The Contribution of Double-strand Break Repair Radiation Sensitive Protein 51 Genotypes to Lung Cancer in Taiwan.

BACKGROUND/AIM: Numerous studies have reported the over-expression of the radiation-sensitive protein 51 (RAD51) in various types of cancer. However, the role of RAD51 genotypes in lung cancer remains largely unknown. This study aimed to assess the impact of the common variant RAD51 rs1801320 (G-135C) genotypes on the risk of lung cancer in Taiwan. MATERIALS AND METHODS: The contribution of RAD51 rs1801320 genotypes to lung cancer risk was investigated in a cohort comprising 358 lung cancer patients and 716 age- and sex-matched healthy controls, utilizing polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methodology. RESULTS: The analysis revealed that among the control subjects, the percentages of GG, CG, and CC genotypes of RAD51 rs1801320 were 73.2%, 24.3%, and 2.5%, respectively. Among the lung cancer patients, these percentages were 71.0%, 25.1%, and 3.9%, respectively (p for trend=0.4075). Allelic frequency distributions showed no significant association between the C allele of RAD51 rs1801320 and lung cancer risk determination (p=0.2987). Specifically, the RAD51 rs1801320 CC genotypes were associated with an elevated risk of lung cancer among males [adjusted odds ratio (aOR)=2.28, 95% confidence interval (95%CI)=1.03-4.87] and smokers (aOR=2.93, 95%CI=1.23-5.87), but not among females and non-smokers. CONCLUSION: The RAD51 rs1801320 CC genotype was identified as a risk factor for elevated lung cancer risk in males and smokers. This genotype may serve as a molecular biomarker at the DNA level for early detection and prediction of lung cancer in Taiwan.

Association of Matrix Metalloproteinase-1 Promoter Polymorphisms With Asthma Risk.

BACKGROUND/AIM: Matrix metalloproteinase-1 (MMP-1) expression has been documented as an influential contributor to the intricate milieu of allergic airway inflammation, tissue remodeling, and the exacerbation of asthma's severity. However, the genetic role underlying MMP-1 in the context of asthma has remained enigmatic, with its full implications yet to be unveiled. Considering this, our research was designed to investigate the association of MMP-1 -1607 rs1799750 and the propensity for asthma severity. PATIENTS AND METHODS: As a case-control investigation, our study enrolled 198 individuals diagnosed with asthma and age- and sex-matched 453 non-asthmatic controls. The genotypes of MMP-1 rs1799750 were determined utilizing the polymerase chain reaction-restriction fragment length polymorphism methodology. RESULTS: The frequency distributions of 2G/2G, 1G/2G and 1G/1G genotypes at MMP-1 rs1799750 were 49, 42.9, and 8.1%, respectively, among the patients with asthma. This pattern was not different from that of controls (43.7, 46.8, and 9.5%, respectively) (p for trend=0.4486). The allelic frequency pertaining to the variant 1G allele within the asthma group was 29.5%, with a non-significant disparity compared to the 32.9% in the control group (p=0.2596). Noticeably, there was a positive association between MMP-1 rs1799750 2G/1G and 1G/1G genotypes with asthma severity (p=0.0060). CONCLUSION: Our research indicated that the presence of MMP-1 rs1799750 1G allele might not be the sole arbiter of an individual's susceptibility to asthma, yet its potential to function as a discerning prognostic marker for the severity of asthma emerged as a noteworthy finding deserving attention and further exploration.

The Contribution of DNA Ligase 4 Genetic Variations to Taiwanese Lung Cancer.

BACKGROUND/AIM: Impaired non-homologous end-joining DNA repair capacity may have a significant role in maintaining genome integrity and triggering carcinogenesis. However, the specific impact of DNA ligase 4 (Lig4) genotypes remains unclear. This study aimed to assess the contribution of Lig4 genotypes to the risk of developing lung cancer. MATERIALS AND METHODS: Polymerase chain reaction-restriction fragment length polymorphism analysis was used to examine the genotypes of Lig4 rs1805388, and their association with lung cancer risk was evaluated in a case-control study consisting of 358 lung cancer cases and 716 age- and sex-matched cancer-free control subjects. RESULTS: The distribution of CC, CT, and TT genotypes for Lig4 rs1805388 among the cases was 45.0%, 41.6%, and 13.4%, respectively, compared to 58.0%, 36.3%, and 5.7% among the controls (p for trend=1.98×10-6). Allelic analysis indicated that individuals carrying the T-allele for Lig4 rs1805388 had a 1.66-fold higher risk of developing lung cancer compared to those carrying the wild-type C-allele [95% confidence interval (CI)=1.36-2.02, p=4.04×10-7]. Moreover, a significant interaction was observed between the Lig4 rs1805388 genotype and smoking status (p=1.32×10-7). CONCLUSION: These findings suggest that the CT and TT variant genotypes of Lig4 rs1805388, combined with cigarette smoking, may contribute to a higher risk of developing lung cancer.

