Differential Effect of ITE on the Aryl Hydrocarbon Receptor Signaling in Breast Cancer Tissue: A Histopathological Study / Efecto Diferencial de ITE en la Señalización del Receptor de Hidrocarburo de Arilo en Tejido de Cáncer de Mama: Un Estudio Histopatológico

SUMMARY: Aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that is highly expressed in various types of cancers including breast cancer. However, the role of AhR with its endogenous ligand 2-(1'H-indole-3'-carbonyl)-thiazole-4-carboxylic acid methyl ester (ITE) on the progression of breast cancer remains poorly understood. We aimed to investigate cell proliferation and migration states in breast cancer after activating AhR with the endogenous ligand ITE. Breast cancer tissue was evaluated by cell lines, immunohistochemistry, reverse transcription-polymerase chain reaction, cell proliferation, flow cytometry, migration assays and western blot techniques. We found that AhR was widely expressed in breast cancer tissues and metastasis lymph node tissues, but not in normal tissues. The expression AhR was independent between the age, grades and TNM classifications for breast cancer tissues. ITE treatment significantly induced the activation of AhR in a time-dependent manner in both MCF-7 and T47D breast cancer cell lines. Meanwhile, ITE did not affect the cell migration but significantly suppressed the cell proliferation in estrogen receptor positive (ER+) MCF-7 andT47D cells, which probably attribute to the induction of cell cycle arrest in G1 phase and shortened S phase. Further mechanism study showed that ERK1/2 and AKT signaling were required for the activation of AhR in MCF-7 cells. These data suggest that AhR is a potential new target for treating patients with breast cancer. ITE may be more potentially used for therapeutic intervention for breast cancer with the kind of ER(+).

El receptor de hidrocarburo de arilo (AhR) es un factor de transcripción activado por ligando que se expresa en gran medida en varios tipos de cáncer, incluido el cáncer de mama. Sin embargo, el papel de AhR con su ligando endógeno 2- (1'H-indol-3'-carbonil)-tiazol-4-ácido carboxílico metil éster (ITE) en la progresión del cáncer de mama sigue siendo poco conocido. Nuestro objetivo fue investigar la proliferación celular y los estados de migración en el cáncer de mama después de activar AhR con el ligando endógeno ITE. El tejido de cáncer de mama se evaluó mediante líneas celulares, inmunohistoquímica, reacción en cadena de la polimerasa con transcriptasa inversa, proliferación celular, citometría de flujo, ensayos de migración y técnicas de transferencia Western. Descubrimos que AhR se expresó ampliamente en tejidos de cáncer de mama y en linfonodos con metástasis, pero no en tejidos normales. La expresión AhR fue independiente entre la edad, grados y clasificaciones TNM para tejidos de cáncer de mama. El tratamiento con ITE indujo significativamente la activación de AhR de manera dependiente del tiempo en las líneas celulares de cancer de mama MCF-7 y T47D. Mientras tanto, ITE no afectó la migración celular, pero suprimió significativamente la proliferación celular en células MCF-7 y T47D con receptor de estrógeno positivo (ER+), lo que probablemente se atribuye a la inducción de la detención del ciclo celular en la fase G1 y la fase S acortada. Un estudio adicional del mecanismo mostró que las señales de ERK1/2 y AKT eran necesarias para la activación de AhR en las células MCF-7. Estos datos sugieren que AhR es un nuevo objetivo potencial para el tratamiento de pacientes con cáncer de mama. ITE puede ser utilizado más potencialmente en la intervención terapéutica para el cáncer de mama con el tipo de ER (+).

Effect of superfine powder and aqueous extract of Polygonati Rhizoma on rats with natural perimenopausal syndrome / 中国中药杂志

