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Abstract The human microbiome contains genetic information that regulates metabolic processes in response to host health and disease. While acidic vaginal pH is maintained in normal conditions, the pH level increases in infectious vaginitis. We propose that this change in the vaginal environment triggers the biosynthesis of anti-vaginitis metabolites. Gene expression levels of Chryseobacterium gleum, a vaginal symbiotic bacterium, were found to be affected by pH changes. The distinctive difference in the metabolic profiles between two C. gleum cultures incubated under acidic and neutral pH conditions was suggested to be an anti-vaginitis molecule, which was identified as phenylacetic acid (PAA) by spectroscopic data analysis. The antimicrobial activity of PAA was evaluated in vitro, showing greater toxicity toward Gardnerella vaginalis and Candida albicans, two major vaginal pathogens, relative to commensal Lactobacillus spp. The activation of myeloperoxidase, prostaglandin E2, and nuclear factor-κB, and the expression of cyclooxygenase-2 were reduced by an intravaginal administration of PAA in the vaginitis mouse model. In addition, PAA displayed the downregulation of mast cell activation. Therefore, PAA was suggested to be a messenger molecule that mediates interactions between the human microbiome and vaginal health.

Purpose: Infertility affects 10% to 15% of couples, and male factor accounts for 50% of the cases. The relevant male genetic factors, which account for at least 15% of male infertility, include Y-chromosome microdeletions. We investigated clinical data and patterns of Y-chromosome microdeletions in Korean infertile men. Materials and Methods: A total of 919 infertile men whose sperm concentration was ≤5 million/mL in two consecutive analyses were investigated for Y-chromosome microdeletion. Among them, 130 infertile men (14.1%) demonstrated Y-chromosome microdeletions. Medical records were retrospectively reviewed. Results: In 130 men with Y-chromosome microdeletions, 90 (69.2%) had azoospermia and 40 (30.8%) had severe oligozoospermia. The most frequent microdeletions were in the azoospermia factor (AZF) c region (77/130, 59.2%), followed by the AZFb+c (30/130, 23.1%), AZFa (8/130, 6.2%), AZFb (7/130, 5.4%), AZFa+b+c (7/130, 5.4%), and AZFa+c (1/130, 0.7%) regions. In men with oligozoospermia, 37 (92.5%) had AZFc microdeletion. Chromosomal abnormalities were detected in 30 patients (23.1%). Higher follicle-stimulating hormone level (23.2±13.5 IU/L vs. 15.1±9.0 IU/L, p

Accumulating evidence indicates that microbial communities in the human body crucially affect health through the production of chemical messengers. However, the relationship between human microbiota and cancer has been underexplored. As a result of a biochemical investigation of the commensal oral microbe, Corynebacterium durum, we identified the non-enzymatic transformation of tryptamine into an anticancer compound, durumamide A (1). The structure of 1 was determined using LC-MS and NMR data analysis as bis(indolyl)glyoxylamide, which was confirmed using one-pot synthesis and X-ray crystallographic analysis, suggesting that 1 is an oxidative dimer of tryptamine. Compound 1 displayed cytotoxic activity against various cancer cell lines with IC50 values ranging from 25 to 35 μM. A drug affinity responsive target stability assay revealed that survivin is the direct target protein responsible for the anticancer effect of 1, which subsequently induces apoptosis-inducing factor (AIF)-mediated apoptosis. Inspired by the chemical structure and bioactivity of 1, a new derivative, durumamide B (2), was synthesized using another indole-based neurotransmitter, serotonin. The anticancer properties of 2 were similar to those of 1; however, it was less active. These findings reinforce the notion of human microbiota-host interplay by showing that 1 is naturally produced from the human microbial metabolite, tryptamine, which protects the host against cancer.

