2,4,6-Triphenyl-1-hexene, an Anti-Melanogenic Compound from Marine-Derived Bacillus sp. APmarine135.

Although melanin protects against ultraviolet radiation, its overproduction causes freckles and senile lentigines. Recently, various biological effects of metabolites derived from marine microorganisms have been highlighted due to their potential for biological and pharmacological applications. In this study, we discovered the anti-melanogenic effect of Bacillus sp. APmarine135 and verified the skin-whitening effect. Fractions of APmarine135 showed the melanin synthesis inhibition effect in B16 melanoma cells, and 2,4,6-triphenyl-1-hexene was identified as an active compound. The melanogenic capacity of 2,4,6-triphenyl-1-hexene (1) was investigated by assessing the intracellular melanin content in B16 cells. Treatment with 5 ppm of 2,4,6-triphenyl-1-hexene (1) for 72 h suppressed the α-melanocyte-stimulating hormone (α-MSH)-induced intracellular melanin increase to the same level as in the untreated control group. Additionally, 2,4,6-triphenyl-1-hexene (1) treatment suppressed the activity of tyrosinase, the rate-limiting enzyme for melanogenesis. Moreover, 2,4,6-triphenyl-1-hexene (1) treatment downregulated tyrosinase, Tyrp-1, and Tyrp-2 expression by inhibiting the microphthalmia-associated transcription factor (MITF). Furthermore, 2,4,6-triphenyl-1-hexene (1) treatment decreased the melanin content in the three-dimensional (3D) human-pigmented epidermis model MelanoDerm and exerted skin-whitening effects. Mechanistically, 2,4,6-triphenyl-1-hexene (1) exerted anti-melanogenic effects by suppressing tyrosinase, Tyrp-1, and Tyrp-2 expression and activities via inhibition of the MITF. Collectively, these findings suggest that 2,4,6-triphenyl-1-hexene (1) is a promising anti-melanogenic agent in the cosmetic industry.

Structural insight into crystal structure of helicase domain of DDX53.

DEAD box helicase proteins are a family of RNA helicases that participate in various RNA metabolisms such as RNA unwinding, RNA processing, and RNPase activities. A particular DEAD box protein, the DDX53 protein, is primarily expressed in cancer cells and plays a crucial role in tumorigenesis. Numerous studies have revealed that DDX53 interacts with various microRNA and Histone deacetylases. However, its molecular structure and the detailed binding interaction between DDX53 and microRNA or HDAC is still unclear. In this study, we used X-ray crystallography to investigate the 3D structure of the hlicase C-terminal domain of DDX53, and successfully determined its crystal structure at a resolution of 1.97 Å. Subsequently, a functional analysis of RNA was conducted by examining the binding properties thereof with DDX53 by transmission electron microscopy and computing-based molecular docking simulation. The defined 3D model of DDX53 not only provides a structural basis for the fundamental understanding of DDX53 but is also expected to contribute to the field of anti-cancer drug discovery such as structure-based drug discovery and computer-aided drug design.

Folate deficiency is associated with increased radiographic severity of osteoarthritis in knee joints but not in hand joints.

OBJECTIVES: No previous studies have explored the effect of folate deficiency on the severity of osteoarthritis (OA). Therefore, we investigated the relationship between folate level and features on knee and hand radiographs in a large, population-based OA cohort. METHODS: Among 9,260 subjects enrolled in the Dong-gu study, 2,489 who had knee and hand joint radiographs were included. Of these, subjects with a history of amputation or total knee replacement were excluded. Serum folate levels were measured using blood samples collected at the time of enrolment and stored. A semi-quantitative system was used to grade the severity of hand and knee x-ray changes. Linear regression was performed to assess relationships between serum folate levels and knee and hand radiographic scores after adjusting for age, sex, body mass index, smoking, alcohol consumption, education, physical activity, occupation, vitamin D, and ferritin. RESULTS: A total of 2,322 subjects were recruited. After adjusting for confounders, participants with folate deficiency (<4 ng/mL) had higher total (p<0.001), osteophyte (p<0.001), joint space narrowing (p=0.002), tibial attrition (p<0.001), and sclerosis (p=0.005) scores for knee joint radiographs compared to participants with a normal folate level. After adjusting for confounders, the radiographic scores for hand joints did not differ between the groups. CONCLUSIONS: Folate deficiency is associated with increased radiographic severity of OA in knee joints, but not in hand joints. Further studies are needed to explore the differential effects of folate on the severity of knee and hand OA.