Genetic variants in miR-145 gene are associated with the risk of asthma in Taiwan.

Asthma is a chronic airway inflammation disease and the diagnosis and treatment strategies remain difficult. MicroRNAs play important roles in many biological and pathological processes including asthma development. There is no study confirming the contribution of genetic variants in miR-145 to asthma etiology. We hypothesize that single nucleotide polymorphisms (SNPs) in the promoter region of miR-145 may be associated with the risk of asthma in Taiwanese. We used a case-control study to test this hypothesis. In 198 asthma patients and 453 healthy controls, the genotypes of miR-145 rs4705342 and rs4705343 were determined, and the associations of miR-145 genotypes with asthma risk and severity were evaluated. The distribution of miR-145 rs4705342 genotypes between asthma patients and non-asthmatic control groups were significantly different (p = 0.0187). In multivariable logistic regression analysis, compared with the wild-type TT genotype, individuals carrying the variant genotypes had progressively decreased risks of asthma: the odds ratio (OR) for the heterogeneous variant genotype (CT) and homozygous variant genotype (CC) was 0.77 (95% CI 0.55-1.10, p = 0.1788) and 0.41 (95% CI 0.21-0.79, p = 0.0102), respectively (p for trend = 0.0187). In allelic test, the C allele was associated with a 31% reduced risk of asthma (OR = 0.69, 95% CI 0.53-0.90, p = 0.0070). In addition, the rs4705342 variant genotypes were correlated with the symptom severity (p = 3 × 10-5). Furthermore, the variant genotypes correlated with lower miR-145-5p expression level in serum (p = 0.0001). As for rs4705343, there was no differential distribution of genotypes between cases and controls. Our data provide evidence for miR-145 rs4705342 to serve as a novel biomarker for asthma risk prediction.

Significant Association of Chitinase 3-like 1 Genotypes to Asthma Risk in Taiwan.

BACKGROUND/AIM: Chitinase 3-like 1 (CHI3L1) is overexpressed in asthma, and negatively associated with forced expiratory volume in the first second. This study aimed at evaluating whether CHI3L1 genotypes affect asthma risk. MATERIALS AND METHODS: The blood samples of 198 asthma patients and 453 control subjects were collected, and the genotypic patterns of CHI3L1 -131C/G (rs4950928) and -247G/A (rs1262491437) were examined. RESULTS: The percentages of CG and GG at CHI3L1 -131C/G were 32.8% and 7.6% among the asthma cases, respectively, significantly higher than the 23.8% and 3.1% among the non-asthmatic healthy subjects (p for trend=0.0009). The allelic frequency distribution analysis showed that the G allele at CHI3L1 - 131C/G conferred a significantly higher asthma risk than the wild-type C allele (p<0.0001). The genotypic and allelic frequency analyses for CHI3L1 -247G/A did not show any significant difference. CONCLUSION: The G allele at CHI3L1-131C/G serves as a biomarker in determining personal susceptibility to asthma in Taiwan.

The association of matrix metalloproteinas-2 promoter polymorphisms with lung cancer susceptibility in Taiwan.