Purpose: We compared semen quality and sperm DNA fragmentation in cancer patients who underwent sperm banking and controls who underwent sperm cryopreservation for assisted reproductive technology (ART). Materials and Methods: A total of 132 men, 65 cancer patients and 67 controls, were prospectively enrolled and performed sperm cryopreservation for fertility preservation from May 2019 to February 2021. Sperm quality was determined by measuring semen volume, sperm concentration, sperm motility, and sperm DNA fragmentation index (DFI). Sperm quality and sperm DFI were compared in cancer patients and controls. Results: The major cancers of the 65 cancer patients were leukemia (26.2%), testicular cancer (23.1%), and lymphoma (20.0%). Sperm concentration, sperm total motility, and sperm progressive motility were significantly lower in cancer patients than in controls. Sperm DFI was significantly higher in cancer patients than in controls (24.32%±15.69% vs. 19.11%±11.63%; p=0.033). After excluding 8 cancer patients who received chemotherapy before sperm banking, sperm concentration, sperm total motility, and sperm progressive motility were significantly lower in cancer patients than in controls, but there was no significant difference in sperm DFI for cancer patients and controls (23.14%±12.79% vs. 19.11%±11.63%; p=0.069). Conclusions: Sperm quality was lower in cancer patients than in controls. There was no difference in the sperm DFI of cancer patients prior to chemotherapy and men presenting for sperm cryopreservation for ART. We recommend that all men who are planning cancer therapy should be offered sperm banking prior to gonadotoxic chemotherapy as a standard of fertility preservation.

Purpose: There have been concerns regarding potential effects of older paternal age on male reproductive function. However, currently available data on this topic are insufficient and controversy exists. We analyzed semen characteristics and reproductive hormones in young men and middle-aged men to investigate the effect of age on male reproductive function. Materials and Methods: This study examined healthy males of reproductive age who visited a single infertility center from January 2016 to July 2021. The young group consisted of men who were less than 35 years-old, and the middle-age group consisted of men who were more than 45 years-old. Results: The two groups had no significant differences in sperm concentration ([89.9±59.4]×106/mL vs. [104.4±82.1]×106/mL, p=0.108) or sperm morphology (normal forms: 3.6%±1.5% vs. 3.4%±1.6%, p=0.131). However, the middle-age group had a smaller semen volume (3.2±1.5 mL vs. 2.5±1.4 mL, p

Purpose: This systematic review and meta-analysis investigated the sperm retrieval rate (SRR) and pregnancy rate after testicular sperm extraction in men with azoospermia and those with a history of cryptorchidism treated by orchiopexy. Materials and Methods: The SRR and clinical pregnancy rate were investigated. We performed a sub-analysis that included factors such as bilaterality, age, and idiopathic non-obstructive azoospermia (iNOA). The analysis comprised 13 studies from January 1995 to July 2021. The data sources were PubMed/MEDLINE, Embase, and the Cochrane Library included “cryptorchidism”, “orchidopexy”, “azoospermia”, and “testicular sperm extraction”. Results: The overall mean SRR was 63.3% (95% confidence interval [CI], 57.6%–68.6%; I2=62.4%), and the overall mean clinical pregnancy rate was 30.1% (95% CI, 22.6%–38.8%; I2=69.9%). The meta-analysis comparing the SRR, there was no significant difference between patients with a history of bilateral and unilateral orchiopexy (relative risk [RR]=1.02; 95% CI, 0.89–1.16; p=0.79). Orchiopexy performed under the age of 10 years showed significantly increased SRR compared to the age of over 10 years (RR=1.25; 95% CI, 1.06–1.47; p=0.008). Azoospermic men with a history of cryptorchidism treated by orchiopexy had significantly higher SRR than iNOA (RR=1.90; 95% CI, 1.40–2.58; p

Purpose: Despite the role of carbon monoxide in ameliorating ischemia-reperfusion injury (IRI), its use in the clinical setting is restricted owing to its toxicity. Herein, we investigated the in vivo effects of carbon monoxide–releasing molecule-3 (CORM-3) on IRI. Materials and Methods: Fifteen rats were equally and randomly divided into three groups: sham (right nephrectomy), control (right nephrectomy and left renal ischemia), and CORM-3 (right nephrectomy and CORM-3 injection before left renal ischemia). Kidney tissues and blood samples collected from sacrificed rats were evaluated to determine the renoprotective effect and mechanism of CORM-3. Results: Concentrations of serum creatinine and kidney injury molecule-1 in the CORM-3 group were significantly lower than in the control group after 75 minutes of IRI (1.2 vs. 2.4 mg/dL, p=0.01, and 292 vs. 550 pg/mL, p

KoreaPurpose: We evaluated the usefulness of a home-based device (SwimCountTM) compared with World Health Organization (WHO) 5th semen analysis in screening for male fertility in Asian men.Materials and Methods: One hundred Asian men who visited CHA Seoul Station Fertility Center for evaluation of fertility were included. Semen samples were analyzed and compared with the SwimCountTM results. An aliquot of 0.5 mL of the semen sample was added to the SwimCountTM and a WHO 5th semen analysis was performed. Results were categorized as low (

