Structure-Activity Relationship of Oleanane-Type Pentacyclic Triterpenoids on Nuclear Factor κB Activation and Intracellular Trafficking and N-Linked Glycosylation of Intercellular Adhesion Molecule-1.

In our previous study, two oleanane-type pentacyclic triterpenoids (oleanolic acid and maslinic acid) were reported to affect the N-glycosylation and intracellular trafficking of intercellular adhesion molecule-1 (ICAM-1). The present study was aimed at investigating the structure-activity relationship of 13 oleanane-type natural triterpenoids with respect to the nuclear factor κB (NF-κB) signaling pathway and the expression, intracellular trafficking, and N-glycosylation of the ICAM-1 protein in human lung adenocarcinoma A549 cells. Hederagenin, echinocystic acid, erythrodiol, and maslinic acid, which all possess two hydroxyl groups, decreased the viability of A549 cells. Celastrol and pristimerin, both of which possess an α,ß-unsaturated carbonyl group, decreased cell viability but more strongly inhibited the interleukin-1α-induced NF-κB signaling pathway. Oleanolic acid, moronic acid, and glycyrrhetinic acid interfered with N-glycosylation without affecting the cell surface expression of the ICAM-1 protein. In contrast, α-boswellic acid and maslinic acid interfered with the N-glycosylation of the ICAM-1 protein, which resulted in the accumulation of high-mannose-type N-glycans. Among the oleanane-type triterpenoids tested, α-boswellic acid and maslinic acid uniquely interfered with the intracellular trafficking and N-glycosylation of glycoproteins.

Cucurbitacin B Down-Regulates TNF Receptor 1 Expression and Inhibits the TNF-α-Dependent Nuclear Factor κB Signaling Pathway in Human Lung Adenocarcinoma A549 Cells.

Pro-inflammatory cytokines, such as tumor necrosis factor-α (TNF-α), induce the expression of intracellular adhesion molecule-1 (ICAM-1) by activating the nuclear factor κB (NF-κB) signaling pathway. In the present study, we found that cucurbitacin B decreased the expression of ICAM-1 in human lung adenocarcinoma A549 cells stimulated with TNF-α or interleukin-1α. We further investigated the mechanisms by which cucurbitacin B down-regulates TNF-α-induced ICAM-1 expression. Cucurbitacin B inhibited the nuclear translocation of the NF-κB subunit RelA and the phosphorylation of IκBα in A549 cells stimulated with TNF-α. Cucurbitacin B selectively down-regulated the expression of TNF receptor 1 (TNF-R1) without affecting three adaptor proteins (i.e., TRADD, RIPK1, and TRAF2). The TNF-α-converting enzyme inhibitor suppressed the down-regulation of TNF-R1 expression by cucurbitacin B. Glutathione, N-acetyl-L-cysteine, and, to a lesser extent, L-cysteine attenuated the inhibitory effects of cucurbitacin B on the TNF-α-induced expression of ICAM-1, suggesting that an α,ß-unsaturated carbonyl moiety is essential for anti-inflammatory activity. The present results revealed that cucurbitacin B down-regulated the expression of TNF-R1 at the initial step in the TNF-α-dependent NF-κB signaling pathway.

Bioactive Evaluation of Ursane-Type Pentacyclic Triterpenoids: ß-Boswellic Acid Interferes with the Glycosylation and Transport of Intercellular Adhesion Molecule-1 in Human Lung Adenocarcinoma A549 Cells.

Ursane-type pentacyclic triterpenoids exert various biological effects, including anticancer and anti-inflammatory activities. We previously reported that ursolic acid, corosolic acid, and asiatic acid interfered with the intracellular trafficking and glycosylation of intercellular adhesion molecule-1 (ICAM-1) in human lung adenocarcinoma A549 cells stimulated with the pro-inflammatory cytokine interleukin-1α. However, the structure-activity relationship of ursane-type pentacyclic triterpenoids remains unclear. In the present study, the biological activities of seven ursane-type pentacyclic triterpenoids (ß-boswellic acid, uvaol, madecassic acid, 3-O-acetyl-11-keto-ß-boswellic acid, ursolic acid, corosolic acid, and asiatic acid) were investigated. We revealed that the inhibitory activities of ursane-type pentacyclic triterpenoids on the cell surface expression and glycosylation of ICAM-1 and α-glucosidase activity were influenced by the number of hydroxy groups and/or the presence and position of a carboxyl group. We also showed that ß-boswellic acid interfered with ICAM-1 glycosylation in a different manner from other ursane-type pentacyclic triterpenoids.