This study aims to examine the effect of superfine powder and aqueous extract of Polygonati Rhizomaon on natural perimenopausal syndrome in rats and explore the underlying mechanism. To be specific, a total of 60 female SD rats(14-15 months old) with estrous cycle disorder were screened by the vaginal smear and randomized into model control group, β-estradiol 3-benzoate group(0.1 mg·kg~(-1)), superfine powder of Polygonati Rhizoma group(0.25, 0.5 g·kg~(-1)) and aqueous extract of Polygonati Rhizoma group(0.25, 0.5 g·kg~(-1)), and another 10 female SD rats(14-15 months old) were selected as the youth control group. The administration lasted 6 weeks. Then the perimenopausal syndrome-related indexes such as body temperature, microcirculatory blood flow of face and ear, vertigo period, salivary secretion, grip force, and bone strength were determined and open field test was conducted. The immune system-related indexes such as the wet weight and index of thymus and spleen, percentage of T lymphocytes and subgroups in peripheral blood, and hematological indexes were measured. In addition, the ovary-related indexes such as estrous cycle, the wet weight and index of uterus and ovary, ovarian tissue morphology, and cell apoptosis were determined. Moreover, hypothalamus-pituitary-ovary axis(HPO)-related indexes such as serum sex hormone levels, cytochrome P450 family 11 subfamily A member 1(CYP11A1), cytochrome P450 family 19 subfamily A member 1(CYP19A1), and cytochrome P450 family 17 subfamily A member 1(P450 17A1) in ovarian tissue were measured. The results showed that the superfine powder and aqueous extract of Polygonati Rhizoma significantly decreased body temperature(anal, facial and dorsal temperature), microcirculatory blood flow in the ear, and vertigo period, increased salivary secretion, grip force, bone strength, total distance and total speed in the open field test, wet weight and index of thymus and spleen, lymphocyte ratio, CD3~+ level, and CD4~+/CD8~+ ratio, reduced neutrophil number and ratio, estrous cycle disorder ratio, and number of ovarian apoptotic cells, raised wet weight and index of uterus, wet weight of ovary, levels of inhibin B(INHB), estradiol(E_2), anti-müllerian hormone(AMH), and ovarian CYP11A1 and CYP19A1, decreased follicle-stimulating hormone(FSH) and luteinizing hormone(LH) content, and improved ovarian tissue morphology. It is suggested that the superfine powder and aqueous extract of Polygonati Rhizoma can improve the symptoms associated with natural perimenopausal syndrome in rats and enhance ovarian function and immune function. The mechanism is that they regulate HPO axis function by increasing estrogen synthesis.

Schisandra chinensis Oil Attenuates Aristolochic Acid I-Induced Nephrotoxicity in vivo and in vitro / 中国结合医学杂志

OBJECTIVE@#To investigate the protective effects of Schisandra chinensis oil (SCEO) against aristolochic acid I (AA I)-induced nephrotoxicity in vivo and in vitro and elucidate the underlying mechanism.@*METHODS@#C57BL/6 mice were randomly divided into 5 groups according to a random number table, including control group, AA I group, and AA I +SCEO (0.25, 0.5 and 1 g/kg) groups (n=5 per group). Pretreatment with SCEO was done for 2 days by oral administration, while the control and AA I groups were treated with sodium carboxymethyl cellulose. Mice of all groups except for the control group were injected intraperitoneally with AA I (5 mg/kg) from day 3 until day 7. Histopathological examination and apoptosis of kidney tissue were observed by hematoxylin and eosin and TdT-mediated dUTP nick-end labeling (TUNEL) staining, respectively. The levels of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood urea nitrogen (BUN), and serum creatinine (SCr), as well as renal malondialdehyde (MDA), glutathione, r-glutamyl cysteingl+glycine (GSH), and superoxide dismutase (SOD) were analyzed using enzyme-linked immunosorbent assay (ELISA). Expressions of hepatic cytochrome P450 1A1 (CYP1A1), CYP1A2, and nad(p)hquinonedehydrogenase1 (NQO1) were analyzed using ELISA, quantitative real-time polymerase chain reaction (qPCR) and Western blot, respectively. In vitro, SCEO (40 µ g/mL) was added 12 h before treatment with AA I (40 µ mol/mL for 48 h) in human renal proximal tubule cell line (HK-2), then apoptosis and reactive oxygen species (ROS) were analyzed by flow cytometry.@*RESULTS@#SCEO 0.5 and 1 g/kg ameliorated histopathological changes and TUNEL+ staining in the kidney tissues of mice with AA I-induced nephrotoxicity, and reduced serum levels of ALT, AST, BUN and SCr (P<0.01 or P<0.05). SCEO 0.5 and 1 g/kg alleviated the ROS generation in kidney, containing MDA, GSH and SOD (P<0.01 or P<0.05). SCEO 1 g/kg increased the expressions of CYP1A1 and CYP1A2 and decreased NQO1 level in the liver tissues (P<0.01 or P<0.05). Besides, in vitro studies also demonstrated that SCEO 40 µ g/mL inhibited apoptosis and ROS generation (P<0.05 or P<0.01).@*CONCLUSIONS@#SCEO can alleviate AA I-induced kidney damage both in vivo and in vitro. The protective mechanism may be closely related to the regulation of metabolic enzymes, thereby inhibiting apoptosis and ROS production.