Non-obstructive azoospermia is a major clinical issue associated with male infertility that remains to be addressed. Although neogenin is reportedly abundantly expressed in the testis, its role in mammalian spermatogenesis is unknown. We systematically investigated the role of neogenin during spermatogenesis by performing loss-of-function studies. Testis-specific neogenin conditional knock-out (cKO) mice were generated using CRISPR/Cas9 and neogenin-targeting guide RNAs. We analyzed the expression profiles of germ cell factors by RT-PCR and Western blotting. Neogenin localized mainly to spermatogonia in seminiferous tubules of mouse testes. RT-PCR and Western blot analyses further demonstrated that neogenin expression varied during spermatogenesis and was dramatically increased at postnatal day 12–25 during the pubertal stage. In neogenin-cKO mouse testes, the ratio of primary and secondary spermatocytes was significantly decreased compared with the control, while the number of apoptotic testicular cells was significantly increased. Taken together, these results suggest that neogenin plays a pivotal role in the maintenance and proliferation of spermatogonia during the early stage of spermatogenesis in mice.

Purpose: Sperm cryopreservation before cancer treatment is the most effective method to preserve the fertility of male pa-tients. We present our 21 years experience with sperm cryopreservation for cancer patients, including an examination of se-men quality, the current status of cryopreserved sperm, and the rate of sperm use for assisted reproductive technology (ART). Materials and Methods: A total of 721 cancer patients at Fertility Center of CHA Gangnam Medical Center successfully per-formed sperm cryopreservation for fertility preservation from January 1996 to December 2016. Medical chart review was used to analyze patient age, marital status, cancer type, semen volume, sperm counts and motility, length of storage, and cur-rent banking status. Results: The major cancers of the 721 patients were leukemia (28.4%), lymphoma (18.3%), testis cancer (10.0%). The mean age at cryopreservation was 27.0 years, and 111 patients (15.4%) performed sperm cryopreservation during or after cancer treatment. The mean sperm concentration was 66.7±66.3 ×106/mL and the mean sperm motility was 33.8%±16.3%. During median follow-up duration of 75 months (range, 1–226 months), 44 patients (6.1%) used their banked sperm at our fertility center for ART and 9 patients (1.2%) transferred their banked sperm to another center. The median duration from cryopreser-vation to use was 51 months (range, 1–158 months). Conclusions: Sperm cryopreservation before gonadotoxic treatment is the most reliable method to preserve the fertility of male cancer patients. Sperm cryopreservation should be offered as a standard of care for all men planning cancer therapy.

This study comprises a systematic review and meta-analysis of microsurgical vasoepididymostomy outcomes in epididymal obstructive azoospermia. A comprehensive literature search was performed using Medline, Embase, and the Cochrane library that included all studies related to microsurgical vasoepididymostomy. Keywords included “vasoepididymostomy,” “epididymovasostomy,” “epididymal obstruction,” and “epididymis obstruction.” Event rate and risk ratio (RR) were estimated. Patency rate and pregnancy rate were investigated. The analysis comprised 1422 articles, including 42 observational studies with 2298 enrolled patients performed from November 1978 to January 2017. The overall mean patency rate was 64.1% (95% confidence interval [CI]: 58.5%–69.3%; I2=83.0%), and the overall mean pregnancy rate was 31.1% (95% CI: 26.9%–35.7%; I2=73.0%). We performed a meta-analysis comparing the patency rate of bilateral microsurgical vasoepididymostomy and unilateral microsurgical vasoepididymostomy and found an RR of 1.38% (95% CI: 1.21%–1.57%; P < 0.00001). A comparison of the site of microsurgical vasoepididymostomy showed that caudal or corpus area was favorable for patency rate (RR = 1.17%; 95% CI: 1.01%–1.35%; P = 0.04). Patients with motile sperm in epididymal fluid exhibited an RR of 1.53% (95% CI: 1.11%–2.13%; P = 0.01) with respect to patency rate. Microsurgical vasoepididymostomy is an effective treatment for epididymal obstructive azoospermia that can improve male fertility. We find that performing microsurgical vasoepididymostomy bilaterally, anastomosing a larger caudal area, and containing motile sperm in epididymis fluid can potentially achieve a superior patency rate.