Properties of Achromobacter xylosoxidans highly resistant to aminoglycoside antibiotics.

We herein discovered a highly resistant clinical isolate of Pseudomonas aeruginosa with MICs to amikacin, gentamicin, and arbekacin of 128 µg/mL or higher in a drug sensitivity survey of 92 strains isolated from the specimens of Yoka hospital patients between January 2009 and October 2010, and Achromobacter xylosoxidans was separated from this P. aeruginosa isolate. The sensitivity of this bacterium to 29 antibiotics was investigated. The MICs of this A. xylosoxidans strain to 9 aminoglycoside antibiotics were: amikacin, gentamicin, arbekacin, streptomycin, kanamycin, neomycin, and spectinomycin, 1,024 µg/mL or ≥ 1,024 µg/mL; netilmicin, 512 µg/mL; and tobramycin, 256 µg/mL. This strain was also resistant to dibekacin. This aminoglycoside antibiotic resistant phenotype is very rare, and we are the first report the emergence of A. xylosoxidans with this characteristic.

Evaluating Non-ablative Erbium Yttrium Aluminium Garnet (YAG) Laser Treatment for Polypropylene Mesh-Induced Vaginal Erosion: A Case Series.

Background Vaginal erosion caused by the polypropylene mesh is a serious side effect, and the development of effective treatment methods is required. This study explored the potential of non-ablative vaginal erbium yttrium aluminum garnet (YAG) laser treatment (VEL) as a novel treatment approach. Methods In this study, VEL was performed on nine women who experienced vaginal erosion after undergoing treatment for pelvic organ prolapse (POP) with polypropylene mesh. These patients visited our hospital between April and December 2020. Using the Renovalase (SP Dynamis Fotona d.o.o., Ljubljana, Slovenia), the laser was applied to the entire vagina, with intensive irradiation focused on the erosion areas. Detailed analyses of symptoms before and after treatment, as well as histopathological changes, were conducted one year post-treatment. Results Nine women were referred to our hospital due to vaginal erosion caused by polypropylene mesh. The participants' average age was 73.2 years (range: 69-81 years), with four patients having undergone transvaginal mesh (TVM) surgery and five undergoing laparoscopic sacrocolpopexy (LSC). The average time from mesh insertion to treatment initiation was 7.2 years (range: 3-15 years), with eight patients having previously attempted mesh removal. Post-treatment, significant improvements were observed in managing vaginal erosion and related bleeding, corroborated by histopathological analysis confirming cell regeneration and tissue repair. These improvements also resulted in significant improvements in bleeding management and quality of life (QoL). Conclusion VEL suggests the possibility of being an effective treatment method for vaginal erosion caused by a polypropylene mesh. However, further research is needed because of the small sample size and the limitations inherent in the retrospective case series design.

Laser Treatment for Patients With Vulvodynia and Interstitial Cystitis/Bladder Pain Syndrome: A Case Series (The UNICORN-3 Study).

