Short-term impact of exposure to ambient air volatile organic compounds on daily clinic visits for urticaria in Kaohsiung, Taiwan.

BACKGROUND: Air volatile organic compounds (VOCs) cause allergic reaction mainly via the respiratory tract or skin. OBJECTIVE: This study aimed to investigate the association between daily visits by patients with urticaria and short-term changes in exposure to ambient air VOCs. METHODS: The dependent variable was information from patients with urticaria at a medical center in Kaohsiung, Taiwan, from 2014/01/01 to 2018/07/31. The multivariable model included one-day average 75th percentile values of air VOCs and meteorologic data retrieved from Taiwan Air Quality Monitoring Network database, and was analyzed using a case-crossover study design and conditional logistic regression. RESULTS: Total daily clinic visits for urticaria were significantly positively associated with higher levels of 4 VOCs (ethylbenzene, toluene, m-/p-xylene, and o-xylene (adjusted odds ratio (AOR: 1.03-1.28)) on the visit days, and 10 VOC levels on the fourth lag day (benzene, ethylbenzene, toluene, m-/p-xylene, o-xylene, 1,3,5-trimethylbenzene, n-hexane, methylcyclohexane, cyclohexane, and ethylene (AOR: 1.02-3.02)). Analyses of age and gender subgroups revealed that men showed resistance on the visit day, and women, older, and younger patients were more vulnerable. Men were influenced by higher benzene levels (AOR = 1.24) on the fourth lag day. Higher values of more than 6 VOCs on the fourth lag day significantly affected women, younger and older patients (AOR: 1.04-6.5). The most notable VOCs were methylcyclohexane (women AOR = 3.28, younger AOR = 3.82) and 1,3,5-trimethylbenzene (women AOR = 2.77, older AOR = 6.5) on the fourth lag day, which had the lowest concentrations but highest influence. CONCLUSION: The concentration of certain air VOCs significantly affected daily visits for urticaria.

Vesicular Lymphomatoid Papulosis With DUSP22-IRF4 Rearrangement on Chromosome 6p25.3: A Case Report.

ABSTRACT: Lymphomatoid papulosis (LyP) with DUSP22-IRF4 rearrangement on chromosome 6p25.3 is a newly identified subtype of LyP. It is characterized by an older age of onset, localized skin lesions, with good prognosis, and it resembles a hybrid of LyP types B and C in histopathology. A limited number of cases have been reported so far. In this article, we reported a case of a 72-year-old man with recurrent episodes of widespread multiple discrete papular or vesicular eruptions on a region of the head, trunk, and 4 extremities for about 3 years. Histopathological examination of a vesicle revealed a subepidermal blister with abundant atypical lymphocytes in the vesicular space, band-like infiltrates in the papillary dermis, along with epidermotropism and pilosebaceous structure involvement. Fluorescence in situ hybridization analysis further demonstrated DUSP22-IRF4 rearrangement on chromosome 6p25.3. A diagnosis of vesicular LyP with this rare subtype was made according to the clinical and pathological findings.

Adult-onset inflammatory linear verrucous epidermal nevus: Immunohistochemical studies and review of the literature.

Adult-onset inflammatory linear verrucous epidermal nevus (ILVEN) is an uncommon cutaneous disease compared to childhood-onset ILVEN. The typical histopathologic features are alternating parakeratosis and orthokeratosis with an absent granular layer underneath parakeratosis, in contrast to a thickened granular layer below the foci of orthokeratosis in psoriasiform epidermal hyperplasia. Herein, we present a 49-year-old woman with typical clinical and histopathologic characteristics of adult-onset ILVEN, including linear arrangement of thick scaly papules and plaques localized on the medial side of her right leg, ankle, and foot. Immunohistochemical studies included involucrin, Ki-67, and keratin-10. Compared to the staining pattern in psoriasis, the expression of involucrin in this case was of lower intensity and localized to upper epidermal layers with relatively less extensive staining beneath regions of parakeratosis as compared to orthokeratosis; Ki-67 showed lower basal layer proliferative activity; and keratin-10 showed a greater intensity of staining within suprabasal epidermis.

