Association of cuproptosis-related signature with the prognosis of patients with head and neck squamous cell carcinoma.

Patients with head and neck squamous cell carcinoma (HNSCC) have a poor prognosis because of their high recurrence and metastasis rates. Cuproptosis is a novel type of copper-dependent cell death that differs from apoptosis, necroptosis, and cytosolic scorch death. We designed and validated an individualized cuproptosis-related gene (CRG) signature for risk evaluation and prognostic prediction in HNSCC patients. Ninety differentially expressed CRGs were found in HNSCC. Gene Ontology (GO) and Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway analyses were performed to investigate the functional involvement of CRGs in the Cancer Genome Atlas (TCGA) HNSCC cohort. A CRG signature was created using 10 genes after univariate and multivariate analysis. Kaplan Meier (KM) analysis showed that the survival rate of the high-risk group was significantly lower than that of the low-risk group. Multivariate regression analysis identified risk scores based on prognostic characteristics as independent prognostic indicators of HNSCC. Moreover, risk models are related to tumor mutational burden (TMB), tumor-infiltrating immune cells (TICs), immune checkpoints, clinical characteristics, and antitumor drug susceptibility. Furthermore, we found that CuCl2 treatment promoted cuproptosis in HNSCC cells, and that the expression levels of cuproptosis-related genes were altered by different doses of CuCl2. In summary, understanding the detailed molecular mechanisms of cuproptosis and its impact on overall survival (OS), and identifying potential therapeutic targets for HNSCC will provide potential insights for treatment.Communicated by Ramaswamy H. Sarma.

The Association between Oxidative Balance Score and Urinary Levels of 8-Hydroxydeoxyguanosine among Japanese Adults.

The oxidative balance score (OBS), wherein higher OBSs indicate lower oxidative stress, was designed to assess a composite measure of multiple pro-oxidant and antioxidant effects on an individual's oxidative stress status. This study aimed to evaluate whether OBSs were inversely associated with urinary levels of 8-hydroxydeoxyguanosine (8-OHdG)-an oxidative stress marker-among Japanese adults. This cross-sectional study was based on data obtained during 2010-2012. Overall, 7552 participants from the J-MICC Study Saga who answered a self-administered food frequency questionnaire were recruited for the final analysis. OBSs were calculated from 11 pro-oxidant and antioxidant lifestyle factors, including dietary intake, physical activity, and alcohol and smoking status. Urinary 8-OHdG values were corrected by creatinine level (ng/mg creatinine). Our findings revealed a higher total OBS was significantly associated with lower urinary 8-OHdG/creatinine levels after adjustment for covariates in men and women (p for trend < 0.01 in both sexes). We performed a multiple regression analysis of the association between OBSs and urinary 8-OHdG/creatinine levels stratified by age, body mass index (BMI), and menopausal status and found consistent negative associations in most groups for both sexes. No significant differences in the 60-64 age group for women (standardized ß = -0.09, p = 0.13) or BMI < 18.5 kg/m2 for men (standardized ß = -0.18, p = 0.17) were observed. A higher OBS had a strong inverse association with urinary 8-OHdG/creatinine levels in men and women among Japanese adults. The OBS might be a useful tool for evaluating the roles of oxidative stress-related lifestyle factors, including diet.

Exploring the underlying mechanisms of Ashitaba in the management of non-alcoholic fatty liver disease by integrating the analysis of transcriptomics and metabolomics.

Ashitaba seems to improve glucose intolerance and decrease triglyceride (TG) and total cholesterol (TC), which contribute to the development of non-alcoholic fatty liver disease (NAFLD). However, it remains to be explored the mechanism of Ashitaba in managing NAFLD. We determined the impact of Ashitaba on NAFLD, particularly its underlying mechanisms at the bioinformatic level. The established NAFLD mouse model was treated with or without Ashitaba, and the underlying mechanism was explored using transcriptomics paired with metabolomics. Ashitaba reduced obesity and liver steatosis in NAFLD mice. It identified 429 differentially expressed genes (DEGs) and verified 45 differential metabolites, especially those that alleviate NAFLD via the FXR signaling pathway. Our data may provide insight into the therapeutic impact of Ashitaba in the management of NAFLD and may be useful in clinical interventions for NAFLD.