Matrix metalloproteinases-2 (MMP2) has been reported to be overexpressed in various types of cancer. However, the contribution of various genotypes of MMP2 to lung cancer is controversial and not yet been examined in Taiwan. Therefore, in the current study, we investigated the association of MMP2 genotypes with lung cancer risk among Taiwanese. In this hospital-based, case-control study, 358 lung cancer patients and 716 age- and gender-matched healthy controls were recruited, and the genotypic distributions of MMP2-1306 and MMP2- 735 were determined. Then, their association with lung cancer was evaluated, and their interaction with personal smoking status was also examined via stratification analysis. The results showed that the percentages of variant CT and TT at MMP2-1306 were 17.3% and 1.7% among the lung cancer patients, respectively, much lower than those of 28.7% and 2.4%, respectively, among the healthy controls (P for trend = 0.0001). The allelic frequency distribution analysis showed that the variant T allele at MMP2-1306 conferred a statistically significantly lower lung cancer risk than the wild-type C allele (adjusted odds ratio = 0.54, 95% confidence interval = 0.41-0.72, P = 0.0001). There was an obvious effect of MMP2-1306 genotype on lung cancer risk among the subpopulations of ever smokers but not nonsmokers. As for the genotypes of MMP2-735, there was no such differential distribution in the aspects of genotypic or allelic frequencies, or combinative effects with smoking status. The genotypes of MMP2-1306 may act as a biomarker in determining personal susceptibility to lung cancer in Taiwan. The contribution of MMP2 genotypes alone and its joint effects with personal cigarette smoking habit on lung cancer susceptibility should be taken into consideration of the clinical practices for early detection and prediction of lung cancer in Taiwan.

The Association of MMP-11 Promoter Polymorphisms With Susceptibility to Lung Cancer in Taiwan.

BACKGROUND/AIM: Matrix metalloproteinases-11 (MMP-11) overexpression has been reported in various types of cancer including lung cancer. We aimed to examine the contribution of MMP-11 genotypes to lung cancer risk. MATERIALS AND METHODS: In this case-control study, the MMP-11 rs738791, rs2267029, rs738792 and rs28382575 genotypes were determined among 358 lung cancer patients and 716 age- and gender-matched healthy control Taiwanese. RESULTS: The percentages of rs738791 CT and TT were 50.6% and 9.2% in the case group, slightly higher than 48.5% and 8.1% in the control group (p for trend=0.5638). The allelic analysis showed that the rs738791 T allele did not confer lung cancer risk compared with the C allele. Similarly, there was no association between rs2267029, rs738792 or rs28382575 and lung cancer risk. There was no joint effect of MMP-11 genotypes among ever smokers or non-smokers. CONCLUSION: The genotypes of MMP-11 play a minor role in determining lung cancer risk in Taiwan.

Contribution of Caspase-8 Genotypes to Colorectal Cancer Risk in Taiwan.

BACKGROUND/AIM: The aim of this study was to examine the role of caspase-8 rs3834129 polymorphism on colorectal cancer (CRC) risk in Taiwanese CRC patients and healthy controls. MATERIALS AND METHODS: The caspase-8 rs3834129 (-652 6N insertion/deletion) polymorphic genotypes were analyzed in 362 patients with CRC and the same number of age- and gender-matched healthy subjects. The interaction of caspase-8 rs3834129 genotypes with personal behaviors and clinicopathological features were also examined. RESULTS: The percentage of variants ID and DD for caspase-8 rs3834129 genotype were 37.6 and 5.8% in CRC group and 39.0 and 6.6% in the control group, respectively (p for trend=0.7987). The allelic frequency distribution analysis showed that caspase-8 rs3834129 D allele conferred a non-significant lower susceptibility for CRC compared with I allele (OR=0.92, 95%CI=0.74-1.20, p=0.5063). There was no obvious link between caspase-8 rs3834129 genotype and CRC risk among ever-smokers, non-smokers, non-alcohol drinkers or alcohol drinkers. No statistically significant correlation was observed between caspase-8 rs3834129 genotypic distribution and age, gender, tumor size, location or metastasis status. CONCLUSION: Overall, caspase-8 rs3834129 genotypes may not serve as predictors for CRC risk or prognosis.

The Contribution of MMP-7 Promoter Polymorphisms to Taiwan Lung Cancer Susceptibility.