Proteomics-based diagnostic peptide discovery for severe fever with thrombocytopenia syndrome virus in patients.

BACKGROUND: Severe fever with thrombocytopenia syndrome (SFTS) virus is an emerging infectious virus which causes severe hemorrhage, thrombocytopenia, and leukopenia, with a high fatality rate. Since there is no approved therapeutics or vaccines for SFTS, early diagnosis is essential to manage this infectious disease. METHODS: Here, we tried to detect SFTS virus in serum samples from SFTS patients by proteomic analysis. Firstly, in order to obtain the reference MS/MS spectral data of SFTS virus, medium from infected Vero cell culture was used for shotgun proteomic analysis. Then, tryptic peptides in sera from SFTS patients were confirmed by comparative analysis with the reference MS/MS spectral data of SFTS virus. RESULTS: Proteomic analysis of culture medium successfully discovered tryptic peptides from all the five antigen proteins of SFTS virus. The comparative spectral analysis of sera of SFTS patients revealed that the N-terminal tryptic peptide of the nucleocapsid (N) protein is the major epitope of SFTS virus detected in the patient samples. The prevalence of the peptides was strongly correlated with the viral load in the clinical samples. CONCLUSIONS: Proteomic analysis of SFTS patient samples revealed that nucleocapsid (N) protein is the major antigen proteins in sera of SFTS patients and N-terminal tryptic peptide of the N protein might be a useful proteomic target for direct detection of SFTS virus. These findings suggest that proteomic analysis could be an alternative tool for detection of pathogens in clinical samples and diagnosis of infectious diseases.

Association between ALDH2 polymorphism and esophageal cancer risk in South Koreans: a case-control study.

BACKGROUND: Alcohol consumption is a major risk factor for esophageal cancer; however, a high incidence of esophageal cancer is observed particularly among Eastern Asians, although they consume relatively less alcohol, presumably due to the high frequency of aldehyde dehydrogenase 2 (ALDH2) rs671 polymorphisms. Nevertheless, the association between ALDH2 polymorphisms and esophageal cancer remains under debate. In the present study, we evaluated the association between ALDH2 rs671 polymorphisms and the risk of esophageal cancer in the South Korean population. METHODS: This study included 783 hospital based-cases and 8732 population-based controls. Information on smoking history and alcohol consumption was obtained from the medical records or interview questionnaires. Age-adjusted logistic regression analysis was performed to assess the association between ALDH2 rs671 polymorphisms and esophageal cancer. RESULTS: Odds ratios (ORs) for esophageal cancer in men with GA and AA genotypes were 2.75 (95% confidence interval [CI]: 2.34-3.23) and 0.08 (95% CI: 0.00-0.35), respectively; whereas, in women, these ratios were 2.99 (95% CI: 1.43-6.34) and 6.18 (95% CI: 1.40-19.62), respectively, taking subjects with the ALDH2 GG genotype as a reference. In men, the association between ALDH2 polymorphisms and esophageal cancer was modified by alcohol consumption. CONCLUSION: In Eastern Asians, ALDH2 rs671 polymorphisms are associated with esophageal cancer, which may be linked to acetaldehyde accumulation.

Association between Alcohol Consumption and Serum Cortisol Levels: a Mendelian Randomization Study.

BACKGROUND: Several studies have reported conflicting results regarding the relationship between alcohol consumption and cortisol levels. However, the causality between alcohol consumption and cortisol levels has not been evaluated. METHODS: This study examined 8,922 participants from the Dong-gu Study. The aldehyde dehydrogenase 2 (ALDH2) rs671 polymorphism was used as an instrumental variable for alcohol consumption. The association between the genetically predicted alcohol consumption and cortisol level was evaluated with Mendelian randomization (MR) using two-stage least squares regression. RESULTS: Alcohol consumption was positively associated with the serum cortisol level in both sexes in the observational analysis. In the MR analysis, the genetically predicted alcohol consumption was positively related to the cortisol level in men, with cortisol levels increasing by 0.18 µg/dL per drink per day. However, there was no relationship in women in the MR analysis. CONCLUSION: The predicted alcohol consumption according to the ALDH2 rs671 polymorphism was positively related to the cortisol levels, suggesting a causal relationship between alcohol consumption and cortisol levels.