Assessment of exposure and DNA damage from second-hand smoke using potential biomarker in urine: cigarettes and heated tobacco products.

Second-hand smoke exposure is an established cause of several adverse health effects. Tobacco smoke exposure in the environment has been improved by the WHO Framework Convention on Tobacco Control. However, concerns have been raised regarding the health effects of heated tobacco products. Analysis of tobacco smoke biomarkers is critical for assessing the health effects of second-hand tobacco smoke exposure. In this study, nicotine metabolites (nicotine, cotinine, trans-3'-hydroxycotinine) and carcinogenic 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol were analysed in the urine of non-smokers with or without passive exposure to cigarettes and heated tobacco products. In addition, 7-methylguanine and 8-hydroxy-2'-deoxyguanosine were simultaneously measured as DNA damage markers. The results revealed higher levels of urinary nicotine metabolites and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol in participants exposed to second-hand tobacco smoke (both cigarettes and heated tobacco products) at home. In addition, the urinary levels of 7-methylguanine and 8-hydroxy-2'-deoxyguanosine tended to be higher in the second-hand tobacco smoke-exposed group. The urinary levels of nicotine metabolites and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol were high in workplaces with no protection against passive smoking. These biomarkers will be useful for evaluating passive exposure to tobacco products.

PES1 is a biomarker of head and neck squamous cell carcinoma and is associated with the tumor microenvironment.

BACKGROUND: As a nucleolar protein associated with ribosome biogenesis in multiple cancer types, PES1 has been reported to be overexpressed, promoting cancer cell proliferation and invasion. However, in head and neck squamous cell carcinoma (HNSCC), the role of PES1 on the prognosis and immune infiltration remains unknown. METHODS: Multiple databases and qRT-PCR evaluated the expression of PES1 in HNSCC. The prognostic potential of PES1 in HNSCC patients was analyzed by Cox regression and Kaplan-Meier curves. Then, we used LASSO regression and stepwise multivariate Cox regression to construct the PES1-related risk assessment model. In addition, the association between PES1 and tumor immune microenvironment and drug sensitivity was explored by R packages. Finally, we used cell function assays to explore in HNSCC if PES1 influences tumor growth and metastasis. RESULTS: PES1 was significantly up-regulated in HNSCC and closely correlated with HPV status, tumor stage, clinical grade, and TP53 mutation status. Survival analysis suggested that PES1 is associated with worse survival outcomes, acting as an independent prognostic indicator for HNSCC. Our model also performed well in terms of prognosis prediction. Furthermore, tumor-infiltrating immune cells and antitumor drug susceptibility were negatively related to PES1 expression. Functionally, as for HNSCC cell lines in vitro, the knockdown of PES1 could inhibit proliferation, migration, and invasion. CONCLUSION: We have demonstrated that PES1 may be a promoter of tumor growth. PES1 holds excellent promise as a novel biomarker to assess the prognosis of patients with HNSCC and may guide immunotherapy.

Using the Unified Theory of Acceptance and Use of Technology (UTAUT) and e-health literacy(e-HL) to investigate the tobacco control intentions and behaviors of non-smoking college students in China: a cross-sectional investigation.

BACKGROUND: Non-smoking college students are starting to smoke in increasing numbers, which shows that their tobacco control situation seems not optimistic. The UTAUT and e-HL are commonly used models and theories to predict health behaviors, while there are few studies on tobacco control. This paper aims to study the influencing factors of tobacco control intention and behavior of non-smoking college students in China by combining the UTAUT and e-HL. METHODS: Based on the stratified sampling method, 625 college students from 12 universities were selected. Data were collected using a self-made questionnaire designed based on the UTAUT and e-health literacy scales. Data were analyzed by SPSS 22 and AMOS 26, including descriptive statistics, one-way variance analysis and structural equation model analysis. RESULTS: The results of one-way variance analysis showed that there were significant differences in the score of non-smoking college students' tobacco control intention or behavior by hometowns, monthly living expenses, and parents' smoking history. Performance expectancy, effort expectancy, social influence had direct positive effects on behavioral intention. Facilitating condition, behavioral intention had direct positive impacts on use behavior and e-HL had an indirect positive impact on use behavior. CONCLUSIONS: The combination of the UTAUT and e-HL can be used as an appropriate framework to predict the influencing factors of non-smoking college students' intention and behavior of tobacco control. Improving performance expectancy, effort expectancy, and e-HL among non-smoking college students, creating positive social environments, and providing facilitating condition are key aspects of increasing their tobacco control intention and behavior. It is also beneficial to promote the implementation of smoke-free campus and smoke-free family projects.