This study explored the association between built environment and semen parameters among men who sought fertility evaluation. We used a data of 5,886 men living in the Seoul capital area whose semen was tested at a single fertility center during 2016-2018. Distance to fresh water, the coast, major roadways, and neighborhood greenness measured by Normalized Difference Vegetation Index (NDVI) were evaluated. Outcome indicators were semen volume, sperm concentration, percentage of progressive motility, vitality, normal morphology, and total motile sperm count. Linear regression models were fitted to standardized values of six semen indicators. Majority of men were white-collar, clerical, and service workers. Linear associations between built environment features and semen quality indicators were not evident except for NDVI within 500 m and sperm vitality (β = 0.05; 95% confidence interval (CI): 0.01, 0.09). The 2nd quartile of distance to fresh water was associated with lower progressive motility compared to the 1st quartile (β = -0.10; 95% CI: -0.17, -0.03). Proportion of vitality was higher among men in the 2nd quartile of distance to roadways than those in the 1st quartile (0.08; 95% CI: 0.01, 0.15). Men in the 2nd quartile of NDVI had higher total motile sperm count (0.09; 95% CI: 0.01, 0.17). In the multi-exposure model, the positive association between NDVI and vitality remained (0.03; 95% CI: 0.00, 0.06). We observed potential evidence regarding the impact of built environment on male fertility, specifically a positive association between residential greenness and sperm vitality among men with a history of infertility.

Background and objective A small supernumerary marker chromosome (sSMC) is a rare structurally abnormal chromosome in which no part can be identified by conventional cytogenetic banding technique. There is little known about the association of marker chromosomes with male infertility. We performed a molecular cyto-genetic characterization sSMCs and investigated their association with male infertility. Methods Among 4230 infertile male patients who underwent cytogenetic analyses from January 2008 to December 2018, the records of 15 patients who were diagnosed with sSMCs were reviewed. After ini-tial infertility evaluation, the patients received additional genetic tests including G-bands by trypsin using Giemsa (GTG-banding), Nucleolar organizer region (NOR) banding, Fluorescence in situ hybridization (FISH), and array comparative genomic hybridization (aCGH) analyses to further char-acterize and identify the origin of their marker chromosome. Testis biopsy was performed for the azoospermic patients to evaluate spermatogenic status. Results Among 15 infertile males with sSMCs, eight had nonobstructive azoospermia, five had severe oligozo-ospermia, and two had sperm concentrations above the lower normal limit. The marker chromosomes were identified as Y ring chromosomes (n = 8), an isodicentric Y chromosome (n = 1), a neocen-tromere Y chromosome (n = 1), a derivative chromosome 1 (n = 1), and an acrocentric short arms (n = 4). Conclusion Marker chromosomes appear to be a rare genetic cause of male infertility. Additional cytogenetic tests, including NOR banding, FISH, and aCGH, could help to characterize the origin of the marker chromosome. Appropriate genetic counseling for couples with infertility caused by a marker chromo-some should be recommended.

Sperm motility is a crucial factor for normal fertilisation that is partly supported by mitochondrial activity. Enzymatic biofuel cells (EBFCs) generate electric currents by an electron grade from anodic to cathodic electrodes in a culture media. We demonstrate that electrical stimulation by EBFC at the nano-Ampere range enhances sperm motility that can potentially allow the development of a new therapeutic tool for male infertility, including poor motility. EBFC was set up with three different electrical currents (112 nA/cm2 and 250 nA/cm2) at two different times (1 h, 2 h). Each sample was evaluated for its motility by computer-assisted sperm analyses and sperm viability testing. In the expanded study, we used the optimal electrical current of the EBFC system to treat asthenozoospermia and sperm with 0% motility. Results showed that optimal electrical stimulation schemes with EBFCs enhanced sperm motility by 30-40% compared with controls. Activated spermatozoa led to tyrosine phosphorylation in the tail area of the sperm following the electrical stimulation in the nano-Ampere range. However, the electrically stimulated group did not exhibit increased acrosomal reaction rates compared with the control group. In cases related to asthenozoospermia, 40% of motility was recovered following the electrical stimulation at the nano-Ampere range. However, motility is not recovered in sperm with 0% motility. In conclusion, we found that sperm motility was enhanced by exposure to electrical currents in the nano-Ampere range induced by optimal EBFCs. Electrical stimulation enhanced the motility of the sperm though tyrosine phosphorylation in spermatozoa. Therefore, our results show that electrical currents in the nano-Ampere range can be potentially applied to male infertility therapy as enhancers of sperm motility in assisted reproductive technology.