Association between ALDH2 Polymorphism and Gastric Cancer Risk in a Korean Population.

The association between alcohol and gastric cancer is stronger in East Asians than in other ethnic groups, presumably due to an aldehyde dehydrogenase 2 (ALDH2) polymorphism. Therefore, we investigated the relationship between the ALDH2 rs671 polymorphism and gastric cancer in a Korean population. This case-control study included 3,245 hospital patients newly diagnosed with gastric cancer and 8,732 population controls. The ALDH2 rs671 genotype was classified as inactive ALDH2 (GG) or active ALDH2 (GA/AA). The risk of gastric cancer was higher in men with the inactive ALDH2 than in those with active ALDH2 (odds ratio [OR], 1.25; 95% confidence interval [CI], 1.09-1.39), whereas no significant association was found between ALDH2 genotype and gastric cancer in women (OR, 1.00; 95% CI, 0.99-1.02). In men, the association between ALDH2 genotype and gastric cancer was stronger in current drinkers. Our findings support the previously reported association between inactive ALDH2 and high risk of gastric cancer.

Effect Modification of Acetaldehyde Dehydrogenase 2 rs671 Polymorphism on the Association between Alcohol Intake and Blood Pressure: the Dong-gu Study.

BACKGROUND: Elevated blood pressure is a major preventable cause of cardiovascular diseases. Alcohol consumption is a well-known risk factor of elevated blood pressure. The aldehyde dehydrogenase 2 (ALDH2) polymorphism is common in Eastern Asians, and inactive ALDH2 genotypes are associated with both avoiding alcohol consumption and aldehyde accumulation. Therefore, this study assessed the associations between alcohol consumption and hypertension and blood pressure according to the ALDH2 genotypes. METHODS: This study consists of 8,526 participants in the Dong-gu Study. Multivariate logistic regression was used to calculate the odds ratio (OR) according to alcohol consumption after stratifying by gender and ALDH2 genotypes. Multivariate linear regression was performed to estimate the systolic blood pressure (SBP) and diastolic blood pressure (DBP) according to the amount of alcohol consumed. RESULTS: In men, alcohol consumption was positively associated with both SBP and DBP in active ALDH2 carriers, but not in inactive ALDH2 carriers. In active ALDH2 carriers, compared to non-drinkers, the OR of hypertension was 1.16 (95% confidence interval [CI], 0.91-1.49) for < 1 drink/day, and 1.44 (95% CI, 1.15-1.80) for ≥ 1 drink/day in men. With each 1 drink/day increase, SBP and DBP increased by 3 and 1 mmHg in men, respectively. There was no significant association between ALDH2 genotypes and hypertension and blood pressure in women. CONCLUSION: ALDH2 genotype modified the association between alcohol consumption and blood pressure in men. There was a positive relationship between alcohol consumption and blood pressure in active ALDH2 carriers, but no significant relationship in inactive ALDH2 carriers.

O-GlcNAcylation of light chain serine 12 mediates rituximab production doubled by thiamet G.

O-Glycosylation occurs in recombinant proteins produced by CHO cells, but this phenomenon has not been studied extensively. Here, we report that rituximab is an O-linked N-acetyl-glucosaminylated (O-GlcNAcylated) protein and the production of rituximab is increased by thiamet G, an inhibitor of O-GlcNAcase. The production of rituximab doubled with OGA inhibition and decreased with O-GlcNAc transferase inhibition. O-GlcNAc-specific antibody and metabolic labelling with azidO-GlcNAc confirmed the increased O-GlcNAcylation with thiamet G. Protein mass analysis revealed that serine 7, 12, and 14 of the rituximab light chain were O-GlcNAcylated. S12A mutation of the light chain decreased rituximab stability and failed to increase the production with thiamet G without any significant changes of mRNA level. Cytotoxicity and thermal stability assays confirmed that there were no differences in the biological and physical properties of rituximab produced by thiamet G treatment. Therefore, thiamet G treatment improves the production of rituximab without significantly altering its function.