The highest region of muscle spindle abundance should be the optimal target of botulinum toxin A injection to block muscle spasms in rats.

Purpose: The effective relief of muscle spasticity requires prompt solutions in rehabilitation medicine. This study aimed to reveal that the highest region of muscle spindle abundance is the optimal target of botulinum toxin A (BTX-A) injections for relieve muscle spasm. Methods: Sixty adult, male Sprague-Dawley rats with lower limbs spasm caused by stroke after modeling, weighing (200 ± 20) g, were included in this study. The modelrats were divided into four groups: muscle spasm model group (group A), model rats treated with BTX-A injections into the middle of the muscle belly (group B), model rats treated with BTX-A injections into the center of the intramuscular nerve-dense region (INDR) (group C), and model rats treated with BTX-A injection into the center of the highest region of muscle spindle abundance (HRMSA) (group D). Groups B, C, and D were further divided into two subgroups: the 3rd and 6th days after BTX-A injection. The rats in each group were assigned modified Ashworth scale scores (MAS), and the changes in gastrocnemius muscle tone, wet muscle weight, and cross-sectional area of muscle fiber were detected. Results: Muscle spindle abundance was the highest in the upper part of the INDR. Group B experienced no significant changes in MAS, muscle tone, wet muscle weight, or cross-sectional area of the muscle fiber. Conversely, groups C and D experienced a decrease in these indicators. Group C experienced the most significant decrease in wet muscle weight and cross-sectional area of muscle fibers. Group D experienced the most notable decrease in MAS and muscle tone. There were no significant differences in the indicators between the 3rd and 6th days after BTX-A injections in group B and there were significant differences in the improvement in the indicators between the two subgroups in groups C and D, with group D experiencing more notable intersubgroup differences. Conclusion: The efficacy of BTX-A injections into the HRMSA is significantly superior to that of conventional BTX-A injections into the middle of the belly muscle or the INDR in the treatment of muscle spasms. Hence, HRMSA should be the optimal target of BTX-A to relieve muscle spasms.

MicroRNA in adenoid cystic carcinoma (Review).

Adenoid cystic carcinoma (ACC) usually arises in the salivary glands, and is a rare tumor, accounting for 1% of all head and neck cancer cases. According to estimates, there are 3­4.5 cases of ACC for every one million individuals. Numerous studies have reported the association between ACC and microRNAs (miRNAs/miRs). miRNAs are endogenous, non­coding small RNAs, 19­25 nt in length, that can regulate target gene expression at the post­transcriptional level. The aberrant expression of miRNAs may be associated with the prognosis and treatment of patients, as well as with tumorigenesis and tumor development. miRNAs are becoming reliable biomarkers for disease detection due to their varied characteristics, and miRNA target­based therapies are increasingly being used in clinical practice. The present review provides a brief introduction to ACC and the biogenesis of miRNAs. A summary of the miRNAs that have been validated by in vitro or in vivo studies is then presented, describing their role in ACC.

A hypoxia-related lncRNA model for prediction of head and neck squamous cell carcinoma prognosis.

BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) is one of the most common and highly heterogeneous malignancies worldwide. Increasing studies have proven that hypoxia and related long non-coding RNA (lncRNA) are involved in the occurrence and prognosis of HNSCC. The goal of this work is to construct a risk assessment model using hypoxia-related lncRNAs (hrlncRNAs) for HNSCC prognosis prediction and personalized treatment. METHODS: Transcriptome expression matrix, clinical follow-up data, and somatic mutation data of HNSCC patients were obtained from The Cancer Genome Atlas (TCGA). We used co-expression analysis to identify hrlncRNAs, then screened for differentially expressed lncRNAs (DEhrlncRNAs), and paired these DEhrlncRNAs. The risk model was established through univariate, least absolute shrinkage and selection operator (LASSO), and stepwise multivariate Cox regression. Finally, we assessed the model from multiple perspectives of tumor mutation burden (TMB), tumor immune infiltration, chemotherapeutic sensitivity, immune checkpoint inhibitor (ICI), and functional enrichment. RESULTS: The risk assessment model included 14 hrlncRNA pairs. The risk score was observed to be a reliable prognostic factor. The high-risk patients had an unfavorable prognosis and significant differences from the low-risk group in TMB and tumor immune infiltration. In the high-risk patients, the common immune checkpoints were down-regulated, including CTLA4 and PDCD1, and the sensibility to paclitaxel and docetaxel was higher. The functional enrichment analysis suggested that the low-risk group was accompanied by activated immune function. CONCLUSIONS: The risk assessment model of 14-hrlncRNA-pairs demonstrated a promising prognostic prediction for HNSCC patients and can guide personalized clinical treatment.