The influence of immunosuppressants on the non-melanoma skin cancer among patients with systemic lupus erythematosus and primary Sjögren's syndrome: a nationwide retrospective case-control study in Taiwan.

OBJECTIVES: To investigate the influence of corticosteroids and hydroxychloroquine on the association with non-melanoma skin cancer (NMSC) among patients with systemic lupus erythematosus (SLE) or primary Sjögren's syndrome (pSS). METHODS: This nationwide retrospective case-control study retrieved data from Taiwan National Health Insurance Research Database from 1995-2013. Cases with newly-diagnosed NMSC (n=19,603) and controls without NMSC were matched in a 1:1 ratio according to age, sex, and reference date. SLE, pSS, NMSC, and co-morbidities were determined by ICD-9-CM code. Cumulative drug exposures were defined by cumulative dosages or total defined daily dose (TDDD) of the Anatomical Therapeutic Chemical code of medicines. The analysis used conditional logistic regression and adjusted for age, sex, residential area, occupation, and co-morbidities. Case-control studies cannot infer the causality. RESULTS: Compared to patients without SLE or pSS, the patients with SLE had significantly higher associations with NMSC (cases/controls: n=23/10, adjusted odds ratio (AOR)=2.33, 95% confidence interval (CI) 1.08-5.01), particularly those using corticosteroids with a cumulative dosage >5g (cases/controls: n=17/5, AOR=2.96, 95%CI 1.06-8.23); and those using hydroxychloroquine with a cumulative dosage >100 TDDD (cases/controls: n=18/6, AOR=2.7, 95%CI 1.04-6.98). The patients with pSS had significantly higher associations with NMSC (cases/controls: n=28/11, AOR=2.56, 95%CI 1.25-5.23), particularly those using hydroxychloroquine with a cumulative dosage >100TDDD (cases/controls: n=20/4, AOR=5.41, 95%CI 1.82-16.11), and those using corticosteroids with a cumulative dosage >1g (cases/controls: n=13/3, AOR=4.92, 95%CI 1.37-17.61). CONCLUSIONS: The patients with SLE or pSS had significantly increased associations with NMSC, especially those receiving higher cumulative doses of corticosteroids and hydroxychloroquine.

The influence of disease-modifying anti-rheumatic drugs and corticosteroids on the association between rheumatoid arthritis and skin cancer: a nationwide retrospective case-control study in Taiwan.

OBJECTIVES: To investigate the influence of corticosteroids and disease-modifying anti-rheumatic drugs (DMARDs, including conventional synthetic and biologic DMARDs) treatment on the association between rheumatoid arthritis (RA) and non-melanoma skin cancer (NMSC). METHODS: This nationwide retrospective case-control study retrieved data from Taiwan National Health Insurance Research Database during 1995-2013. Cases with newly-diagnosed NMSC (n=19,603) were matched with control without NMSC in a 1:1 ratio according to age, sex, and reference date. The aforementioned association was analysed using conditional logistic regression and adjustments for age, sex, residential regions, occupations, and co-morbidities. Causality cannot be inferred by case-control study. RESULTS: Compared to patients without RA, the patients with RA had a significantly higher association with NMSC (adjusted odds ratio (AOR)=2.23, 95% confidence interval (CI) 1.6-3.1, p<0.001), especially those using cyclosporine (AOR=5.7, 95%CI 2.2-14.86; ≥65 years: AOR=7.28, 95%CI 2.16-24.56), etanercept (AOR=5.27, 95%CI 1.15-24.27; ≥65 years: AOR=8.95, 95%CI 1.12-71.85), and d-penicillamine (AOR=4.79, 95%CI 1.63-14.12; ≥65 years: AOR=3.81, 95%CI 1.26-11.52); those using higher cumulative doses of corticosteroids and methotrexate (corticosteroids: >10g: AOR=2.96, 95%CI 1.67-5.22; >10g and ≥65years: AOR=3.5, 95%CI 1.77-6.92; methotrexate: 1-3g: AOR=2.57, 95%CI 1.13-5.82; >3g: AOR=4.64, 95%CI 1.74-12.4; >3g and ≥65 years: AOR=10.17, 95%CI 2.34-44.26); and those using more kinds of DMARDs (any 3: AOR=3.72, 95%CI 1.67-8.26; any 5: AOR=2.81, 95%CI 1.13-7.04; any 6: AOR=5.23, 95%CI 1.14-24.14; 7-8: AOR=4.06, 95%CI 1.14-14.49). CONCLUSIONS: The patients with RA had significantly increased associations with NMSC, especially those receiving cyclosporine, etanercept, and d-penicillamine; higher cumulative doses of corticosteroids and methotrexate; or more kinds of DMARDs in combination or in sequence. The aforementioned associations were much stronger in the elderly.