Low binding affinity and reduced complement-dependent cell death efficacy of ofatumumab produced using a plant system (Nicotiana benthamiana L.).

The plant protein production system is a platform that can not only reduce production costs but also produce monoclonal antibodies that do not have the risk of residual proteins from the host. However, due to the difference between post-translational processes in plants and animals, there may be a modification in the Fab region of the monoclonal antibody produced in the plant; thus, it is necessary to compare the antigen affinity of this antibody with that of the prototype. In this study, ofatumumab, a fully human anti-CD20 IgG1κ monoclonal antibody used for its non-cross resistance to rituximab, was expressed in Nicotiana benthamiana, and its affinities and efficacies were compared with those of native ofatumumab produced from CHO cells. Two forms of plant ofatumumab (with or without HDEL-tag) were generated and their production yields were compared. The HDEL-tagged ofatumumab was more expressed in plants than the form without HDEL-tag. The specificity of the target recognition of plant-derived ofatumumab was confirmed by mCherry-CD20-expressing HEK cells via immuno-staining, and the capping of CD20 after ofatumumab binding was also confirmed using Ramos B cells. In the functional equivalence tests, the binding affinities and complement-dependent cell cytotoxicity efficacy of plant-ofatumumab-HDEL and plant-ofatumumab without HDEL were significantly reduced compared to those of CHO-derived ofatumumab. Therefore, we suggest that although ofatumumab is not a good candidate as a template for plant-derived monoclonal antibodies because of its decreased affinity when produced in plants, it is an interesting target to study the differences between post-translational modifications in mammals and plants.

The Association between the Apolipoprotein E Gene Polymorphism and All-cause Mortality in the Korean Population.

BACKGROUND: Apolipoprotein E (APOE) gene polymorphism is associated with neurodegenerative and cardiovascular diseases. Although the effects of the gene differ by ethnic group, few studies have examined Asians. Therefore, the association between APOE polymorphism and mortality in Koreans was evaluated in this study. METHODS: This study population included participants from the Dong-gu and Namwon Studies. APOE genotypes were categorized as E2 (E2/E2 and E2/E3), E3 (E3/E3), and E4 (E3/E4 and E4/E4). Multivariate Cox proportional hazard models were constructed using the E3 allele as a reference. RESULTS: In the model adjusting for study site, age, gender, and lifestyle, the hazard ratio (HR) of mortality for those with the E4 allele was 1.08 (95% confidence interval [CI], 0.97-1.20), while that for those with the E2 allele was 0.84 (95% CI, 0.74-0.96). After adjusting for blood lipids to evaluate their mediating effects, the HRs of mortality for those with E4 and E2 alleles were 1.08 (95% CI, 0.97-1.20) and 0.80 (95% CI, 0.70-0.92), respectively. These associations were more evident in younger groups, with HRs of 0.70 (95% CI, 0.52-0.92) for the E2 allele and 1.25 (95% CI, 1.03-1.53) for the E4 allele. CONCLUSION: In two large population-based cohort studies, the E2 allele was associated with a lower risk of mortality compared with the E3 allele, whereas the E4 genotype was not associated with mortality in Koreans.

Antibiotic treatment modulates protein components of cytotoxic outer membrane vesicles of multidrug-resistant clinical strain, Acinetobacter baumannii DU202.