Influence of nicotine dependence, current smoking status and gender on CYP1A1, CYP1B1 and CYP2A6 expression in oral squamous cell carcinoma / Influência da dependência nicotínica, parâmetros de consumo de tabaco e gênero na expressão de CYP1A1, CYP1B1 e CYP2A6 em carcinoma de células escamosas oral

Objective: Tobacco smoke is composed of cancer-causing chemicals referred to as carcinogens. These carcinogens are metabolized by the enzymes of the cytochrome P450 (CYP) family. Our objective was to evaluate the correlation of tobacco consumption parameters with CYP1A1, CYP1B1 and CYP2A6 expression using qRT-PCR in samples of oral squamous cell carcinoma (OSCC). Material and Methods: The sample was divided into 2 groups: Cancer (36 subjects) and non-Cancer (12 subjects). The smokers' participants (36) were evaluated regarding their Nicotine dependence (ND) was assessed by the Fagerström test for cigarette dependence (FTCD). Questions regarding tobacco consumption like the number of cigarettes/day (CPD), duration of use, and pack-years were also evaluated. The Mann-Whitney and Spearman correlation tests were used at a significance level of 5%. Results: 48 participants were included, 32 men (66.7%), 36 smokers (75%) and 27 smokers with OSCC (56.3%). Samples of OSCC expressed more CYP1A1, CYP1B1, and CYP2A6. Especially, the CYP1B1 gene was significantly expressed in OSCC samples, regardless gender or tobacco use. No women expressed CYP2A6, as well as, non-smokers did not express the CYP1A1 and CYP2A6 genes. CYP1A1 gene was higher among men (P = 0.021). Conclusion: Lack of exposure to tobacco may justify the absence of CYP1A1 and CYP2A6 expression in non-smokers. The CYP1B1 gene was significantly expressed in the cancer presence despite gender or tobacco use. The assessment of ND and quantification of tobacco consumption are important instruments in monitoring smokers with benign oral lesions and, especially, in the presence of cancer.(AU)

Objetivo: A fumaça do tabaco é composta de substâncias químicas cancerígenas conhecidas como carcinógenos. Esses carcinógenos são metabolizados pelas enzimas da família do citocromo P450 (CYP). Nosso objetivo foi avaliar a correlação dos parâmetros do consumo de tabaco com a expressão de CYP1A1, CYP1B1 e CYP2A6 por qRT-PCR em amostras de carcinoma de células escamosas bucal (CCEB). Material e Métodos: A amostra foi dividida em 2 grupos: Câncer (36 indivíduos) e sem Câncer (12 indivíduos). Os participantes fumantes (36) foram avaliados quanto à dependência nicotínica (DN) pelo teste de Fagerström para dependência de cigarro (TFDC). Questões relacionadas ao consumo de tabaco como número de cigarros / dia (CPD), tempo de uso e anos-maço também foram avaliadas. Os testes de correlação de Mann-Whitney e Spearman foram utilizados com nível de significância de 5%. Resultados: foram incluídos 48 participantes, 32 homens (66,7%), 36 fumantes (75%) e 27 fumantes com CCEB (56,3%). Amostras de CCEB expressaram mais CYP1A1, CYP1B1 e CYP2A6. Especialmente, o gene CYP1B1 foi significativamente expresso em amostras de CCEB, apesar do sexo ou uso de tabaco. Nenhuma mulher expressou CYP2A6, assim como, não fumantes não expressaram os genes CYP1A1 e CYP2A6. O gene CYP1A1 foi maior entre os homens (P = 0,021). Conclusão: A falta de exposição pode justificar a ausência da expressão dos genes CYP1A1 e CYP2A6 entre não fumantes. O gene CYP1B1 foi significativamente expresso na presença de câncer, independentemente do sexo ou do uso de tabaco. A avaliação da DN e a quantificação do consumo de tabaco são importantes instrumentos no acompanhamento de fumantes com lesões bucais benignas e, principalmente, na presença de câncer (AU)

Aryl Hydrocarbon Receptor is Involved in the Proinflammatory Cytokine Response to Cadmium / 生物医学与环境科学（英文）

Objective@#To investigate involvement of the aryl hydrocarbon receptor (AhR) in the immunomodulatory effects of cadmium (Cd).@*Methods@#The effect of Cd on AhR activation ( @*Results@#Cd increased @*Conclusion@#AhR signaling is involved in the lung leukocyte proinflammatory cytokine response to Cd. The relevance of the AhR to the cytokine response to Cd provides new insight into the mechanisms of Cd immunotoxicity.