TYK2 correlates with immune infiltration: A prognostic marker for head and neck squamous cell carcinoma.

Tyrosine kinase 2 (TYK2) is a member of the Janus kinase (JAK) family and is involved in immune and inflammatory signaling. TYK2 is overexpressed in several types of cancers and promotes the invasion and proliferation of cancer cells. Nevertheless, the roles of TYK2 in the prognosis and immune infiltration of head and neck squamous cell carcinoma (HNSCC) remain to be elucidated. In this study, the expression of TYK2 in HNSCC was evaluated based on the data retrieved from multiple databases and quantitative real-time polymerase chain reaction (qRT-PCR) analysis. The prognostic potential of TYK2 in patients with HNSCC was analyzed by Kaplan-Meier curves and Cox regression analysis. A TYK2-related risk assessment model was subsequently constructed by Least Absolute Shrinkage and Selection Operator (LASSO) regression analysis and stepwise multivariate Cox regression analysis. The association between the expression of TYK2 and the tumor immune microenvironment, immune checkpoints, and drug sensitivity was explored various packages in R. Cell function assays were finally used for exploring the effects of TYK2 on the growth and metastasis of HNSCC tumors. The expression of TYK2 was significantly upregulated in HNSCC and was found to be closely correlated with HPV status, gender, clinical grade, and TP53 mutation status. Survival analysis suggested that TYK2 is associated with better survival outcomes and acts as an independent prognostic indicator of HNSCC. The model constructed herein also performed well in terms of predicting patient prognosis. The expression of TYK2 was positively associated with the population of tumor-infiltrating immune cells, expression of immune checkpoint genes, and antitumor drug susceptibility. Functionally, TYK2 knockdown significantly promoted the proliferation, migration, and invasion of HNSCC cell lines in vitro. The findings demonstrated that TYK2 could serve as a suppressor of tumor growth and holds significant promise as a novel biomarker for assessing the prognosis of patients with HNSCC and aid in immunotherapy against HNSCC.

Circular RNA-related CeRNA network and prognostic signature for patients with oral squamous cell carcinoma.

Background: Circular RNA (circRNA) has an important influence on oral squamous cell carcinoma (OSCC) progression as competing endogenous RNAs (ceRNAs). However, the link between ceRNAs and the OSCC immune microenvironment is unknown. The research aimed to find circRNAs implicated in OSCC carcinogenesis and progression and build a circRNA-based ceRNA network to create a reliable OSCC risk prediction model. Methods: The expression profiles of circRNA in OSCC tumors and normal tissues were assessed through RNA sequencing. From the TCGA database, clinicopathological data and expression patterns of microRNAs (miRNAs) and mRNAs were obtained. A network of circRNA-miRNA-mRNA ceRNA was prepared according to these differentially expressed RNAs and was analyzed through functional enrichment. Subsequently, based on the mRNA in the ceRNA network, the influence of the model on prognosis was then evaluated using a risk prediction model. Finally, considering survival, tumor-infiltrating immune cells (TICs), clinicopathological features, immunosuppressive molecules, and chemotherapy efficacy were analyzed. Results: Eleven differentially expressed circRNAs were found in cancer tissues relative to healthy tissues. We established a network of circRNA-miRNA-mRNA ceRNA, and the ceRNA network includes 123 mRNAs, six miRNAs, and four circRNAs. By the assessment of Genomes pathway and Kyoto Encyclopedia of Genes, it is found that in the cellular senescence, PI3K-AKT and mTOR signaling pathway mRNAs were mainly enrichment. An immune-related signature was created utilizing seven immune-related genes in the ceRNA network after univariate and multivariate analysis. The receiver operating characteristic of the nomogram exhibited satisfactory accuracy and predictive potential. According to a Kaplan-Meier analysis, the high-risk group's survival rate was signally lower than the group with low-risk. In addition, risk models were linked to clinicopathological characteristics, TICs, immune checkpoints, and antitumor drug susceptibility. Conclusion: The profiles of circRNAs expression of OSCC tissues differ significantly from normal tissues. Our study established a circRNA-associated ceRNA network associated with OSCC and identified essential prognostic genes. Furthermore, our proposed immune-based signature aims to help research OSCC etiology, prognostic marker screening, and immune response evaluation.