Introduction Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic pain disorder characterized by urgency, frequency of urination, and pelvic pain. Women with IC/BPS often experience sexual dysfunction, vulvodynia, and vaginal health issues. Combined erbium and neodymium yttrium aluminum garnet (YAG) laser treatments targeting the vagina and vulva have shown promise in improving symptoms. Our study aims to investigate the effectiveness of these combined laser treatments in women with IC/BPS and vulvodynia. Methods Women diagnosed with vulvodynia and IC/BPS underwent combined laser treatment using vaginal erbium:YAG laser (VEL) and neodymium:YAG laser (Nd:YAG). Various parameters were evaluated, including the vulvodynia test, numeric rating scale (NRS-11) for pain, interstitial cystitis symptom index and problem index (ICSI and ICPI), pelvic pain and urgency/frequency symptom score (PUF), and mean urination volume/daily urination frequency in a three-day urination diary. Treatment was administered three times, with intervals of one month between each session, and follow-up evaluations were conducted at six and 12 months. All statistical analyses were designed and programmed by the AI chatbot GPT-4 (chatGPT-4). Results Fifteen female patients diagnosed with vulvodynia and IC/BPS were treated with three sessions of VEL + Nd:YAG. Significant improvements were observed in the vulvodynia test, NRS-11 scores, PUF, ICSI scores, ICPI scores, mean urination volume, and daily urination frequency at six and 12 months (p<0.01). Short-term improvements in IC/BPS pain scores correlated with improvements in the vulvodynia test (p=0.007), suggesting a synergistic effect. However, no significant correlations were found at 12 months. Conclusion Combined laser treatments targeting the vagina and vulva showed significant therapeutic effects in women with IC/BPS and vulvodynia. The addition of Nd:YAG to the VEL treatment enhanced outcomes. Short-term improvements in IC/BPS pain scores correlated with improvements in the vulvodynia test, indicating a synergistic effect. Long-term improvements in both vulvodynia and IC/BPS symptoms may occur independently. These findings highlight the importance of comprehensive approaches for treating coexisting vulvodynia and IC/BPS.

Efficacy of Two Laser Treatment Strategies for Breast Cancer Survivors With Genitourinary Syndrome of Menopause.

Background A typical symptom of patients with genitourinary syndrome of menopause (GSM) is dyspareunia. Dyspareunia has been thought to be caused by vaginal dryness. In recent years, a survey of breast cancer survivors (BCS) with GSM has shown that para-hymen is the most painful. Dyspareunia and superficial vulvar pain (vulvodynia) may be closely linked. A recent study showed that vulvodynia is very common in BCS. Therefore, we believe treatment targeting the vagina and the vulva is necessary for pain in BCS with GSM. We hypothesized that treating both the vagina and the vulva would solve the problem of BCS with GSM. We compared the vaginal erbium SMOOTH mode laser (VEL) and neodymium-doped yttrium-aluminum-garnet (Nd:YAG) laser (VEL+Nd:YAG) combination treatment over time. This study explores therapeutic targets for pain in BCS with GSM. Methodology This retrospective, case-control study targeted sexually active BCS who reported GSM with vulvodynia and dyspareunia. After all women enrolled in the VEL treatment group had completed treatment, we treated women enrolled in the VEL+Nd:YAG treatment group. A total of 256 women who received either VEL+Nd:YAG or VEL were enrolled. Propensity score (PS)-matching analysis was used to compare two-year postoperative data retrospectively. The PS-matching results registered 102 patients in the VEL+Nd:YAG group and 102 patients in the VEL group. Symptoms were assessed using the visual analog scale (VAS) for vulvodynia before and after laser treatment for one, three, six, 12, and 24 months after completion. As a preliminary study, the vulvodynia swab test confirmed the causative location of dyspareunia. Moreover, the Female Sexual Function Index (FSFI) and Vaginal Health Index Score (VHIS) were assessed. FSFI and VHIS were treated as supplement research because the conditions were unmet. Results In the vulvodynia swab test, dyspareunia, and para-hymen (especially at 4 o'clock and 9 o'clock), all felt pain, and only a few felt pain in the vagina and labia. FSFI improved significantly in the VEL+Nd:YAG group and persisted for two years. VHIS improved equally in both groups and was not significantly different. After the first laser application, the VEL+Nd:YAG and the VEL groups showed sustained efficacy and safety in vulvodynia. Baseline VAS scores (8.74 ± 0.72 vs. 8.79 ± 0.74; p = 0.564) were similar in both groups. Both groups had a significant (p < 0.001) decrease in the VAS score. The VAS values in the VEL+Nd:YAG group and the VEL group decreased from the pretreatment to 3.79 ± 0.63 (p < 0.001 vs. baseline) and 5.56 ± 0.89 (p < 0.001 vs. baseline) after the third treatments, respectively. After 24 months, the VAS value in the VEL+Nd:YAG group and the VEL group was at 4.43 ± 1.38 (p < 0.001 vs. baseline) and 5.56 ± 0.89 (p < 0.001 vs. baseline), respectively. The side effects in both groups were short-term and minor. Conclusions Both VEL+NdYAG and VEL effectively and safely treat GSM dyspareunia and vulvodynia in BCS. Comparing the two groups, we confirmed that VEL+Nd:YAG treatment of the vaginal vestibule and vaginal opening reduced superficial vulvar pain more effectively, extensively, and over a longer period than VEL. The results of the vulvodynia swab test, FSFI, and VHIS suggest that the vulva and the vagina are important therapeutic targets for pain in BCS with GSM. The importance of treating the vulvar area for superficial pain and dyspareunia in GSM has been emphasized.