Inhibitory effect of flavonoids from Scutellariae Radix on human cytochrome P450 1A / 中国中药杂志

This study investigated the inhibitory effect of eight natural flavonoids in Chinese herb Scutellariae Radix on huamn cytochrome P450 1 A(CYP1 A), a key cancer chemo-preventive target. In this study, phenacetin was used as a probe substrate for CYP1 A, while human liver microsomes and recombinant human CYP1 A enzymes were used as enzyme sources. Liquid chromatography-tandem mass spectrometry was used to monitor the formation rates of acetaminophen, the O-deethylated metabolite of phenacetin. The dose-dependent inhibition curves were depicted based on the changes of the formation rates of acetaminophen, while the IC_(50) were determined. Inhibition kinetic analyses and docking simulations were used to investigate the inhibition modes and mechanism of wogonin(the most potent CYP1 A inhibitor in this herb), while the inhibition constants(K_i) of wogonin against both CYP1 A1 and CYP1 A2 were determined. Among all tested flavonoids, wogonin, 7-methoxyflavanone and oroxylin A displayed a strong inhibitory effect on CYP1 A(IC_(50)100 μmol·L~(-1)). Further investigations demonstrated that wogonin had a weak inhibitory effect on other human CYP enzymes, suggesting that it could be used as a lead compound for the development of specific inhibitors of CYP1 A. Furthermore, the inhibition kinetic analyses clearly demonstrated that wogonin could strongly inhibit phenacetin O-deethylation in both CYP1 A1 and CYP1 A2 in a competitive manner, with K_i values at 0.118 and 0.262 μmol·L~(-1), respectively. Molecular docking demonstrated that wogonin could strongly interact with CYP1 A1 and CYP1 A2 via hydrophobic and π-π interactions, as well as Ser120 and Ser116 in CYP1 A1 via hydrogen-bonding. In conclusion, this study found that some flavonoids in Scutellariae Radix displayed a strong inhibitory effect on CYP1 A, while wogonin is the most potent CYP1 A inhibitor with a relatively high selectivity towards CYP1 A over other human CYPs.

Particulate Matter-Induced Aryl Hydrocarbon Receptor Regulates Autophagy in Keratinocytes

Particulate matter (PM), which refers to the mixture of particles present in the air, can have harmful effects. Damage to cells by PM, including disruption of organelles and proteins, can trigger autophagy, and the relationship between autophagy and PM has been well studied. However, the cellular regulators of PM-induced autophagy have not been well characterized, especially in keratinocytes. The Aryl Hydrocarbon Receptor (AhR) is expressed in the epidermis and is activated by PM. In this study, we investigated the role of the AhR in PM-induced autophagy in HaCaT cells. Our results showed that PM led to AhR activation in keratinocytes. Activation of the AhR-target gene CYP1A1 by PM was reduced by co-treatment with α-naphthoflavone (α-NF), an AhR inhibitor. We also evaluated activation of the autophagy pathway in PM-treated keratinocytes. In HaCaT cells, treatment with PM treatment led to the induction of microtubules-associated proteins light chain 3 (LC3) and p62/SQSTM1, which are essential components of the autophagy pathway. To study the role of the AhR in mediating PM-induced autophagy, we treated cells with α-NF or used an siRNA against AhR. Expression of LC3-ІІ induced by PM was decreased in a dose dependent manner by α-NF. Furthermore, knockdown of AhR with siAhR diminished PM-induced expression of LC3-ІІ and p62. Together, these results suggest that inhibition of the AhR decreases PM-induced autophagy. We confirmed these results using the autophagy-inhibitors BAF and 3-MA. Taken together, our results indicate that exposure to PM induces autophagy via the AhR in HaCaT keratinocytes.