Construction of artificial neural network diagnostic model and analysis of immune infiltration for periodontitis.

Background: Periodontitis is a chronic inflammatory disease leading to tooth loss in severe cases, and early diagnosis is essential for periodontitis prevention. This study aimed to construct a diagnostic model for periodontitis using a random forest algorithm and an artificial neural network (ANN). Methods: Gene expression data of two large cohorts of patients with periodontitis, GSE10334 and GSE16134, were downloaded from the Gene Expression Omnibus database. We screened for differentially expressed genes in the GSE10334 cohort, identified key periodontitis biomarkers using a Random Forest algorithm, and constructed a classification artificial neural network model, using receiver operating characteristic curves to evaluate its diagnostic utility. Furthermore, patients with periodontitis were classified using a consensus clustering algorithm. The immune infiltration landscape was assessed using CIBERSOFT and single-sample Gene Set Enrichment Analysis. Results: A total of 153 differentially expressed genes were identified, of which 42 were downregulated. We utilized 13 key biomarkers to establish a periodontitis diagnostic model. The model had good predictive performance, with an area under the receiver operative characteristic curve (AUC) of 0.945. The independent cohort (GSE16134) was used to further validate the model's accuracy, showing an area under the receiver operative characteristic curve of 0.900. The proportion of plasma cells was highest in samples from patients with period ontitis, and 13 biomarkers were closely related to immunity. Two molecular subgroups were defined in periodontitis, with one cluster suggesting elevated levels of immune infiltration and immune function. Conclusion: We successfully identified key biomarkers of periodontitis using machine learning and developed a satisfactory diagnostic model. Our model may provide a valuable reference for the prevention and early detection of periodontitis.

Oxidative stress causes muscle structural alterations via p38 MAPK signaling in COPD mouse model.

INTRODUCTION: Sarcopenia is a complication of Chronic Obstructive Pulmonary Disease (COPD) that negatively affects physical activity and quality of life. However, the underlying mechanism by which COPD affects skeletal muscles remains to be elucidated. Therefore, we investigated the association between oxidative stress and structural alterations in muscles in elastase-induced emphysema mouse models. MATERIALS AND METHODS: Twelve-week-old male C57BL/6J mice were treated with either intratracheal porcine pancreatic elastase (PPE) dissolved in saline, or saline alone. The mice were euthanized 12 weeks after treatment, and the lungs and limb muscles were used for protein analysis of oxidative stress, p38 mitogen-activated protein kinase (p38 MAPK) signaling pathway and muscle atrophy signaling pathway related with oxidative stress. Furthermore, C57BL/6J mice treated with PPE or saline were analyzed for the effects of oral administration of astaxanthin or p38 inhibitor. RESULTS: The weight of the soleus muscle, proportion of type I muscle fibers, and cross-sectional areas of muscle fibers in the PPE group were lower than those in the control group. Oxidative stress marker levels in the PPE group were elevated in skeletal muscles. The p38 MAPK signaling pathway was activated in the soleus muscles, leading to the activation of the ubiquitin-proteasome system and autophagy. Astaxanthin and p38 inhibitors attenuated alterations in muscle structure through the deactivation of the p38 MAPK signaling pathway. CONCLUSIONS: This study provides first evidence in COPD mouse model that oxidative stress trigger a series of muscle structural changes. Our findings suggest a novel target for sarcopenia in COPD.

The Functional Mechanism of MicroRNA in Oral Lichen Planus.