The mechanism of protriptyline-induced Ca2+ movement and non-Ca2+-triggered cell death in PC3 human prostate cancer cells.

Protriptyline, a tricyclic anti-depressant, is used primarily to treat the combination of symptoms of anxiety and depression. However, the effect of protriptyline on prostate caner is unknown. This study examined whether the anti-depressant protriptyline altered Ca(2+) movement and cell viability in PC3 human prostate cancer cells. The Ca(2+)-sensitive fluorescent dye fura-2 was used to measure [Ca(2+)](i). Protriptyline evoked [Ca(2+)](i) rises concentration-dependently. The response was reduced by removing extracellular Ca(2+). Protriptyline-evoked Ca(2+) entry was inhibited by store-operated channel inhibitors (nifedipine, econazole and SKF96365), protein kinase C activator (phorbol 12-myristate 13 acetate, PMA) and protein kinase C inhibitor (GF109203X). Treatment with the endoplasmic reticulum Ca(2+) pump inhibitor 2,5-di-tert-butylhydr-oquinone (BHQ) in Ca(2+)-free medium inhibited 60% of protriptyline-evoked [Ca(2+)](i) rises. Conversely, treatment with protriptyline abolished BHQ-evoked [Ca(2+)](i) rises. Inhibition of phospholipase C with U73122 suppressed 50% of protriptyline-evoked [Ca(2+)](i) rises. At concentrations of 50-70 µM, protriptyline decreased cell viability in a concentration-dependent manner; which were not reversed by chelating cytosolic Ca(2+) with 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid-acetoxymethyl ester (BAPTA/AM). Collectively, in PC3 cells, protriptyline evoked [Ca(2+)](i) rises by inducing phospholipase C-associated Ca(2+) release from the endoplasmic reticulum and other stores, and Ca(2+) influx via protein kinase C-sensitive store-operated Ca(2+) channels. Protriptyline caused cell death that was independent of [Ca(2+)](i) rises.

A survey of dermatological diseases among older male adults of a Veterans Home in Southern Taiwan.

BACKGROUNDS: The dermatologic diseases of the dependent elderly require special attention. METHODS: This screening and treatment service of dermatological diseases was conducted in a Veterans Home in Southern Taiwan. RESULTS: A total of 337 male residents were screened with mean age 83 years (range 46-99). 271 (80.4 %) residents were in dependent status. Their skin diseases were recorded and the distribution pattern was compared with those in the other studies. Comparing by Chi-square test, scabies, bacterial infection, chronic ulcers, pruritus, and brown spots on the legs were present significantly in certain major systemic diseases, respectively. Higher prevalence of certain skin diseases was related to the severity of disability or major systemic diseases of the residents. Actinic keratosis and non-melanoma skin cancers were early detected and managed. CONCLUSIONS: The distribution patterns of skin diseases in a Veterans Home were unique. It provides the evidences on appropriate management and key nursing points for dependent elderly.

Effect of NPC-14686 (Fmoc-l-Homophenylalanine) on Ca²âº Homeostasis and Viability in OC2 Human Oral Cancer Cells.