Computer programme to assess mandibular cortex morphology in cases of medication-related osteonecrosis of the jaw with osteoporosis or bone metastases

PURPOSE: The purpose of this study was to evaluate the morphology of the mandibular cortex in cases of medication-related osteonecrosis of the jaw (MRONJ) in patients with osteoporosis or bone metastases using a computer programme.MATERIALS AND METHODS: Fifty-four patients with MRONJ (35 with osteoporosis and 19 with bone metastases) were examined using panoramic radiography. The morphology of the mandibular cortex was evaluated using a computer programme that scanned the mandibular inferior cortex and automatically assessed the mandibular cortical index (MCI) according to the thickness and roughness of the mandibular cortex, as follows: normal (class 1), mildly to moderately eroded (class 2), or severely eroded (class 3). The MCI classifications of MRONJ patients with osteoporosis or bone metastases were evaluated with the Pearson chi-square test. In these analyses, a 5% significance level was used.RESULTS: The MCI of MRONJ patients with osteoporosis (class 1: 6, class 2: 15, class 3: 14) tended to be higher than that of patients with bone metastases (class 1: 14, class 2: 5, class 3: 0) (P=0.000).CONCLUSION: The use of a computer programme to assess mandibular cortex morphology may be an effective technique for the objective and quantitative evaluation of the MCI in MRONJ patients with osteoporosis or bone metastases.

Effects of Dendrobium huoshanense on expressions and activities of hepatic microsomal cytochrome P450s in mice / 中国中药杂志

This study was carried out to investigate the effect of oral administration of Dendrobium huoshanense on the expressions and activities of hepatic microsomal cytochrome P450s in mice, and to provide a reference for the evaluation of drug-drug interactions between D. huoshanense and clinical drugs. The C57BL/6 mice were randomly divided into blank control group, D. huoshanense low dose group (crude drug 1.25 g·kg⁻¹), D. huoshanense high dose group (crude drug 7.5 g·kg⁻¹), and phenobarbital positive control group (0.08 g·kg⁻¹). Each group was intragastrically administered with drugs for 2 weeks. The mice were sacrificed and their liver microsomes were prepared. The expressions of major subtypes of P450 enzyme were determined by Western blot and the probe drugs were used to detect the enzyme activities of P450 subtypes with protein expression changes. Western blot analysis showed that the protein expressions of CYP1A1, CYP1A2 and CYP2B in liver tissues were up-regulated in D. huoshanense-treated group. In vitro enzyme activity tests showed that there were no significant difference in metabolism of 7-ethoxyresorufin (a probe drug for CYP1A1) and bupropion (a probe drug for CYP2B) between D. huoshanense group and control group. The metabolism of phenacetin (a probe drug for CYP1A2) showed a statistical difference in rate Vmax, and it was significantly increased by approximately 20% in D. huoshanense group as compared with the blank control group, and the clearance CLint in treated group was also increased by about 32%. Therefore, oral administration of D. huoshanense had no effects on the activities of most hepatic P450 enzymes in mice, with no drug-drug interaction related to the P450 enzyme system in most clinical drugs theoretically. However, oral administration of D. huoshanense may accelerate the metabolism of CYP1A2-catalyzed drugs, which needs to be considered in clinical practice.

A Case of Posterior Semicircular Canal Dehiscence Caused by High Jugular Bulb / 대한이비인후과학회지

Posterior semicircular canal dehiscence represents a third-window lesion manifesting as hearing loss with vestibular dysfunction. Computed tomography findings of a dehiscent posterior canal can be verified with increased vestibular evoked myogenic potential responses as in other third-window lesions. The jugular bulb is the bulbiform connection between the sigmoid sinus and the internal jugular vein at the skull base. High jugular bulb can erode into inner ear structures. According to the literature review, there has been no case report about posterior semicircular canal dehiscence caused by high jugular bulb in Asia. Therefore, the authors report a case with a review of literature.

APEX1 Polymorphism and Mercaptopurine-Related Early Onset Neutropenia in Pediatric Acute Lymphoblastic Leukemia / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Mercaptopurine (MP) is one of the main chemotherapeutics for acute lymphoblastic leukemia (ALL). To improve treatment outcomes, constant MP dose titration is essential to maintain steady drug exposure, while minimizing myelosuppression. We performed two-stage analyses to identify genetic determinants of MP-related neutropenia in Korean pediatric ALL patients. MATERIALS AND METHODS: Targeted sequencing of 40 patients who exhibited definite MP intolerance was conducted using a novel panel of 211 pharmacogenetic-related genes, and subsequent analysis was performed with 185 patients. RESULTS: Using bioinformatics tools and genetic data, four functionally interesting variants were selected (ABCC4, APEX1, CYP1A1, and CYP4F2). Including four variants, 23 variants in 12 genes potentially linked to MP adverse reactions were selected as final candidates for subsequent analysis in 185 patients. Ultimately, a variant allele in APEX1 rs2307486was found to be strongly associated with MP-induced neutropenia that occurred within 28 days of initiating MP (odds ratio, 3.44; p=0.02). Moreover, the cumulative incidence of MP-related neutropenia was significantly higher in patients with APEX1 rs2307486 variants, as GG genotypes were associated with the highest cumulative incidence (p < 0.01). NUDT15 rs116855232 variants were strongly associated with a higher cumulative incidence of neutropenia (p < 0.01), and a lower median dose of tolerated MP throughout maintenance treatment (p < 0.01). CONCLUSION: We have identified that APEX1 rs2307486 variants conferred an increased risk of MP-related early onset neutropenia. APEX1 and NUDT15 both contribute to cell protection from DNA damage or misincorporation, so alleles that impair the function of either gene may affect MP sensitivities, thereby inducing MP-related neutropenia.