BACKGROUND/AIM: Matrix metalloproteinase-7 (MMP-7) plays an important role in metastasis behavior of cancer cells, and overexpression of MMP-7 has been associated with poor prognosis in non-small cell lung cancer. However, the contribution of various genotypes of MMP-7 has not yet been investigated in lung cancer in Taiwan. Therefore, this study aimed to investigate the association of MMP-7 genotypes with lung cancer risk among the Taiwanese. MATERIALS AND METHODS: In this hospital-based case-control study, genotypes and distributions at two promoter sites of MMP-7, A-181G and C-153T, were determined, and their association with lung cancer risk in Taiwan was evaluated among 358 lung cancer patients and 716 age- and gender-matched healthy control individuals. In addition, the interaction of MMP-7 genotypes and smoking status were also examined. RESULTS: The percentages of variant AG and GG at MMP-7 A-181G in the lung cancer group were similar to the control group (12.8% and 2.3% vs. 11.3% and 1.5%, respectively; ptrend=0.5294). The allelic frequency distribution analysis showed that the variant G allele at MMP-7 A-181G conferred non-significant elevated lung cancer risk compared to the wild-type A allele [odds ratio (OR)=1.18, 95% confidence interval (CI)=0.85-1.66, p=0.2289]. As for the genotypes of MMP-7 C-153T, all the studied Taiwanese population was of CC genotype. Furthermore, there was no obvious joint effect of MMP-7 A-181G genotype and smoking status on the lung cancer risk. No statistically significant correlation was observed between MMP-7 A-181G genotype distributions and gender. CONCLUSION: There was no evidence that the genotypes of MMP-7 A-181G may act as a biomarker in determining personal susceptibility to lung cancer in Taiwan.

Contribution of Murine Double Minute 2 Genotypes to Colorectal Cancer Risk in Taiwan.

BACKGROUND/AIM: The genomic role of human mouse double minute 2 (MDM2) in colorectal cancer (CRC) is unclear, therefore, our study aimed to evaluate the contribution of MDM2 genotype to the risk of CRC in Taiwan. MATERIALS AND METHODS: In this case-control study, MDM2 SNP309 T to G (rs2279744) genotypes were determined and their association with CRC risk were investigated among 362 patients with CRC and 362 age- and gender-matched healthy controls in central Taiwan. In addition, the interaction of MDM2 SNP309 genotypes with personal behaviors and clinicopathological features were also examined. RESULTS: The percentage of variant GG for the MDM2 SNP309 genotype was 30.9% in the CRC group and 24.0% in the control group, respectively (odds ratio (OR)=1.78, 95% confidence interval (CI)=1.25-2.86, p=0.0057). The allelic frequency distribution analysis showed that the variant G allele of MDM2 SNP309 conferred a significantly increased susceptibility to CRC compared with the wild-type T allele (OR=1.32, 95% CI=1.14-1.69, p=0.0062). As for the gene-lifestyle interaction, there was an obvious joint effect of MDM2 SNP309 GG genotype on the risk of CRC among ever-smokers and non-alcohol drinkers, but not non-smoker or alcohol drinker subgroups. No statistically significant correlation was observed between MDM2 SNP309 genotypic distributions and age, gender, tumor size, location or metastasis status. CONCLUSION: The genotypes of MDM2 SNP309 may allow forr early detection of and predictor for CRC risk, especially among smokers and non-alcohol drinkers, but not for prognosis. The combined effects of MDM2 SNP309 and other genes (such as matrix metalloproteinases) on CRC susceptibility and prognosis, should also be taken into consideration in the era of precision medicine.

Contribution of Double-strand Break Repair Gene Nijmegen Breakage Syndrome 1 Genotypes, Gender Difference and Smoking Status to Taiwanese Lung Cancer.

BACKGROUND/AIM: Nijmegen breakage syndrome 1 (NBS1) is a component of MRE11/RAD50/NBS1 complex (MRN) that plays a critical role in the cellular response to DNA damage and maintenance of chromosomal integrity. Failure in DNA damage response affects the level of cell survival, increases the frequency of gene mutation or chromosomal instability and other cellular phenotypic abnormalities, which are the important mechanisms of carcinogenesis. However, the contribution of variant NBS1 genotypes to lung cancer is not known. The current study aimed to evaluate the contribution of the common variant NBS1 Glu185Gln (rs1805794, E185Q) genotypes to the risk of lung cancer. MATERIALS AND METHODS: The contributions of the NBS1 Glu185Gln genotypes to lung cancer risk were investigated among 358 patients with lung cancer and 716 age- and gender-matched healthy controls by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). RESULTS: GG, CG and CC NBS1 Glu185Gln genotype percentages were 45.2%, 43.9% and 10.9% in the patient group and 46.1%, 45.1% and 8.8% in the non-cancer control group, respectively (p for trend=0.5423). Analysis of allelic frequency distributions showed that the C allele of NBS1 Glu185Gln did not increase lung cancer susceptibility (p=0.4916). Interestingly, the CC genotypes at NBS1 Glu185Gln enhanced the risk of lung cancer among the males adjusted odds ratio (aOR)=1.85, 95% confidence interval (CI)=1.12-2.83 and among the smokers (aOR=1.76, 95% CI=1.09-2.64) but not among the females and non-smokers. CONCLUSION: The CC genotype of NBS1 Glu185Gln may increase lung cancer risk only for males and smokers and may serve as a practical marker for early detective and predictive purposes of lung cancer.

