treatment.Methods:A total of 44 consecutive serum specimens were collected from clinically suspected OTB patients,based on clinical and radiological[X-ray or magnetic resonance imagng/computecl tomography]features.They were scrcened by in-house nested PCR.In addition,a few specimens were examined by Gram stain,acid-fast bacilli stain,histand routine bacterial culture.A total of 39 specimens were collected from patients suffering from other bone diseases of nontuberculous origin and included as negative controls.Results:of the 44 clinically suspected OTB patients,in-house nested PCR was positive in 40(91%)cases;PCR was negative in 38(97%)negative controls.Sensitivity and specificity of our in—house nested PCR was 90.3%and 97.4%,respectively.The PCR report was available within 48 h.It was possible to standardize serum PCR technique and in positive cases,a good n was observed in terms of an adequate treatment response.Conclusions:Nested PCR in serum samples is a rapid,highly sensitive and specific modality for OTB detection,PCR should be performed in addition to clinical evaluation,imaging studies,acidfast bacilli staining,culture and histopathology diagnosis,if possible.
文摘AIM: To establish a link between the risk of diabetes with haemoglobinopathies by examining available evidence of the effects of iron and blood glucose homeostasis from molecular to epidemiological perspectives.METHODS: A systematic literature search was performed using electronic literature databases using various search terms. The International Diabetes Federation World Atlas was used to generate a list of populations with high rates of diabetes. Pub Med, Scopus and Google Scholar were used to identify which of these populations also had a reported prevalence of haemoglobin abnormalities.RESULTS: Abnormalities in iron homeostasis leads to increases in reactive oxygen species in the blood. This promotes oxidative stress which contributes to peripheral resistance to insulin in two ways:(1) reduced insulin/insulin receptor interaction; and(2) β-cell dysfunction. Hepcidin is crucial in terms of maintaining appropriate amounts of iron in the body and is in turn affected by haemoglobinopathies. Hepcidin also has other metabolic effects in places such as the liver but so far the extent of these is not well understood. It does however directly control the levels of serum ferritin. High serum ferritin is found in obese patients and those with diabetes and a meta-analysis of the various studies shows that high serum ferritin does indeed increase diabetes risk.CONCLUSION: From an epidemiological standpoint, it is plausible that the well-documented protective effects of haemoglobinopathies with regard to malaria may have also offered other evolutionary advantages. By contributing to peripheral insulin resistance, haemoglobinopathies may have helped to sculpt the so-called "thrifty genotype", which hypothetically is advantageous in times of famine. The prevalence data however is not extensive enough to provide concrete associations between diabetes and haemoglobinopathies- more precise studies are required.
基金supported by grant from the CAMS Innovation Fund for Medical Sciences(CIFMS)2019-I2M-5-004(Q.C.)National Natural Science Foundation of China grants 81672674(R.L.),81872218(R.L.)and 81872208(L.J.)+3 种基金Science&Technology Department of Sichuan Province Applied Basic Research Program 2020YJ0451(T.R.)Fok Ying Tong Education Foundation grant 161036(R.L.)Young Talent Program of China National Nuclear Corporation CNNC201948(S.J.)Chengdu Medical College Fund Natural Science General Project CYZ18-17(S.J.).
文摘Oral squamous cell carcinoma(OSCC)become a heavy burden of public health,with approximately 300000 newly diagnosed cases and 145000 deaths worldwide per year.Nucleotide metabolism fuel DNA replication and RNA synthesis,which is indispensable for cell proliferation.But how tumor cells orchestrate nucleotide metabolic enzymes to support their rapid growth is largely unknown.Here we show that expression of pyrimidine metabolic enzyme dihydroorotate dehydrogenase(DHODH)is upregulated in OSCC tissues,compared to non-cancerous adjacent tissues.Enhanced expression of DHODH is correlated with a shortened patient survival time.Inhibition of DHODH by either shRNA or selective inhibitors impairs proliferation of OSCC cells and growth of tumor xenograft.Further,loss of functional DHODH imped de novo pyrimidine synthesis,and disrupt mitochondrial respiration probably through destabilizing the MICOS complex.Mechanistic study shows that transcriptional factor SOX2 plays an important role in the upregulation of DHODH in OSCC.Our findings add to the knowledge of how cancer cells co-opt nucleotide metabolism to support their rapid growth,and thereby highlight DHODH as a potential prognostic and therapeutic target for OSCC treatment.
基金supported by grants from the National Natural Science Foundation of China(Nos 82001047,81672674,81872218,81321002,81402245)Research Funding from West China School/Hospital of Stomatology Sichuan University(No.RCDWJS2020-8)the 111 Project of MOE China(Grant No.B14038).
文摘Oral squamous cell carcinoma(OSCC)is one of the most common cancers worldwide,and with 354864 new cases each year.Cancer metastasis,recurrence,and drug resistance are the main causes to cripples and deaths of OSCC patients.As potent growth factors,fibroblast growth factors(FGFs)are frequently susceptible to being hijacked by cancer cells.In this study,we show that FGF8 is upregulated in OSCC tissues and high FGF8 expression is related with a set of clinicopathologic parameters,including age,drinking,and survival time.FGF8 treatment enhances the invasive capability of OSCC cells.Lentivirus-based FGF8 expression promotes OSCC metastasis in a mouse lung metastasis model.Further,mechanistic study demonstrates that FGF8 induces epithelial–mesenchymal transition(EMT)in OSCC cells.These results highlight a pro-metastatic function of FGF8,and underscore the role of FGF8 in OSCC development.