BACKGROUND: Outer membrane vesicles (OMVs) of Acinetobacter baumannii are cytotoxic and elicit a potent innate immune response. OMVs were first identified in A. baumannii DU202, an extensively drug-resistant clinical strain. Herein, we investigated protein components of A. baumannii DU202 OMVs following antibiotic treatment by proteogenomic analysis. METHODS: Purified OMVs from A. baumannii DU202 grown in different antibiotic culture conditions were screened for pathogenic and immunogenic effects, and subjected to quantitative proteomic analysis by one-dimensional electrophoresis and liquid chromatography combined with tandem mass spectrometry (1DE-LC-MS/MS). Protein components modulated by imipenem were identified and discussed. RESULTS: OMV secretion was increased > twofold following imipenem treatment, and cytotoxicity toward A549 human lung carcinoma cells was elevated. A total of 277 proteins were identified as components of OMVs by imipenem treatment, among which ß-lactamase OXA-23, various proteases, outer membrane proteins, ß-barrel assembly machine proteins, peptidyl-prolyl cis-trans isomerases and inherent prophage head subunit proteins were significantly upregulated. CONCLUSION: In vitro stress such as antibiotic treatment can modulate proteome components in A. baumannii OMVs and thereby influence pathogenicity.

Ligand-Mediated Folding of the OmpA Periplasmic Domain from Acinetobacter baumannii.

The periplasmic domain of OmpA from Acinetobacter baumannii (AbOmpA-PD) binds to diaminopimelate and anchors the outer membrane to the peptidoglycan layer in the cell wall. Although the crystal structure of AbOmpA-PD with its ligands has been reported, the mechanism of ligand-mediated folding of AbOmpA remains elusive. Here, we report that in vitro refolded apo-AbOmpA-PD in the absence of ligand exists as a mixture of two partially folded forms in solution: mostly unfolded (apo-state I) and hololike (apo-state II) states. Binding of the diaminopimelate or glycine ligand induced complete folding of AbOmpA-PD. The apo-state I was highly flexible and contained some secondary structural elements, whereas the apo-state II closely resembled the holo-state in terms of both structure and backbone dynamics, except for the ligand-binding region. 15N-relaxation-dispersion analyses for apo-state II revealed substantial motion on a millisecond timescale of residues in the H3 helix near the ligand-binding site, with this motion disappearing upon ligand binding. These results provide an insight into the ligand-mediated folding mechanism of AbOmpA-PD in solution.

Crystal structure analysis of 3,6-anhydro-l-galactonate cycloisomerase suggests emergence of novel substrate specificity in the enolase superfamily.

3,6-Anydro-l-galatonate cycloisomerase (ACI) catalyzes the cycloisomerization of a 3,6-anhydro-l-galactonic acid known as a novel metabolite in agarolytic bacteria. Here, we present 3-D structures of ACI from Vibrio sp. strain EJY3 (VejACI) in native and mutant forms at 2.2 Å and 2.6 Å resolutions, respectively. The enzyme belongs to the mandelate racemase subgroup of the enolase superfamily catalyzing common ß-elimination reactions by α-carbon deprotonation of substrates. The structure of VejACI revealed a notable 20s loop region in the capping domain, which can be a highly conserved structural motif in ACI homologs of agar metabolism. By comparing mutant (mVejAC/H300 N) and native VejACI structures, we identified a conformational change of Ile142 in VejACI that causes spatial expansion in the binding pocket. These observations imply that Ile142 and the 20s loop play important roles in enzymatic reactivity and substrate specificity. The structural phylogenetic analysis of the enolase superfamily including ACIs revealed sequential, structural, and functional relationships related to the emergence of novel substrate specificity.

Crystal structure analysis of a bacterial aryl acylamidase belonging to the amidase signature enzyme family.

The atomic structure of a bacterial aryl acylamidase (EC 3.5.1.13; AAA) is reported and structural features are investigated to better understand the catalytic profile of this enzyme. Structures of AAA were determined in its native form and in complex with the analgesic acetanilide, p-acetaminophenol, at 1.70 Å and 1.73 Å resolutions, respectively. The overall structural fold of AAA was identified as an α/ß fold class, exhibiting an open twisted ß-sheet core surrounded by α-helices. The asymmetric unit contains one AAA molecule and the monomeric form is functionally active. The core structure enclosing the signature sequence region, including the canonical Ser-cisSer-Lys catalytic triad, is conserved in all members of the Amidase Signature enzyme family. The structure of AAA in a complex with its ligand reveals a unique organization in the substrate-binding pocket. The binding pocket consists of two loops (loop1 and loop2) in the amidase signature sequence and one helix (α10) in the non-amidase signature sequence. We identified two residues (Tyr(136) and Thr(330)) that interact with the ligand via water molecules, and a hydrogen-bonding network that explains the catalytic affinity over various aryl acyl compounds. The optimum activity of AAA at pH > 10 suggests that the reaction mechanism employs Lys(84) as the catalytic base to polarize the Ser(187) nucleophile in the catalytic triad.