The Contribution of Matrix Metalloproteinase-1 Genotypes to Hepatocellular Carcinoma Susceptibility in Taiwan.

BACKGROUND/AIM: Metalloproteinases (MMPs) are a family of proteases which have been shown to be overexpressed in various types of cancers. However, the contribution of MMP1 genotype to hepatocellular carcinoma (HCC) has not been well studied. This study aimed to evaluate the contribution of MMP1 promoter 1607 genotype to the risk of HCC in Taiwan, where HCC incidence is relatively high in the world. MATERIALS AND METHODS: In this case-control study, MMP1 genotype and its interaction with consumption of cigarettes and alcohol in determining HCC risk was investigated among 298 HCC patients and 889 age- and gender-matched healthy controls. RESULTS: The percentages of ever smokers and ever alcohol drinkers were much higher in the case group than in the control group. The percentages of 2G/2G, 1G/2G and 1G/1G for MMP1 promoter 1607 genotype were 37.2%, 38.3% and 24.5% in the HCC group and 34.8%, 44.0% and 21.2% in the control group, respectively (p for trend=0.2048). The allelic frequency distribution analysis showed the variant 1G allele of MMP1 promoter 1607 conferred similar HCC susceptibility as the wild-type 2G allele (odds ratio (OR)=1.01, 95% confidence interval (CI)=0.84-1.22, p=0.8735). As for the gene-lifestyle interaction, there was an obvious protective effect of MMP1 promoter 1607 1G allele on the risk of HCC among non-smokers, but not non-smokers, even alcohol drinkers or non-drinkers. CONCLUSION: The 1G allele of MMP1 promoter 1607 may have a protective effect on HCC risk for non-smokers in Taiwan and further validations are needed in other population groups.

Contribution of DNA Repair Xeroderma Pigmentosum Group D Genotypes to Colorectal Cancer Risk in Taiwan.

BACKGROUND/AIM: It has been previously proposed that genetic variations on DNA repair genes confer susceptibility to cancer and the DNA repair gene Xeroderma Pigmentosum Group D (XPD) is thought to play the role of a helicase during excision repair and transcription. We investigated three genotypes of XPD, at promoter -114 (rs3810366), Asp312Asn (rs1799793) and Lys751Gln (rs13181), regarding their association with colorectal cancer susceptibility in a Taiwanese population. MATERIALS AND METHODS: In total, 362 patients with colorectal cancer and 362 gender- and age-matched healthy controls were genotyped by polymerase chain reaction-based restriction fragment length polymorphism (PCR-RFLP), and their XPD genotypes' association with colorectal cancer risk was investigated. RESULTS: The genotypes of XPD Asp312Asn (p=0.2493), Lys751Gln (p=0.7547) and promoter -114 (p=0.8702), were not associated with susceptibility for colorectal cancer. The Chi-square test revealed that the variant alleles of XPD Asp312Asn, Lys751Gln and promoter -114 was not associated with susceptibility for colorectal cancer either [p=0.1330, 0.3888 and 0.8740; odds ratio (OR)=1.20, 0.83 and 0.98; 95% confidence interval (95%CI)=0.95-1.52, 0.54-1.27 and 0.80-1.21, respectively]. The risk of A/G and A/A genotypes have no association with cancer risk among non-alcohol drinkers (OR=1.24, 95%, CI=0.90-1.72, p=0.2103) or alcohol drinkers (OR=1.51, 95% CI=0.64-3.55, p=0.4648). There exists no obvious contribution of XPD genotypes to tumor size (p=0.3531), location (p=0.3006) and lymph node metastasis (p=0.1061). CONCLUSION: Asp312Asn, Lys751Gln and promoter -114 of the XPD gene were not found to be adequate predictive markers for colorectal cancer risk in Taiwan.

Contribution of Interleukin-4 Genotypes to Lung Cancer Risk in Taiwan.