Non-coding RNAs (ncRNAs) are transcribed from the genomes of mammals and other complex organisms, and many of them are alternately spliced and processed into smaller products. Types of ncRNAs include microRNAs (miRNAs), circular RNAs, and long ncRNAs. miRNAs are about 21 nucleotides long and form a broad class of post-transcriptional regulators of gene expression that affect numerous developmental and physiological processes in eukaryotes. They usually act as negative regulators of mRNA expression through complementary binding sequences in the 3'-UTR of the target mRNA, leading to translation inhibition and target degradation. In recent years, the importance of ncRNA in oral lichen planus (OLP), particularly miRNA, has attracted extensive attention. However, the biological functions of miRNAs and their mechanisms in OLP are still unclear. In this review, we discuss the role and function of miRNAs in OLP, and we also describe their potential functional roles as biomarkers for the diagnosis of OLP. MiRNAs are promising new therapeutic targets, but more work is needed to understand their biological functions.

Influence factors analysis of COVID-19 Prevention behavior of chinese Citizens: a path analysis based on the hypothetical model.

BACKGROUND: Under the outbreak of Coronavirus disease 2019 (COVID-19), a structural equation model was established to determine the causality of important factors that affect Chinese citizens' COVID-19 prevention behavior. METHODS: The survey in Qingdao covered several communities in 10 districts and used the method of cluster random sampling. The research instrument used in this study is a self-compiled Chinese version of the questionnaire. Of the 1215 questionnaires, 1188 were included in our analysis. We use the rank sum test, which is a non-parametric test, to test the influence of citizens'basic sociodemographic variables on prevention behavior, and the rank correlation test to analyze the influencing factors of prevention behavior. IBM AMOS 24.0 was used for path analysis, including estimating regression coefficients and evaluating the statistical fits of the structural model, to further explore the causal relationships between variables. RESULTS: The result showed that the score in the prevention behavior of all citizens is a median of 5 and a quartile spacing of 0.31. The final structural equation model showed that the external support for fighting the epidemic, the demand level of health information, the cognition of (COVID-19) and the negative emotions after the outbreak had direct effects on the COVID-19 prevention behavior, and that negative emotions and information needs served as mediating variables. CONCLUSIONS: The study provided a basis for relevant departments to further adopt epidemic prevention and control strategies.

Urinary biomarkers for secondhand smoke and heated tobacco products exposure.

Concerns have recently grown about the health effects of secondhand smoke exposure and heated tobacco products. The analysis of tobacco smoke biomarkers is critical to assess the health effects of tobacco smoke exposure. For this purpose, the simultaneous determinations of exposure markers and health effect markers would provide a better evaluation of smoke exposure. In this study, nicotine metabolites (nicotine, cotinine, trans-3'-hydroxycotinine) and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol in urine were analyzed as exposure markers. The DNA damage markers, 7-methylguanine and 8-hydroxy-2'-deoxyguanosine, were simultaneously measured as health effect markers. The results revealed significant levels of urinary nicotine metabolites and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol in the subjects exposed to secondhand smoke and heated tobacco products. In addition, the urinary levels of 7-methylguanine and 8-hydroxy-2'-deoxyguanosine tended to be high for secondhand smoke and heated tobacco products exposures, as compared to those of non-smokers. These biomarkers will be useful for evaluating tobacco smoke exposure.

Tailored Synthesis of Skeletally Diverse Stemona Alkaloids through Chemoselective Dyotropic Rearrangements of ß-Lactones.

The collective synthesis of skeletally diverse Stemona alkaloids featuring tailored dyotropic rearrangements of ß-lactones as key elements is described. Specifically, three typical 5/7/5 tricyclic skeletons associated with stemoamide, tuberostemospiroline and parvistemonine were first accessed through chemoselective dyotropic rearrangements of ß-lactones involving alkyl, hydrogen, and aryl migration, respectively. By the rational manipulation of substrate structures and reaction conditions, these dyotropic rearrangements proceeded with excellent efficiency, good chemoselectivity and high stereospecificity. Furthermore, several polycyclic Stemona alkaloids, including saxorumamide, isosaxorumamide, stemonine and bisdehydroneostemoninine, were obtained from the aforementioned tricyclic skeletons through late-stage derivatizations. A novel visible-light photoredox-catalyzed formal [3+2] cycloaddition was also developed, which offers a valuable tool for accessing oxaspirobutenolide and related scaffolds.