The effect of the anti-inflammatory compound NPC-14686 on intracellular Ca²âº concentration ([Ca²âº](i)) and viability in OC2 human oral cancer cells was investigated. The Ca²âº-sensitive fluorescent probe fura-2 was used to examine [Ca²âº](i). NPC-14686 induced [Ca²âº](i) rises in a concentration-dependent fashion. The effect was reduced approximately by 10% by removing extracellular Ca²âº. NPC-14686- elicited Ca²âº signal was decreased by nifedipine, econazole, SKF96365, and GF109203X. In Ca²âº-free medium, incubation with the endoplasmic reticulum Ca²âº pump inhibitor thapsigargin or 2,5-di-tert-butylhydroquinone (BHQ) abolished NPC-14686-induced [Ca²âº](i) rises. Conversely, pretreatment with NPC-14686 abolished thapsigargin or BHQ-induced [Ca²âº](i) rises. Inhibition of phospholipase C with U73122 abolished NPC-14686-induced [Ca²âº](i) rises. At 20-100 µM, NPC-14686 inhibited cell viability, which was not reversed by chelating cytosolic Ca²âº with 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'- tetraacetic acid-acetoxymethyl ester (BAPTA/AM). NPC-14686 between 20 µM and 40 µM also induced apoptosis. Collectively, in OC2 cells, NPC-14686 induced [Ca²âº](i) rises by evoking phospholipase C-dependent Ca²âº release from the endoplasmic reticulum and Ca²âº entry via protein kinase C-regulated store-operated Ca²âº channels. NPC-14686 also caused Ca²âº-independent apoptosis.

Effect of methoxychlor on Ca²âº homeostasis and apoptosis in HA59T human hepatoma cells.

Methoxychlor, an organochlorine pesticide, is thought to be an endocrine disrupter that affects Ca²âº homeostasis and cell viability in different cell models. This study explored the action of methoxychlor on cytosolic free Ca²âº concentrations ([Ca²âº]i) and apoptosis in HA59T human hepatoma cells. Fura-2, a Ca²âº-sensitive fluorescent dye, was applied to measure [Ca²âº]i. Methoxychlor at concentrations of 0.1-1 µM caused a [Ca²âº]i rise in a concentration-dependent manner. Removal of external Ca²âº abolished methoxychlor's effect. Methoxychlor-induced Ca²âº influx was confirmed by Mn²âº-induced quench of fura-2 fluorescence. Methoxychlor-induced Ca²âº entry was inhibited by nifedipine, econazole, SK&F96365, and protein kinase C modulators. Methoxychlor killed cells at concentrations of 10-130 µM in a concentration-dependent fashion. Chelation of cytosolic Ca²âº with 1,2-bis(2-aminophenoxy) ethane-N,N,N',N'-tetraacetic acid/AM (BAPTA/AM) did not prevent methoxychlor's cytotoxicity. Methoxychlor (10 and 50 µM) induced apoptosis concentration-dependently as determined by using Annexin V/propidium iodide staining. Together, in HA59T cells, methoxychlor induced a [Ca²âº]i rise by inducing Ca²âº entry via protein kinase C-sensitive Ca²âº-permeable channels, without causing Ca²âº release from stores. Methoxychlor also induced apoptosis that was independent of [Ca²âº]i rises.

Effect of deoxycholic acid on Ca2+ movement, cell viability and apoptosis in human gastric cancer cells.

Deoxycholic acid (DOA) is one of the secondary bile acids used as a mild detergent for the isolation of membrane associated proteins. This study examined whether the secondary bile acid, DOA, altered Ca(2+) movement, cell viability and apoptosis in SCM1 human gastric cancer cells. The Ca(2+)-sensitive fluorescent dye fura-2 was used to measure [Ca(2+)]i. DOA-evoked [Ca(2+)]i rises concentration dependently. The response was reduced by removing extracellular Ca(2+). DOA-evoked Ca(2+) entry was inhibited by store-operated Ca(2+) channel inhibitors (nifedipine, econazole and SKF96365), the protein kinase C (PKC) activator phorbol 12-myristate 13 acetate (PMA) and the PKC inhibitor GF109203X. In Ca(2+)-free medium, treatment with the endoplasmic reticulum Ca(2+) pump inhibitor thapsigargin (TG) abolished DOA-evoked [Ca(2+)]i rises. Conversely, treatment with DOA abolished TG-evoked [Ca(2+)]i rises. Inhibition of phospholipase C with U73122 abolished DOA-evoked [Ca(2+)]i rises. At 100-500 µM, DOA decreased cell viability, which was not changed by chelating cytosolic Ca(2+) with 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid-acetoxymethyl ester (BAPTA/AM). DOA between 100 and 300 µM also induced apoptosis. Collectively, in SCM1 cells, DOA-induced [Ca(2+)]i rises by evoking phospholipase C-dependent Ca(2+) release from the endoplasmic reticulum and Ca(2+) entry via store-operated Ca(2+) channels. DOA also caused Ca(2+)-independent apoptosis.