AIM: Lung cancer is the leading cause of cancer-related death worldwide. Interleukin-4 (IL-4) is a typical pleiotropic T helper 2 cytokine involved in immunology during carcinogenesis. The present study aimed at evaluating the contribution of IL-4 promoter T-1099G (rs2243248), C-589T (rs2243250), C-33T (rs2070874) genetic polymorphisms to the risk of lung cancer in Taiwan. MATERIALS AND METHODS: The contributions of the promoter IL-4 polymorphic genotypes to lung cancer risk were investigated in 358 lung cancer patients and 716 age- and gender-matched healthy controls. In addition, the interaction between IL-4 and individual smoking status was also evaluated. RESULTS: The percentages of CC, CT and TT for IL-4 C-589T genotypes were differentially represented as 69.0%, 26.5% and 4.5% in the lung-cancer patient group and 61.3%, 30.4% and 8.3% in the non-cancer control group, respectively (p=0.0156). The TT genotype carriers were of lower risk for lung cancer (odds ratio (OR)=0.48, 95% confidence interval (CI)=0.27-0.86, p=0.0106) than the CC genotype carriers. We also analyzed the allelic frequency distributions and the results showed that the T allele of IL-4 C-589T conducted a protective effect on lung cancer susceptibility (p=0.0022). On the contrary, there was no difference in the distribution of genotypic or allelic frequencies among patients and controls for the IL-4 promoter T-1099G and C-33T. CONCLUSION: The TT genotype of IL-4 C-589T compared to the CC wild-type genotype may have a protective effect on lung cancer risk in Taiwan and may serve as an early detection and prediction marker.

Tumor Necrosis Factor-α Genotypes Are Associated with Hepatocellular Carcinoma Risk in Taiwanese Males, Smokers and Alcohol Drinkers.

AIM: Hepatocellular carcinoma (HCC), the fifth most common cancer worldwide, has high prevalence and mortality rates in Taiwan. Tumor necrosis factor-α (TNFα), an important proinflammatory cytokine, is involved in multiple physiological and pathogenic phenomena that lead to the destruction and dysregulation of tissues. The present study aimed to evaluate the contribution of TNFA genotype, together with cigarette smoking and alcohol drinking lifestyle to the risk of HCC. MATERIALS AND METHODS: In this hospital-based case-control study, association of TNFA single-nucleotide polymorphisms -1031T/C, -863C/A, -857T/C, -308G/A and +489A/G, with HCC risk were examined in 298 patients with HCC and 889 age- and gender-matched healthy controls. RESULTS: The percentages of AA, AG and GG TNFA -308G/A were 6.4%, 18.1% and 75.5% in the HCC patient group and 2.0%, 16.0% and 82.0% in the non-cancer control group, respectively. The AA and AG genotypes were associated with 3.42- and 1.23-fold higher odds of HCC than the GG genotype (95% confidence interval=1.76-6.63 and 0.87-1.74, respectively). No such significant difference was found for other polymorphic sites. We further stratified the populations by gender, cigarette smoking and alcohol drinking status to investigate their combined contributions with TNFA -308G/A genotype to HCC risk. The results showed that the AA and AG genotypes of TNFA -308G/A increased HCC susceptibility which was obvious among males, smokers, and alcohol drinkers, but not females, non-smokers, or non-drinkers (p=0.0003, 0.0003, 0.0014, 0.6127, 0.7442 and 0.3010, respectively). CONCLUSION: Our results suggest that the AA and AG polymorphism of TNFA -308G/A genotypes associated with HCC risk in Taiwan, particularly among males, smokers and alcohol drinkers.

Protective Effects of Pyridoxamine Against UVC-induced Programmed Cell Death in HaCaT Cells.

BACKGROUND: Exposure to ultraviolet (UV) light is closely related to human diseases, such as skin cancer, due to irreversible injuries to the skin cells. The UV-induced DNA damage and programmed cell death are important determinants for skin carcinogenesis. The aim of the present study was to investigate the anti-ultraviolet-C (UVC) effects of pyridoxamine in human keratinocyte HaCaT cells and its mechanisms of action. RESULTS: UVC-induced programmed cell death in HaCaT cells was abrogated by treated the cells immediately after UVC irradiation with 40, 80 and 160 µM of pyridoxamine. Monitoring the UVC-induced-specific reactive oxygen species, we found that 20, 40, 80 and 160 µM of pyridoxamine was also effective in suppressing the induction of reactive oxygen species by UVC. CONCLUSION: Overall, our results provided evidence showing that pyridoxamine was effective in protecting HaCaT cells from UVC-induced programmed cell death and may be a potential anti-UVC agent in life and clinical practice.