Health examination results and work environment factors affecting urinary 8-hydroxy-2'-deoxyguanosine levels.

OBJECTIVE: Oxidative stress is considered to cause lifestyle-related diseases, including cancer. Urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) is widely analyzed as an oxidative stress marker. We extensively scrutinized the relationships between 8-OHdG levels and lifestyle choices as carcinogenic factors. METHODS: In this study, we investigated health examination results and working conditions affecting urinary 8-OHdG levels in 503 male workers. RESULTS: The urinary 8-OHdG level was positively associated with high blood sugar and leanness in smokers. In addition, urinary 8-OHdG tended to increase with organic solvent or hydrochloric acid exposure, as well as long working hours. On the other hand, the urinary 8-OHdG level was negatively associated with high plasma LDL-cholesterol levels in non-smokers and anemia. CONCLUSION: According to the results, anemia decreased the oxidative stress, regardless of smoking status, while leanness or high blood sugar increased the oxidative stress in smokers, and the presence of plasma cholesterol contributed to the lower oxidative stress in non-smokers. Certain types of occupational exposure may cause oxidative stress. The measurement of urinary 8-OHdG at annual health checks may be a useful biomarker for preventing lifestyle- and work-related diseases.

Diurnal and day-to-day variation of urinary oxidative stress marker 8-hydroxy-2'-deoxyguanosine.

The urinary 8-hydroxy-2'-deoxyguanosine levels have been widely used as a biomarker of oxidative stress. The purpose of this study is to investigate the diurnal and day-to-day variations of urinary 8-hydroxy-2'-deoxyguanosine levels. For the diurnal variation, the urine samples were collected at the time of awakening and every 2 h, from 10:00 to 22:00, from 6 healthy participants. For the day-to-day variation, the urine samples were collected at the time of awakening for 35 consecutive days, from 27 healthy participants. As a result, no differences were observed in the diurnal urinary 8-hydroxy-2'-deoxyguanosine levels, and each subject had a characteristic 8-hydroxy-2'-deoxyguanosine level. On the other hand, the daily 8-hydroxy-2'-deoxyguanosine values showed a certain range of variation reflecting lifestyle factors, such as stress status, exercise, sleep time, drinking and diet. In conclusion, urinary 8-hydroxy-2'-deoxyguanosine may be a useful biomarker to control and prevent oxidative stress-related diseases, if the certain range of day-to-day variations of urinary 8-hydroxy-2'-deoxyguanosine is known. Even with only one measurement per year, the baseline urinary 8-hydroxy-2'-deoxyguanosine level could be achieved in a few years by incorporating the 8-hydroxy-2'-deoxyguanosine measurement as part of an annual health check. As the number of subjects was limited, further studies are needed for practical applications.

Effects of smoking cessation on biological monitoring markers in urine.

INTRODUCTION: Urinary nicotine and cotinine levels are often measured as biomarkers for tobacco smoke exposure. However, these biomarkers are not appropriate to evaluate the effects of quitting smoking for several days, because of their short half-lives. In this study, we focused on the changes in the urinary 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) levels of 55 patients in a smoking cessation program, because of the long half-life. At the same time, urinary 7-methylguanine (m7Gua) and 8-hydroxy-2'-deoxyguanosine (8-OHdG), as DNA damage markers of cigarette smoking, were also measured. RESULTS: In the subjects who completed the quit-smoking program (18 subjects out of 55), the urinary nicotine and cotinine levels decreased to 1.7 and 0.2% at 8 weeks after the first visit to the clinic. By contrast, the NNAL levels decreased to 12.3% at 8 weeks after quitting smoking. During the same period, the urinary m7Gua levels significantly decreased, from 27.32 µg/mg creatinine to 14.17 µg/mg creatinine by the elimination of subjects who showed increased levels of NNAL during the smoking cessation program. The 8-OHdG levels were also reduced within the same period, but were not significantly different. From the all data analysis, the urinary levels of cotinine and NNAL positively correlated with the level of m7Gua. CONCLUSIONS: NNAL may be an appropriate exposure marker for evaluating the smoking status of patients in a smoking cessation program. The urinary cotinine and NNAL levels positively correlated with the m7Gua levels.