With increased population and urban development, there are growing concerns regarding health impacts of environmental noise. We assessed the relationship between nighttime environmental noise and semen quality of men who visited for fertility evaluation. This is a retrospective cohort study of 1,972 male patient who had undertaken semen analysis between 2016-2018 at a single fertility center of Seoul, South Korea. We used environmental noise data of National Noise Information System (NNIS), Korea. Using semiannual nighttime noise measurement closest to the time of semen sampling, individual noise exposures at each patient's geocoded address were estimated with empirical Bayesian kriging method. We explored the association between environmental noise and semen quality indicators (volume, concentration, % of progressive motility, vitality, normal morphology, total motile sperm count, oligozoospermia, asthenozoospermia, and severe teratozoospermia) using multivariable regression and generalized additive models. Estimated exposure to nighttime environmental noise level in the study population was 58.3±2.2 Leq. Prevalence of oligozoospermia, asthenozoospermia, and severe teratozoospermia were 3.3%, 14.0%, and 10.1%. Highest quartile nighttime noise was associated with 3.5 times higher odds of oligozoospermia (95% CI: 1.18, 10.17) compared to lowest quartile. In men whose noise exposure is in 3rd quartile, odds ratio (OR) of severe teratozoospermia was 0.57 (95% CI: 0.33, 0.98). The OR for 4th quartile noise were toward null. In generalized additive model, the risk of oligozoospermia increases when the nighttime noise is 55 Leq dB or higher. Our study adds an evidence of potential impact of environmental noise on semen quality in men living in Seoul. Additional studies with more refined noise measurement will confirm the finding.

Emerging evidence has suggested that cytoreductive prostatectomy (CRP) allows superior oncologic control when compared to current standard of care androgen deprivation therapy alone. However, the safety and benefit of cytoreduction in metastatic prostate cancer (mPCa) has not been proven. Therefore, we evaluated the incidence of complications following CRP in men newly diagnosed with mPCa. A total of 68 patients who underwent CRP from 2006 to 2014 at four tertiary surgical centers were compared to 598 men who underwent radical prostatectomy for clinically localized prostate cancer (PCa). Urinary incontinence was defined as the use of any pad. CRP had longer operative times (200 min vs 140 min, P < 0.0001) and higher estimated blood loss (250 ml vs 125 ml, P < 0.0001) compared to the control group. However, both overall (8.82% vs 5.85%) and major complication rates (4.41% vs 2.17%) were comparable between the two groups. Importantly, urinary incontinence rate at 1-year after surgery was significantly higher in the CRP group (57.4% vs 90.8%, P < 0.0001). Univariate logistic analysis showed that the estimated blood loss was the only independent predictor of perioperative complications both in the unadjusted model (OR: 1.18; 95% CI: 1.02-1.37; P = 0.025) and surgery type-adjusted model (OR: 1.17; 95% CI: 1.01-1.36; P = 0.034). In conclusion, CRP is more challenging than radical prostatectomy and associated with a notably higher incidence of urinary incontinence. Nevertheless, CRP is a technically feasible and safe surgery for selecting PCa patients who present with node-positive or bony metastasis when performed by experienced surgeons. A prospective, multi-institutional clinical trial is currently underway to verify this concept.

When ejaculated sperm travels through the vagina to the uterus, mucus secreted by the cervical canal generally filters out sperm having low motility and poor morphology. To investigate this selection principle in vivo, we developed a microfluidic sperm-sorting chip with a viscous medium (polyvinylpyrrolidone: PVP) to imitate the biophysical environment mimic system of the human cervical canal. The material property of the PVP solution was tuned to the range of viscosities of cervical mucus using micro-viscometry. The selection of high-quality human sperm was experimentally evaluated in vitro and theoretically analyzed by the convection-diffusion mechanism. The convection flow is shown to be dominant at low viscosity of the medium used in the sperm-sorting chip when seeded with raw semen; hence, the raw semen containing sperm and debris convectively flow together with suppressed relative dispersions. Also, it was observed that the sperm selected via the chip not only had high motilities but also normal morphologies and high DNA integrity. Therefore, the biomimetic sperm-sorting chip with PVP medium is expected to improve male fertility by enabling the selection of high-quality sperm as well as uncovering pathways and regulatory mechanisms involved in sperm transport through the female reproductive tract for egg fertilization.