CYP1A1, CYP1B1, GSTM1 and GSTT1 genetic variants and breast cancer risk in Mexican women / Variantes genéticas de CYP1A1, CYP1B1, GSTM1 y GSTT1, y riesgo de cáncer mamario en mujeres mexicanas

Abstract: Objective: To evaluate if variants in the genes CYP1A1 (T3801C and A4889G), CYP1B1 (G119T), GSTM1 (indel) and GSTT1 (indel) are associated with breast cancer (BC) among Mexican women. Materials and methods: 952 incident cases with histologically confirmed BC were matched by age (± 5 years) and zone of residence with 998 healthy population controls. Genetic variants in genes CYP1A1, CYP1B1, GSTM1 and GSTT1were genotyped by allelic discrimination and multiplex PCR. In a subsample of women, 105 markers for ancestry were determined. Results: An increased BC risk, independent of other BC risk factors, was observed among carriers of CYP1B1 G119T genotype (T/T vs. G/G: OR=1.9; 95%CI 1.4-2.5). Conclusion: Our results support the existence of genetic susceptibility for BC conferred by CYP1B1 G119T variant among Mexican women.

Resumen: Objetivo: Evaluar si las variantes en los genes CYP1A1 (T3801C y A4889G), CYP1B1 (G119T), GSTM1 (indel) yGSTT1 (indel), se asocian con el cáncer de mama (CM) en mujeres mexicanas. Material y métodos: Se parearon por edad (± 5 años) y zona de residencia 952 casos incidentes de CM histológicamente confirmado con 998 controles sanos poblacionales. Se genotipificaron variantes en los genes CYP1A1, CYP1B1, GSTM1 y GSTT1 por discriminación alélica y PCR multiplex. En una submuestra de mujeres, se determinaron 105 marcadores de ancestría. Resultados: Se observó un aumento del riesgo de CM, independiente de otros factores de riesgo, entre las portadoras del genotipo CYP1B1 G119T (T/T vs. G/G: RM=1.9; 95%CI 1.4-2.5). Conclusiones: Nuestros resultados soportan la existencia de susceptibilidad genética para CM conferida por la variante CYP1B1 G119T en mujeres mexicanas.

Genetic genes associated with oligospermia, asthenospermia and teratospermia: Advances in studies / 中华男科学杂志

Approximately 2,300 genes are found to be associated with spermiogenesis and their expressions play important roles in the regulation of spermiogenesis. In recent years, more and more attention has been focused on the studies of the genes associated with oligospermia, asthenospermia and teratospermia and their molecular mechanisms. Some genes, such as GSTM1, DNMT3L, and CYP1A1, have been shown to be potentially associated with oligospermia; some, such as CATSPER1, CRISP2, SEPT4, TCTE3, TEKT4, and DNAH1, with asthenospermia; and still others, such as DPY19L2 and AURKC, with teratospermia. These findings have provided a molecular basis for the studies of the pathogenesis of oligospermia, asthenospermia and teratospermia, as well as a new approach to the exploration of new diagnostic and therapeutic techniques.