Confluent and reticulate papillomatosis treated with minocycline and tazarotene.

Confluent and reticulate papillomatosis (CRP) (also known as Gougerot-Carteaud syndrome) is a rare disorder that usually presents sporadically, with onset typically occurring in young .adulthood. We present 2 cases of CRP with typical clinical manifestations of scaly, dull, brownish, confluent and reticulate macules and patches. On examination using a potassium hydroxide (KOH) preparation and Periodic acid-Schiff (PAS) stain, both patients' lesions were negative for fungal elements; in patient 2, bacteria colonies accumulated in follicular orifices without perifollicular inflammation in the dermis. Both patients responded well to treatment with oral minocycline and topical tazarotene and showed clearance of CRP lesions at 12- and 8-month follow-up, respectively.

Effects of Mindfulness-Based Cognitive Therapy on Major Depressive Disorder with Multiple Episodes: A Systematic Review and Meta-Analysis.

This study synthesizes the effect of mindfulness-based cognitive therapy (MBCT) on depression and suicidal ideation among patients with major depressive disorder (MDD). During treatment, patients with MDD may experience repeated episodes, negative counseling, and suicidal ideation, which can lead to further depression and ultimately affect quality of life. Recent studies have shown that MBCT can improve the level of depression and suicidal ideation in patients with MDD. A systematic review and meta-analysis of randomized controlled trials was conducted. The literature search for articles up to December 2021 was performed in the following electronic databases: Airiti Library, PsycINFO, CINAHL, Cochrane Library, PubMed/MEDLINE, ProQuest, and the Index of the Taiwan Periodical Literature System. Records were independently evaluated by two reviewers. Disagreements were resolved through consensus. The quality of study was evaluated using the Modified Jadad Scale score. A meta-analysis was performed using Review Manager Version 5.3.5 software with a random-effects model. Thirteen studies (1159 participants) investigating MBCT for patients with MDD were included. The MBCT sessions lasted 1.5-2.5 h and were delivered by therapists five times per week for 8 weeks. The meta-effects of MBCT among patients with MDD showed significant improvement in depression and suicidal ideation. Future research should evaluate the long-term effects of MBCT. MBCT is relatively convenient and effective for preventing and alleviating depression and suicidal ideation. Further research can provide detailed suggestions for effective MBCT implementation.

Poor Mental Health in Caregivers of Children with Attention-Deficit/Hyperactivity Disorder and Its Relationships with Caregivers' Difficulties in Managing the Children's Behaviors and Worsened Psychological Symptoms during the COVID-19 Pandemic.

The coronavirus disease 2019 (COVID-19) pandemic has thrown out a challenge to caregivers of children with attention-deficit/hyperactivity disorder (ADHD). The present study examined the factors related to the poor general mental health state of the caregivers of children with ADHD during the COVID-19 pandemic, including (1) difficulties of caregivers in asking their child to adopt protective behaviors against COVID-19, (2) difficulties of caregivers in managing the child's daily performance, and (3) worsened psychological symptoms in children. In total, 161 caregivers completed an online questionnaire to provide data regarding their general mental health state and difficulties in asking their child with ADHD to adopt protective behaviors against COVID-19 and in managing the child's after-school learning, sleep routine, and internet use, as well as worsened psychological symptoms. The results of multivariate logistic regression analysis demonstrated that caregivers' difficulties in managing ADHD children's self-protective behaviors and after-school learning and the children's worsened emotional symptoms were significantly associated with poor caregiver general mental health state. An intervention that enhances the mental health of caregivers of children with ADHD during the COVID-19 pandemic by addressing their difficulties in managing the children's behaviors and psychological problems is warranted.