Purpose: To assess the effectiveness and safety of robot-assisted radical prostatectomy (RARP) versus laparoscopic radical prostatectomy (LRP) in the treatment of prostate cancer. Materials and Methods: Existing systematic reviews were updated to investigate the effectiveness and safety of RARP. Electronic databases, including Ovid MEDLINE, Ovid Embase, the Cochrane Library, KoreaMed, Kmbase, and others, were searched through July 2014. The quality of the selected systematic reviews was assessed by using the revised assessment of multiple systematic reviews (R-Amstar) and the Cochrane Risk of Bias tool. Meta-analysis was performed by using Revman 5.2 (Cochrane Community) and Comprehensive Meta-Analysis 2.0 (CMA; Biostat). Cochrane Q and I2 statistics were used to assess heterogeneity. Results: Two systematic reviews and 16 additional studies were selected from a search performed of existing systematic reviews. These included 2 randomized controlled clinical trials and 28 nonrandomized comparative studies. The risk of complications, such as injury to organs by the Clavien-Dindo classification, was lower with RARP than with LRP (relative risk [RR], 0.44; 95% confidence interval [CI], 1.23–0.85; p=0.01). The risk of urinary incontinence was lower (RR, 0.43; 95% CI, 0.31–0.60; p

Context: The twigs of Sorbus alnifolia (Sieb. et Zucc.) K. Koch (Rosaceae) have been used to treat neurological disorders as a traditional medicine in Korea. However, there are limited data describing the efficacy of S. alnifolia in Parkinson’s disease (PD). Objective: This study was conducted to identify the protective effects of the methanol extracts of S. alnifolia (MESA) on the dopaminergic (DA) neurodegeneration in Caenorhabditis elegans. Materials and methods: To test the neuroprotective action of MESA, viability assay was performed after 48 h exposure to 1-methyl-4-phenylpyridine (MMP+) in PC12 cells and C. elegans (400 μM and 2 mM of MMP+, respectively). Fluorescence intensity was quantified using transgenic mutants such as BZ555 (Pdat-1::GFP) and and UA57 (Pdat-1::GFP and Pdat-1::CAT-2) to determine MESA’s effects on DA neurodegeneration in C. elegans. Aggregation of α-synuclein was observed using NL5901 strain (unc-54p::α-synuclein::YFP). MESA’s protective effects on the DA neuronal functions were examined by food-sensing assay. Lifespan assay was conducted to test the effects of MESA on the longevity. Results: MESA restored MPP+-induced loss of viability in both PC12 cells and C. elegans (85.8% and 54.9%, respectively). In C. elegans, MESA provided protection against chemically and genetically-induced DA neurodegeneration, respectively. Moreover, food-sensing functions were increased 58.4% by MESA in the DA neuron degraded worms. MESA also prolonged the average lifespan by 25.6%. However, MESA failed to alter α-synuclein aggregation. Discussion and conclusions: These results revealed that MESA protects DA neurodegeneration and recovers diminished DA neuronal functions, thereby can be a valuable candidate for the treatment of PD.

We present a 61-year-old man who was diagnosed with synchronous prostate cancer and suspicious renal cell carcinoma of the right kidney, treated with combined Retzius-sparing robot-assisted radical prostatectomy (RS-RARP) and robot-assisted partial nephrectomy (RAPN). The combined approach using RS-RARP and RAPN is technically feasible and safe surgical option for treatment of concomitant prostate cancer and suspicious renal cell carcinoma.

Human microbiota is heavily involved in host health, including the aging process. Based on the hypothesis that the human microbiota manipulates host aging via the production of chemical messengers, lifespan-extending activities of the metabolites produced by the oral commensal bacterium Corynebacterium durum and derivatives thereof were evaluated using the model organism Caenorhabditis elegans. Chemical investigation of the acetone extract of a C. durum culture led to the identification of monoamines and N-acetyl monoamines as major metabolites. Phenethylamine and N-acetylphenethylamine induced a potent and dose-dependent increase of the C. elegans lifespan, up to 21.6% and 19.9%, respectively. A mechanistic study revealed that the induction of SIR-2.1, a highly conserved protein associated with the regulation of lifespan, was responsible for the observed increased longevity.