The Effect of Digestive Medicine on Enamel Erosion / 치위생과학회지

Consumption of liquid digestive medicine has continually grown in recent years. This present study was designed to evaluate the capability of liquid digestive medicine to erode dental enamel, relating the pH and titratable acidity of liquid digestive medicine. Three commercially available liquid digestive medicines were chosen these were Gashwalmyeungsu, Saengrokchun and Wicheongsu. The liquid digestive medicines were evaluated in respect to pH, titratable acidity and concentrations of calcium and phosphate, respectively. This measure was carried out three times for each digestive medicine and was recorded the data as mean (standard deviation). Bovine enamel specimens measured microhardness at base line and then were randomly assigned to 4 groups of 10 each. The specimens were immersed into each liquid digestive medicine for 1, 3, 5, 10, 15, and 30 minutes and then evaluated each time by VHN. All digestive medicines had a pH of less than 3.7. Wicheongsu had the lowest pH 2.93 and Gashwalmyeungsu had highest pH 3.63. In pH 5.5, titratable acidity of Wicheongsu was 1.27 ml. Gashwalmyeungsu was 0.63 ml. Saengrokchun was 0.60 ml. All liquid digestive medicines showed low concentration of calcium and phosphate. The microhardness of specimens after immersion into liquid digestive medicines was continuously reduced in all digestive medicines. After 30-minute treatment in liquid digestive medicines, Wicheongsu containing low pH and high tiratable acidity was shown to be lowest microhardness value (207.80µ15.52). The three liquid digestive medicines caused surface softening of enamel erosion. We conclude that drinks, commonly consumed by functional dyspepsia patient can cause erosion of enamel.

Solitary Osteochondroma Presenting as a Dumbbell Tumor Compressing the Cervical Spinal Cord

We report a case of a solitary osteochondroma as a dumbbell tumor compressing the spinal cord and its surgical strategy. The patient is a 16-year-old female with longstanding posterior neck pain and left arm abduction weakness. She was examined by plain X-ray, three-dimensional-computed tomography, magnetic resonance imaging, and vertebral angiography. The analyses indicated a calcified extradural mass compressing the cord in the C3–4 portion extending into the neural and vertebral foramen with eroded vertebral body. The tumor was successfully excised using a modified combined anterior and posterior approach. Histopathologic study of the resected material confirmed the diagnosis. The postoperative assessment was followed by clinical and radiologically therapy for 5 years after surgery. Osteochondroma arises from enchondral bone but it rarely involves the spine, especially not as s dumbbell type. In this patient, the tumor may have arisen from the neural arch and extended into the extradural and extraforaminal space over a long period. We successfully removed the dumbbell tumor with a combined anterior oblique and posterior approach. However, further observation is essential because of the possibility of recurrence and sarcomatous change.

Systemic Lupus Erythematosus Presenting as Stevens-Johnson Syndrome: A Case Report / 대한피부과학회지

Acute cutaneous lupus erythematosus (ACLE) on the face is a usual pattern of presentation. However, it can rarely present with a generalized distribution. A hyperacute form of ACLE can mimic Stevens-Johnson syndrome (SJS) and toxic epidermal necrosis (TEN). A 33-year-old man presented with erythematous eroded papules and patches on his head, neck, and upper chest over 2 months. Moreover, he showed hemorrhagic crusted erosions on his lips, and buccal and nasal mucosa, in addition to conjunctival injection. A skin biopsy from his cheek showed a mild degree of vacuolar alteration, thickening of the basement membrane, perivascular and periadnexal lymphohistiocytic infiltration, and stromal mucin deposition. Direct immunofluorescence (DIF) demonstrated IgG and IgM deposits along the basement membrane zone. Laboratory investigations demonstrated pancytopenia, positive antinuclear antibody (ANA), anti-double stranded DNA (anti-dsDNA), and anti-Ro antibodies. The patient was diagnosed with systemic lupus erythematosus (SLE) based on clinical, histological, and laboratory markers of autoimmune disease. We report a rare case of SLE presenting as SJS.

Re-Banding vs Sleeve Gastrectomy: Technical Reports and Treatment Outcomes of Two Procedures after Removal of Eroded Adjustable Gastric Band