Structural basis of the heterodimerization of the MST and RASSF SARAH domains in the Hippo signalling pathway.

Despite recent progress in research on the Hippo signalling pathway, the structural information available in this area is extremely limited. Intriguingly, the homodimeric and heterodimeric interactions of mammalian sterile 20-like (MST) kinases through the so-called `SARAH' (SAV/RASSF/HPO) domains play a critical role in cellular homeostasis, dictating the fate of the cell regarding cell proliferation or apoptosis. To understand the mechanism of the heterodimerization of SARAH domains, the three-dimensional structures of an MST1-RASSF5 SARAH heterodimer and an MST2 SARAH homodimer were determined by X-ray crystallography and were analysed together with that previously determined for the MST1 SARAH homodimer. While the structure of the MST2 homodimer resembled that of the MST1 homodimer, the MST1-RASSF5 heterodimer showed distinct structural features. Firstly, the six N-terminal residues (Asp432-Lys437), which correspond to the short N-terminal 310-helix h1 kinked from the h2 helix in the MST1 homodimer, were disordered. Furthermore, the MST1 SARAH domain in the MST1-RASSF5 complex showed a longer helical structure (Ser438-Lys480) than that in the MST1 homodimer (Val441-Lys480). Moreover, extensive polar and nonpolar contacts in the MST1-RASSF5 SARAH domain were identified which strengthen the interactions in the heterodimer in comparison to the interactions in the homodimer. Denaturation experiments performed using urea also indicated that the MST-RASSF heterodimers are substantially more stable than the MST homodimers. These findings provide structural insights into the role of the MST1-RASSF5 SARAH domain in apoptosis signalling.

Evaluation of elevated urinary enolase I levels in patients with endometriosis.

OBJECTIVE: The aim of this study is to validate and investigate the clinical value of urinary enolase I in patients with endometriosis. METHODS: Urine samples of 39 patients with histologically confirmed endometriosis and 20 patients without endometriosis were collected. Western blot analysis and enzyme-linked immunosorbent assay were used to detect the increase of enolase I in patients' urine. RESULTS: Urinary enolase I expression corrected for creatinine ratio (non neuronal enolase (NNE)-Cr) was significantly greater in patients with endometriosis (p = 0.026). When the diagnostic performance of NNE-Cr was evaluated with serum CA-125 combination, the area under the curve was 0.821 (95% confidence interval 0.713-0.928) with sensitivity and specificity of 76.9% and 85.0%, respectively. CONCLUSION: Elevated urinary enolase I, in conjunction with serum CA-125, may be used as a potential biomarker for endometriosis.

Dose-response relationship between serum γ-glutamyltransferase and arterial stiffness in Korean adults: the Namwon Study.

BACKGROUND: The results of epidemiologic studies of the association between serum γ-glutamyltransferase (GGT) and brachial-ankle pulse wave velocity (baPWV) have been inconsistent. We examined the association between serum GGT and arterial stiffness in a general population of Korean adults. METHODS: The study population consisted of 6314 community-dwelling Koreans who participated in the baseline survey of the Namwon Study. We analyzed sex-specific association between serum GGT and arterial stiffness, as measured by baPWV. RESULTS: There was a significant progressive increase in age-adjusted mean baPWV across quartiles of GGT in both sexes. In fully adjusted analysis, as compared with the lowest quartile, the odds ratios (95% CI) for high baPWV (ie, sex-specific fifth quintile) were 1.51 (1.03-2.23), 1.82 (1.22-2.72), and 2.80 (1.79-4.40) among men (P-trend <0.001), and 1.11 (0.81-1.52), 1.29 (0.94-1.76), and 1.47 (1.04-2.08) among women (P-trend <0.001), for the second, third, and fourth quartiles of GGT, respectively. CONCLUSIONS: This population-based study examined the dose-response relationship between GGT and arterial stiffness as measured by baPWV in both sexes. The association between GGT and arterial stiffness was stronger among men. Additional longitudinal studies are needed to examine the relationship between GGT and arterial stiffness and clarify the mechanism underlying the association.