Metformin Treatment Suppresses Melanoma Cell Growth and Motility Through Modulation of microRNA Expression.

Melanoma is a highly aggressive cancer with high mortality in advanced stages.Metformin is an oral biguanide drug used for diabetes and has demonstrated positive effects oncancer prevention and treatment. Herein, we found that metformin significantly suppressedmelanoma cancer cell motility and growth through inducing cell cycle arrest at the G2/M phase andpromoting cell apoptosis. Using the next-generation sequencing approach, we identified threeupregulated microRNAs (miRNA; miR-192-5p, miR-584-3p, and miR-1246) in melanoma cellstreated with metformin. Among these, we examined the roles of miR-192-5p and miR-584-3p anddiscovered that they significantly suppressed melanoma cell motility. Furthermore, they inhibitedmelanoma cell growth through destroying cell cycle progression and inducing cell apoptosis. Usingmicroarray and bioinformatics approaches for identifying putative target genes, Epidermal growthfactor (EGF) containing fibulin-like extracellular matrix protein 1 (EFEMP1) gene for miR-192-5pand an isoform of the secretory carrier membrane proteins (SCAMP3) gene for miR-584-3p could besilenced through targeting their 3'UTR region directly. EFEMP1 and SCAMP3 knockdownsignificantly suppressed melanoma cell growth, but only EFEMP1 knockdown inhibited its motilityabilities. Our findings indicated that miR-192-5p and miR-584-3p might contribute to metformininducedgrowth and motility suppression in melanoma cells through silencing their target genesEFEMP1 and SCAMP3.

The association between immunoexpression levels of oxidant and antioxidant enzymes and lip squamous cell carcinoma.

The aim of this study was to investigate the associations among the immunoexpression levels of manganese superoxide dismutase (Mn-SOD), glutathione peroxidase (GPx), and myeloperoxidase (MPO) in lip squamous cell carcinoma (LSCC) tissues and the clinicopathological characteristics, and prognostic factors in patients with LSCC. The immunoexpression levels of Mn-SOD, GPx, and MPO were examined in 76 LSCC tissue samples using immunohistochemical staining on tissue microarray slides, and compared to those in normal lip mucosa adjacent to venous lakes (normal controls), normal tissue adjacent to corresponding tumors (NTACT), and recurrent tumors. Associations between immunoexpression levels and clinicopathological characteristics were analyzed using the Student's t-test. The prognostic factors were analyzed using Cox regression. The immunoexpression levels of Mn-SOD, GPx, and MPO were significantly different among the normal controls, NTACTs, tumors, and recurrent tumors (Mn-SOD: p = 0.001, GPx: p < 0.001, MPO: p < 0.001). Lower lip cancer was associated with higher Mn-SOD immunoexpression levels (p = 0.04) and probably indicated higher oxidative stress. Lymph node involvement with a lower immunoexpression level of MPO (p = 0.007) indicated compensatory mechanism to attenuate oxidative damage. A low Mn-SOD immunoexpression level was borderline significantly associated with a worse prognosis for disease-specific survival, and it was probably related to a lower capacity for coping with oxidative stress.

Clinicopathological study of lip cancer: a retrospective hospital-based study in Taiwan.