Circulating anti-cyclic citrullinated peptide antibody in patients with rheumatoid arthritis and chronic obstructive pulmonary disease.

Anti-cyclic citrullinated peptide (anti-CCP) antibody is highly specific for diagnosing rheumatoid arthritis (RA). Cigarette smoking is a lifestyle and environmental factor associated with anti-CCP production and is strongly associated with chronic obstructive pulmonary disease (COPD). This study assessed levels of anti-CCP antibodies and rheumatoid factor (RF) among patients with RA and COPD. The study sample comprised 63 patients with RA and 70 patients with COPD, all of whom underwent assessment of anti-CCP antibody and RF levels. Testing revealed that 54.2% of RA patients and 0% of COPD patients were positive for anti-CCP antibodies. Additionally, 82.5% of RA patients and 42% of COPD patients were positive for RF. Among RA patients, levels of anti-CCP antibodies were higher among smokers than among nonsmokers (242.7 ± 128.3 vs. 68.1 ± 112.1, P < 0.001). COPD patients had low titers of RF but were negative for anti-CCP antibodies. The presence of anti-CCP antibodies was a reliable serologic marker in RA diagnosis and was associated with cigarette smoking.

Acute appendicitis presenting as unusual left upper quadrant pain.

Appendicitis is the most common abdominal disease that requires surgery in the emergency ward. It usually presents as right lower quadrant pain, but may rarely present as left upper quadrant (LUQ) pain due to congenital anatomical abnormalities of the intestine. We report a patient who complained of persistent LUQ abdominal pain and was finally diagnosed by computed tomography (CT) as congenital intestinal malrotation complicated with acute appendicitis. It is important to include acute appendicitis in the differential diagnosis of patients who complain of LUQ abdominal pain. Abdominal CT can provide significant information that is useful in preoperative diagnosis and determination of proper treatment.

Baicalin scavenges reactive oxygen species and protects human keratinocytes against UVC-induced cytotoxicity.

Long-term exposure to solar ultraviolet (UV) radiation can cause multiple skin disorders, including skin cancer. Protection against UV-induced damage is, therefore, a worldwide concern. Baicalin, a major component of traditional Chinese medicine Scutellaria baicalensis, has been reported to have antioxidant and cytostatic effects on normal epithelial and normal peripheral blood and myeloid cells. In the current study, we examined whether baicalin could also effectively protect human keratinocytes from damaging short-wave UVC irradiation. Baicalin-scavenged reactive oxygen species increased within 2 h after UVC radiation. Baicalin also abrogated UVC-induced apoptosis. In addition, we identified the major products after UVC radiation with T4 UV endonuclease, finding that baicalin prevented cyclobutane pyrimidine dimer formation induced by UVC. Furthermore, baicalin also prevented formation of oxidative adducts induced by UVC. Our results demonstrated the utility of baicalin in assessing the potential contribution of traditional Chinese medicinal agents in therapy of UVC-induced genomic damage to skin and suggest potential application of these agents as pharmaceuticals in prevention of solar-induced skin damage.

Amentoflavone induces cell-cycle arrest and apoptosis in MCF-7 human breast cancer cells via mitochondria-dependent pathway.

Amentoflavone, isolated from an ethyl acetate extract of the whole plant of Selaginella tamariscina, a traditional herb, may exhibit antitumor activity. The aim of this study was to investigate the anticancer mechanism(s) of amentoflavone, such as mitochondria-mediated apoptotic cell death, in typical breast cancer MCF-7 cells. Cells treated with amentoflavone exhibited a series of cellular alterations related to apoptosis, including DNA and nuclear fragmentation, and de-regulation of intracellular reactive oxygen species (ROS) and calcium. In addition, markers of mitochondrial-mediated apoptosis, including the reduction of mitochondrial inner-membrane potential, the release of cytochrome c from mitochondria, and activation of caspase 3, were observed. In conclusion, our results present, to our knowledge, the first evidence that amentoflavone induces apoptosis of MCF-7 breast cancer cells, and that this is closely related to mitochondrial dysfunction. Amentoflavone may be a potential therapeutic agent for breast cancer treatment.