Here in this study, we isolated 4-hydroxybenzoic acid (4-HBA) from Veronica peregrina and elucidated the anti-aging effect of 4-HBA using Caenorhabditis elegans model system. 4-HBA showed potent lifespan extension in C. elegans under normal culture condition. This compound also exhibited significant increase in stress resistance against osmotic, heat, and oxidative stress conditions. In addition, superoxide dismutase and catalase activities were up-regulated by 4-HBA treatment, resulted in reduced intracellular ROS levels. We also investigated the expression levels of SOD-3 and HSP-16.2 using transgenic strains, and both of them were significantly increased by 4-HBA treatment. Further studies on the aging-related factors revealed that 4-HBA may affect reproduction but not body size and pharyngeal pumping of nematodes. Moreover, 4-HBA fed worms showed increased body movements and decreased lipofuscin accumulation compared to control worms, indicating 4-HBA affects age-associated changes in C. elegans. Our mechanistic studies revealed that there was no significant lifespan extension in 4-HBA-treated sir-2.1 and daf-16 null mutants, indicating they are involved in 4-HBA-mediated lifespan regulation. Our findings suggest that 4-HBA treatment confers increased longevity and stress resistance in C. elegans through not only its strong antioxidant capacity, but also SIR-2.1/SIR2-mediated DAF-16/FOXO activation, independent of dietary restriction and insulin/IGF signaling pathway.

PURPOSE/OBJECTIVES:To investigate pN1 prostate cancer (PCa) patients treated surgically without immediate adjuvant treatment. MATERIALS AND METHODS:We analyzed the database of 2316 patients at our institution who underwent robot-assisted radical prostatectomy (RARP)/radical prostatectomy (RP) between July 2005 and November 2012. 87 patients with pN1 PCa and received no neoadjuvant and immediate adjuvant therapy were included in the study. Included pN1 PCa patients were followed up for median of 60 months. Biochemical recurrence (BCR)-free survival, metastasis-free survival (MFS), cancer specific survival (CSS), and overall survival (OS) rates were determined by using Kaplan-Meier analysis. Cox regression analysis was performed to investigate the impact of prostate-specific antigen (PSA) level, Gleason score, extraprostatic extension, seminal vesicle invasion, perineural invasion, lymphovascular invasion, positive surgical margin, tumor volume, early post-operative PSA(6 weeks), PSA nadir, lymph node yield, and number of pathologically positive lymph nodes on survival. RESULTS:The 5-year OS rate of patients was 86.1%, while the CSS rate was 89.6%. The metastasis-free and BCR-free survival rates were 71% and 19.1%, respectively, and each was significantly correlated with the number of positive lymph nodes on log rank tests (p = 0.004 and p = 0.039, respectively). The presence of 2 or more pathologically positive LNs (HR:2.20; 95% CI 1.30-3.72; p = 0.003) and a Gleason score ≥8 (HR: 2.40;95% CI: 1.32-4.38; p = 0.04) were significant negative predictors of BCR free survival on multivariable regression analysis. Furthermore, the presence of 2 or more positive lymph nodes (HR: 1.06; 95% CI 1.01-1.11; p = 0.029) were significant negative predictors of metastasis-free survival on multivariable regression analysis. Additionally, in the patients who had no BCR without adjuvant treatment 9 patients out of 10 (90%) had single positive LN and 5 patients out of 10 (50%) had Gleason score 7. Therefore, single positive LN, and Gleason scores ≤7 have significantly low risk of disease progression. CONCLUSIONS:pN1 PCa patients have heterogenous clinical courses. Patients with single positive LN, and Gleason scores ≤7 have low risk of recurrence. Close observation with delayed adjuvant hormone therapy can be considered in these patients.

To investigate the feasibility of RAPN on T1b renal mass by assessment of Trifecta and Pentafecta rate between T1a and T1b renal mass.We retrospectively reviewed the medical records of 277 cases of RPN performed from 2006 to 2015. Sixty patients with clinically T1b renal masses (> 4 cm and ≤ 7 cm) were identified, and from 180 patients with clinically T1a renal mass, 60 patients were matched with T1b renal mass by propensity score. Tumor complexity was investigated according to R.E.N.A.L nephrometry score. "Pentafecta" was defined as achievement of Trifecta (negative surgical margin, no postoperative complications and warm ischemia time of ≤ 25 minutes) with addition of over 90% estimated GFR preservation and no chronic kidney disease stage upgrading at 1 year postoperative period. Propensity score matching was performed by OneToManyMTCH. Logistic regression models were used to identify the variables which predict the Trifecta, and Pentafecta ac.Preoperative variables (age, sex, body mass index, ASA score) were similar between T1a and T1b after propensity score matching. The median R.E.N.A.L. nephrometry score was 8 vs 9 for T1a and T1b respectively (p