To evaluate the clinicopathological characteristics, high-risk lifestyle factors (HRLF: chronic exposure to sun, betel quid, alcohol, and tobacco), and prognostic factors of lip cancer. The hospital records of patients with pathologically confirmed lip squamous cell carcinoma (LSCC, n = 112) and lip basal cell carcinoma (LBCC, n = 21) were reviewed. Differences in clinicopathological characteristics between LSCC and LBCC, upper and lower lip, and status of second primary tumors were compared by chi-square test and logistic regression. The prognostic factors for LSCC were analyzed by Cox regression. Compared with LBCC patients, LSCC patients were men-predominant (p < 0.001), had younger ages at onset (p < 0.001), and higher rates of lower lips involvement (p < 0.001) and HRLFs. Patients with second primary tumors were highly associated with lower lip cancer involvement (adjusted odds ratio = 2.91, p = 0.03). Patients with lower lip cancer had more HRLFs with an increasing linear trend (p = 0.004). The poorer prognostic factors of LSCC for disease-specific survival were advanced stage III/IV [crude hazard ratio (CHR) = 11.16, p < 0.001], tumor dimension >4 cm (CHR = 8.19, p = 0.006), lymph node involvement (CHR = 11.48, p < 0.001), and recurrence (CHR = 3.96, p = 0.01); whereas for disease-free survival were moderately to poorly differentiated LSCC (CHR = 4.97, p = 0.002) and alcohol consumption (CHR = 3.13, p = 0.04). LSCC and lower lip cancer were highly associated with HRLFs.

Risk of skin cancer in patients with diabetes mellitus: A nationwide retrospective cohort study in Taiwan.

Increasing evidence suggests that certain types of cancers are more common in people with diabetes mellitus (DM). This study aimed to investigate the risk of skin cancer in patients with DM in Taiwan. In this retrospective cohort study using data from the Taiwan Longitudinal Health Insurance Research Database, the risk of developing overall skin cancer, including nonmelanoma skin cancer (NMSC) and melanoma, was compared by Poisson regression analysis and Cox regression analysis between the DM and non-DM cohorts. The DM cohort with newly diagnosed DM (n = 41,898) and a non-DM cohort were one-to-one matched by age, sex, index date, and comorbidities (coronary artery disease, hyperlipidemia, hypertension, chronic kidney disease, chronic obstructive pulmonary disease, and obesity). Compared with non-DM cohort statistically, for the people with DM aged ≥60 years, the incidence rates of overall skin cancer and NMSC were significantly higher (overall: DM/non-DM: number [n] = 99/76, incidence rate ratio [IRR] = 1.44, P = 0.02; NMSC: DM/non-DM: n = 94/66, IRR = 1.57, P = 0.005). By Cox regression analysis, the risk of developing overall skin cancer or NMSC was significantly higher after adjusting for sex, comorbidities, and overall diseases with immunosuppression status (overall: adjusted hazard ratio [AHR] = 1.46, P = 0.01; NMSC: AHR = 1.6, P = 0.003). Other significant risk factors were older males for skin cancer (overall: AHR = 1.68, P = 0.001; NMSC: AHR = 1.59, P = 0.004; melanoma: AHR = 3.25, P = 0.04), chronic obstructive pulmonary disease for NMSC (AHR = 1.44, P = 0.04), and coronary artery disease for melanoma (AHR = 4.22, P = 0.01). The risk of developing melanoma was lower in the DM cohort than in the non-DM cohort, but without significance (AHR = 0.56, P = 0.28; DM/non-DM: n = 5/10). The incidence rate and risk of developing overall skin cancer, including NMSC, was significantly higher in older adults with DM. Other significant risk factors for older adults with DM were males for NMSC and melanoma, chronic obstructive pulmonary disease for NMSC, and coronary artery disease for melanoma.

Subsite-specific association of DEAD box RNA helicase DDX60 with the development and prognosis of oral squamous cell carcinoma.