Predictive Factors for High Post-void Residual Volume in Older Females After OnabotulinumA Treatment for Severe Overactive Bladder Using a Machine Learning Model.

Introduction Intravesical onabotulinumA injection is actively used for the treatment of overactive bladder (OAB). However, it occasionally results in significant post-void residual urine (PVR) volume, which can lead to complications and can further impair the activities of daily living in older people. Therefore, this study aimed to identify the predictors of a high post-onabotulinumA injection PVR volume in older women with severe OAB. Methods An observational study was conducted on older women who had previously received intravesical onabotulinumA injections to treat OAB between 2020 and 2022. Urodynamic studies and symptom assessments were conducted, and machine learning models, including random forest and support vector machine (SVM) models, were developed using the R code generated by Chat Generative Pre-trained Transformer 4 (ChatGPT, OpenAI, San Francisco, USA). Results Among 128 patients with OAB, 23 (18.0%) had a PVR volume of > 200 mL after receiving onabotulinumA injections. The factors associated with a PVR volume of > 200 mL were investigated using univariate and multivariate analyses. Age, frailty, OAB-wet, daytime frequency, and nocturia were significant predictors. Random forest analysis highlighted daytime frequency, frailty, and voiding efficiency as important factors. An SVM model incorporating daytime frequency, frailty, and voiding efficiency improved PVR volume prediction. Logit(p) estimation yielded an area under the receiver operating characteristic curve of 0.926294.  Conclusion The study found daytime frequency, frailty, and voiding inefficiency to be significant factors associated with a PVR volume of > 200 mL, in older women with severe OAB. Utilizing advanced machine learning techniques and following the guidance of ChatGPT, this research emphasizes the relevance of considering multiple intersecting factors for predicting PVR volume. The findings contribute to our understanding of onabotulinumA injection treatment for OAB and support evidence-based decision-making using readily available information.

Improvement of gel properties of dried egg white by modification with galactomannan through the Maillard reaction.

The effects of Maillard reaction on gel properties of dried egg white (DEW) with galactomannan (GM) were investigated. Maillard-reacted DEW (MDEW) was prepared by dry-heating a mixture with a weight ratio of 1:4 of GM to DEW at 60 degrees C and 65% relative humidity. The modification of amino groups and polymerization of DEW proteins dry-heated with GM proceeded with increasing the dry-heating time. The covalent attachment of GM to DEW was confirmed from SDS-PAGE analysis. Gel strength and water-holding capacity of MDEW gels were higher than those of DEW dry-heated without GM (control DEW) and reached maximum after 3 days of dry-heating. The appearance of MDEW gels became transparent with increasing the dry-heating time, but control DEW gels were still turbid. MDEW dry-heated for 3 days was almost soluble even after heating of its solution at 90 degrees C, whereas control DEW proteins precipitated. The modification of DEW with GM through the Maillard reaction was an effective method to make a firm and transparent gel from DEW at broader range of pH and NaCl concentration of the medium.

Comparison of lumbar drainage and external ventricular drainage for clearance of subarachnoid clots after Guglielmi detachable coil embolization for aneurysmal subarachnoid hemorrhage.