BACKGROUND:The aim of this study is to determine anti-cancer effect of Icariside II purified from the root of Epimedium koreanum Nakai on human acute myeloid leukemia (AML) cell line U937. METHODOLOGY/PRINCIPAL FINDINGS:Icariside II blocked the growth U937 cells in a dose- and time-dependent manner. In this anti-proliferation process, this herb compound rendered the cells susceptible to apoptosis, manifested by enhanced accumulation of sub-G1 cell population and increased the terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)-positive cells. Icariside II was able to activate caspase-3 and cleaved poly (ADP-ribose) polymerase (PARP) in a time-dependent manner. Concurrently, the anti-apoptotic proteins, such as bcl-x(L) and survivin in U937 cells, were downregulated by Icariside II. In addition, Icariside II could inhibit STAT3 phosphorylation and function and subsequently suppress the activation of Janus activated kinase 2 (JAK2), the upstream activators of STAT3, in a dose- and time-dependent manner. Icariside II also enhanced the expression of protein tyrosine phosphatase (PTP) SH2 domain-containing phosphatase (SHP)-1, and the addition of sodium pervanadate (a PTP inhibitor) prevented Icariside II-induced apoptosis as well as STAT3 inactivation in STAT3 positive U937 cells. Furthermore, silencing SHP-1 using its specific siRNA significantly blocked STAT3 inactivation and apoptosis induced by Icariside II in U937 cells. CONCLUSIONS/SIGNIFICANCE:Our results demonstrated that via targeting STAT3-related signaling, Icariside II sensitizes U937 cells to apoptosis and perhaps serves as a potent chemotherapeutic agent for AML.

ABSTRACT Introduction and objectives Nephroureterectomy remains the gold standard treatment option for upper tract tumors. However, segmental ureterectomy may be another option in patients with single kidney, borderline renal function or high medical comorbidities. The aim of this video is to assess the feasibility of robotic surgery as a minimally invasive technique in treatment of a high comorbid patient with ureteric tumor. Materials and Methods Eighty-year old male patient, with a medical history of chronic hypertensive and uncontrolled Diabetes Mellitus, was referred to our department for treatment of ureteric tumor. Patient underwent robot-assisted radical prostatectomy 5 years ago. Patient’s Charlson comorbidity index score was 9. Computed tomography showed a 2.5cm right ureteral luminal filling enhancing lesion at lower part of upper 1/3 ureter. We performed diagnostic flexible cystoscopy under local anesthesia to exclude associated lower urinary tract carcinoma, and bladder wash was negative for malignancy. Under general anesthesia patient underwent diagnostic flexible ureteroscopy to confirm mass location, and a retrograde pyelography to rule out additional tumors on the right collecting system. Then, the patient was placed in the full lateral flank position without Table flexion. Ports placement were inserted as follow: a “12mm” optical trocar at pararectal line superior and lateral to umbilicus, two “8mm” robotic trocars cranial and caudal to optical trocar (8cm distance), a “8mm” robotic trocar towards anterior superior ischial spine, and a “12mm” assistant trocar was inserted between umbilicus and pubic bone. The surgical steps are shown in the video. Results The procedure was performed easily. The total operative time and consol time were 100 and 60 minutes, respectively. Blood loss was 50ml. No reported intraoperative or postoperative complications. Notably, we took full precautions in case of intraoperative failure to complete the procedure successfully, nephroureterectomy was our second option. Postoperative serum creatinine was 1.2mg/dL and length of hospital stay was 2 days. The frozen biopsy showed that the tumor was resected with safe proximal and distal surgical margins. Final histopathology revealed high grade (G3) urothelial carcinoma (pT3), measures (1.3x1.2x0.2cm), associated with carcinoma in situ. Conclusion We affirm that robotic segmental ureterectomy and ureteroureterostomy could be offered safely as a minimally invasive treatment for patients with ureteric tumors and high-risk medical comorbidities. It provides excellent perioperative outcomes and early oncological safety with regard to surgical margins.