Postoperative levonorgestrel-releasing intrauterine system versus oral contraceptives after gonadotropin-releasing hormone agonist treatment for preventing endometrioma recurrence.

OBJECTIVE: Although the levonorgestrel-releasing intrauterine system (LNG-IUS) is effective in reducing the recurrence of endometriosis-associated pain, its efficacy in preventing endometrioma recurrence is questionable. We compared the efficacy of postoperative use of LNG-IUS with oral contraceptives (OC) for preventing endometrioma recurrence. DESIGN: A retrospective cohort study. SETTING: Medical university hospital. POPULATION: Ninety-nine women with endometriomas. METHODS: A chart review was performed of women of reproductive age who had undergone laparoscopic surgery for endometrioma followed by three cycles of gonadotropin-releasing hormone agonist (leuprolide acetate) treatment. Women were categorized into two groups: a group that had postoperative LNG-IUS placement (n = 42) and a group that received postoperative, cyclic, low-dose, monophasic, OCs (n = 57). Main outcome measures. Endometrioma recurrence was analyzed according to several clinical variables and postoperative treatment modalities. RESULTS: During the follow-up period (median 17 months), recurrent endometriomas were detected in eight women (8.1%). Patients with LNG-IUS had a recurrence rate of 4.8% (2/42), whereas women receiving OC had a recurrence rate of 10.5% (6/57). Cumulative recurrence-free survival assessment revealed that mean disease-free survival times for both groups were similar, but that for LNG-IUS was slightly longer than that for OC, with statistical significance (34.4 ± 1.0 months, 95% confidence interval 32.3­36.5, vs. 33.4 ± 1.3 months, 95% confidence interval 30.8­36.0, p = 0.045). Univariate analysis revealed a hazard ratio of 0.178 (95% confidence interval 0.029­1.075) (p = 0.060) for postoperative LNG-IUS use and endometrioma recurrence. However, for the multivariate regression analysis, only postoperative serum CA 125 levels were significantly associated with endometrioma recurrence (hazard ratio 1.012, p = 0.010). CONCLUSIONS: Postoperative LNG-IUS use seemed to be comparable to the use of cyclic OC in preventing endometrioma recurrence.

Short-term Impact of Hormone Replacement Therapy on Risk of Breast Cancer in BRCA Mutation Carriers: A Nationwide Study in South Korea.

PURPOSE: BRCA1/2 mutations are well-known risk factors for breast and ovarian cancers in women. Risk-reducing salpingo-oophorectomy (RRSO) is the standard treatment for preventing ovarian cancer with BRCA mutations. Postmenopausal syndrome (symptoms after RRSO can be alleviated by hormone replacement therapy (HRT); however, the use of HRT in carriers of BRCA mutations has been controversial because of the concern that HRT increases the risk of breast cancer. This study aimed to evaluate the effects of HRT in BRCA mutation carriers who underwent RRSO. MATERIALS AND METHODS: A total of 151 carriers, who underwent RRSO between 2013 and 2020 after the diagnosis of BRCA1 or BRCA2 mutations were selected and followed up for a median of 3.03 years. Patients were divided into two groups: those who received HRT after RRSO (n=33) and those who did not (n=118). We compared the incidence of breast cancer over time between these two groups. RESULTS: There was no significant difference in the incidence of breast cancer between women who received HRT and those who did not (p=0.229). Multivariate logistic regression analysis, adjusted for age and parity revealed no significant difference in the risk of breast cancer between these two groups (hazard ratio, 0.312; 95% confidence interval, 0.039 to 2.480; p=0.278). CONCLUSION: In this study, we found no relationship between post-RRSO HRT and breast cancer in the population with BRCA mutations. Therefore, healthcare providers may consider the alleviation of symptoms of postmenopausal syndrome through HRT in patients who underwent RRSO.