PURPOSE: The aim of the study is to present surgical techniques and treatment outcomes of re-banding and sleeve gastrectomy after removal of eroded adjustable gastric band. MATERIALS AND METHODS: A retrospective database analysis was performed to study re-banding or LSG as revisional surgery for band erosion. Technical advancement we adopted included adhesiolysis of liver edge and cardia, retrogastric tunneling, and stapling away from fibrotic cardia. Main outcome measures were success of therapeutic strategies, morbidity, and body mass index (BMI), percentage excess weight loss [%EWL] before and after revision. RESULTS: From 2013 to 2017, a total of 11 patients underwent revisional surgery. Male to female was ratio was 1:10. Six patients underwent revisional sleeve gastrectomy, and five patients underwent re-banding. One patient in sleeve gastrectomy group was diagnosed to have minor leak on CT scan, and recovered by conservative management. The median BMI of the six patients who underwent sleeve gastrectomy was 29.5 kg/m² (27.9 kg/m²–40.8 kg/m²), their median follow-up was 24.8 months (6.5–54.7 months), and their BMI and %EWL at last follow-up was 24.4 kg/m² (22.5 kg/m²–34.6 kg/m²) and 78.4% (19.2%–110.2%) respectively. The median BMI of the five patients who underwent rebanding was 27.3 kg/m² (26.1 kg/m²–41.4 kg/m²), their median follow-up was 16.5 months (4.5–36.4 months), and their BMI and %EWL at last follow-up was 23.5 kg/m² (22.0 kg/m²–30.1 kg/m²) and 83.9% (36.4–123.3%) respectively. CONCLUSION: With advanced surgical techniques we adopted, both re-banding and sleeve gastrectomy are safe and effective as a revisional procedure after removal of eroded gastric band.

Subfrontal Schwannoma Extended Broadly to Nasal Cavity Treated by Gamma Knife Radiosurgery Following Surgical Excision: A Case Report

Subfrontal schwannomas are rarely reported. They are usually found only in the subfrontal area, but some extend to the nasal cavity. In these cases, prevention of postoperative cerebrospinal fluid (CSF) leakage through thinned or eroded anterior skull base is important. A 51-year-old female with anosmia and mild nausea was diagnosed as subfrontal extraaxial mass with nasal cavity extension. This mass was initially thought to be an olfactory groove meningioma. We performed a bifrontal craniotomy for surgical excision. We did not totally remove the tumor, as we wanted to prevent a skull base defect. The histopathological diagnosis was a schwannoma. There was no postoperative complication such as CSF leakage. The residual tumor was treated with gamma knife radiosurgery. The nasal cavity mass has not grown as of five years after radiosurgery.

Parotid mandibular bone defect: A case report emphasizing imaging features in plain radiographs and magnetic resonance imaging

Mandibular bone depression, also known as Stafne bone cavity, is defined as a bone depression filled mainly with salivary gland tissue. Parotid gland bone defects are infrequently observed. We report the case of a 52-year-old male patient who underwent radiographic examinations due to temporomandibular joint dysfunction, and a radiolucent area was detected in the mandibular ramus, with a provisional diagnosis of traumatic bone cyst or parotid mandibular bone defect. The patient was then referred for magnetic resonance imaging, which demonstrated a hyperintense area eroding the mandibular ramus, which corresponded to glandular tissue. Although the defect was a benign lesion, radiolucencies in the mandibular ramus lead to concerns among professionals, because their radiographic features can resemble various intrabony neoplastic lesions, such as giant cell tumors or benign tumors of the parotid gland.

Ginsenoside Rb1 Inhibits Doxorubicin-Triggered H9C2 Cell Apoptosis via Aryl Hydrocarbon Receptor

Doxorubicin (DOX) is a highly effective chemotherapeutic agent; however, the dose-dependent cardiotoxicity associated with DOX significantly limits its clinical application. In the present study, we investigated whether Rb1 could prevent DOX-induced apoptosis in H9C2 cells via aryl hydrocarbon receptor (AhR). H9C2 cells were treated with various concentrations (−μM) of Rb1. AhR, CYP1A protein and mRNA expression were quantified with Western blot and real-time PCR analyses. We also evaluated the expression levels of caspase-3 to assess the anti-apoptotic effects of Rb1. Our results showed that Rb1 attenuated DOX-induced cardiomyocytes injury and apoptosis and reduced caspase-3 and caspase-8, but not caspase-9 activity in DOX-treated H9C2 cells. Meanwhile, pre-treatment with Rb1 decreased the expression of caspase-3 and PARP in the protein levels, with no effects on cytochrome c, Bax, and Bcl-2 in DOX-stimulated cells. Rb1 markedly decreased the CYP1A1 and CYP1A2 expression induced by DOX. Furthermore, transfection with AhR siRNA or pre-treatment with AhR antagonist CH-223191 significantly inhibited the ability of Rb1 to decrease the induction of CYP1A, as well as caspase-3 protein levels following stimulation with DOX. In conclusion, these findings indicate that AhR plays an important role in the protection of Ginsenoside Rb1 against DOX-triggered apoptosis of H9C2 cells.