The clinical significance and biological function of DEXD/H box helicase 60 (DDX60) in oral cancer remains unknown. Herein, we evaluated the association of DDX60 expression with tumorigenesis and the prognosis of oral squamous cell carcinoma (OSCC). DDX60 expression was examined by immunohistochemistry on tissue microarray slides of 494 OSCC patients, including 180 buccal mucosal SCC (BMSCC), 241 tongue SCC (TSCC), and 73 lip SCC (LSCC) patients. DDX60 expression was significantly increased in all three subsites of OSCC compared to its expression in tumor adjacent normal tissues. However, its association with tumorigenesis was specific to the oral cavity subsite after the stratification of betel quid chewing, smoking, and drinking. Among OSCC patients, higher levels of DDX60 expression were associated with the male gender, a well-differentiated tumor, advanced stage of disease, and a large tumor size with subsite specific features. LSCC patients with high DDX60 expression levels showed shorter disease-specific survival, particularly those with moderately or poorly differentiated tumors. Additionally, TSCC or OSCC patients with high DDX60 expression showed a poor disease-free survival (DFS), particularly those with moderately or poorly differentiated tumors. Therefore, DDX60 is a novel and unfavorable biomarker for tumorigenesis and prognosis of OSCC in a subsite-specific manner.

The involvement of mitochondrial apoptotic pathway in eugenol-induced cell death in human glioblastoma cells.

Eugenol, a natural phenolic constituent of clove oil, has a wide range of applications in medicine as a local antiseptic and anesthetic. However, the effect of eugenol on human glioblastoma is unclear. This study examined whether eugenol elevated intracellular free Ca(2+) levels ([Ca(2+)]i) and induced apoptosis in DBTRG-05MG human glioblastoma cells. Eugenol evoked [Ca(2+)]i rises which were reduced by removing extracellular Ca(2+). Eugenol-induced [Ca(2+)]i rises were not altered by store-operated Ca(2+) channel blockers but were inhibited by the PKC inhibitor GF109203X and the transient receptor potential channel melastatin 8 (TRPM8) antagonist capsazepine. In Ca(2+)-free medium, pretreatment with the endoplasmic reticulum Ca(2+) pump inhibitor thapsigargin (TG) or 2,5-di-tert-butylhydroquinone (BHQ) abolished eugenol-induced [Ca(2+)]i rises. The phospholipase C (PLC) inhibitor U73122 significantly inhibited eugenol-induced [Ca(2+)]i rises. Eugenol killed cells which were not reversed by prechelating cytosolic Ca(2+) with 1,2-bis(2-aminophenoxy) ethane-N,N,N',N'-tetraacetic acid-acetoxymethyl ester (BAPTA-AM). Eugenol induced apoptosis through increasing reactive oxygen species (ROS) production, decreasing mitochondrial membrane potential, releasing cytochrome c and activating caspase-9/caspase-3. Together, in DBTRG-05MG cells, eugenol evoked [Ca(2+)]i rises by inducing PLC-dependent release of Ca(2+) from the endoplasmic reticulum and caused Ca(2+) influx possibly through TRPM8 or PKC-sensitive channels. Furthermore, eugenol induced the mitochondrial apoptotic pathway.

Effect of melamine on [Ca(2+)]i and viability in PC3 human prostate cancer cells.

Melamine is thought to be an endocrine disrupter that affects physiology in cells. This study examined the effect of melamine on cytosolic free Ca(2+) concentrations ([Ca(2+)]i) and viability in PC3 human prostate cancer cells. Melamine evoked [Ca(2+)]i rises concentration-dependently. Melamine-evoked Ca(2+) entry was inhibited by nifedipine, econazole, SKF96365, GF109203X and phorbol 12-myristate 13 acetate. In Ca(2+)-free medium, treatment with the endoplasmic reticulum Ca(2+) pump inhibitor thapsigargin inhibited melamine-evoked [Ca(2+)]i rise. Conversely, treatment with melamine abolished thapsigargin-evoked [Ca(2+)]i rise. Inhibition of phospholipase C with U73122 did not alter melamine-evoked [Ca(2+)]i rise. Melamine at 500-800µM decreased cell viability, which was not reversed by pretreatment with the Ca(2+) chelator 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid-acetoxymethyl ester (BAPTA/AM). Collectively, our data suggest that in PC3 cells, melamine induced [Ca(2+)]i rises by evoking phospholipase C-independent Ca(2+) release from the endoplasmic reticulum, and Ca(2+) entry via protein kinase C-regulated store-operated Ca(2+) entry. Melamine also caused Ca(2+)-independent cell death.