OBJECTIVE: Subarachnoid clots play an important role in development of delayed vasospasm after subarachnoid hemorrhage (SAH). The purpose of this study was to compare clearance of subarachnoid clots using external ventricular drainage (EVD) or lumbar drainage (LD) after Guglielmi detachable coil (GDC) embolization for aneurysmal SAH. METHODS: The subjects were 51 treated with GDC coil embolization for aneurysmal Fisher group 3 SAH within 72 h of ictus. Software-based volumetric quantification of the subarachnoid clots was performed on CT scans and the hemoglobin (Hb) level was measured in CSF drained from each catheter. RESULTS: Clearance of subarachnoid clots was more rapid in patients treated with LD (n=34) compared to those treated with EVD (n=17). The Hb level in CSF was significantly higher in the LD group on Days 4-5 after onset of SAH (P<0.05), but was higher in the EVD group on Days 8-9. The incidence of symptomatic vasospasm did not differ between the two groups. The rate of occurrence of a new low density area on CT scans was higher in patients treated with EVD, but not significantly higher than the rate in the LD group. CONCLUSION: GDC embolization followed by lumbar drainage accelerates the reduction of subarachnoid clots, but EVD may contribute to stasis of hemorrhage within subarachnoid spaces.

Fate of clots in patients with subarachnoid hemorrhage after different surgical treatment modality: a comparison between surgical clipping and Guglielmi detachable coil embolization.

BACKGROUND: Subarachnoid clot is important in the development of delayed vasospasm after subarachnoid hemorrhage (SAH). OBJECTIVE: To compare the clearance of subarachnoid clot and the incidence of symptomatic vasospasm in surgical clipping and embolization with Guglielmi detachable coils for aneurysmal SAH. METHODS: The subjects were 115 patients with Fisher group 3 aneurysmal SAH on computed tomography scan at admission whose aneurysm was treated by surgical clipping (clip group; n = 86) or Guglielmi detachable coil embolization (coil group; n = 29) within 72 hours of ictus. Software-based volumetric quantification of the subarachnoid clot was performed, and the amount of hemoglobin in drained cerebrospinal fluid was measured. RESULTS: Clearance of the subarachnoid clot on the computed tomography scan was rapid in the clip group until the day after the operation but slow in the coil group (58.9% removed vs 27.8% removed; P = .008). However, postoperative clearance of the clot occurred more rapidly in the coil group. Reduction of the clot until days 3 through 5 did not differ significantly between the 2 groups (72.9% removed vs 75.2% removed). The amount of hemoglobin in the clip group was > 0.8 g/d until day 3 and then gradually decreased (n = 15), but hemoglobin in the coil group remained at > 0.8 g/d until day 5 (n = 17). The incidence of symptomatic vasospasm did not differ between the groups. CONCLUSION: Subarachnoid clot can be removed directly during surgical clipping, which is not possible with endovascular treatment. However, the percentage reduction of the clot on days 3 through 5 did not differ between the 2 groups.

Clinical significance of measuring blood coagulation factor XIIIA regularly and continuously in patients with Crohn's disease.

BACKGROUND: The aim of the present paper was to determine the mechanism by which the level of coagulation factor XIIIA declines during the active phase of Crohn's disease. METHODS: The relationship between the activity of Crohn's disease and factor XIIIA was observed in 31 patients with Crohn's disease prospectively. The relationship between factor XIIIA and thrombin-antithrombin III complex (TAT), factor XIIIA expressed on the surface of peripheral monocytes, was also evaluated. RESULTS: During the first year, there were 11 patients with Crohn's disease in the active phase and 20 patients who remained in remission. The average of the lowest level of factor XIIIA among the patients in the active phase was 60.1%. The average of the lowest level of factor XIIIA in patients who remained in remission was 78.1% (P = 0.049). Among the 20 patients who remained in remission for 1 year, eight patients had factor XIIIA levels below 70%. Six of them required surgical enterectomies, on average 2 years and 1 month later. However, none of the 12 patients who remained in remission for 1 year and who never had factor XIIIA levels <70% had a surgical enterectomy during follow up of 4 years and 6 months (P = 0.002). The decline of factor XIIIA was not due to increased consumption secondary to blood coagulation (TAT), nor was it due to a decline in the function of monocytes that produce factor XIIIA. CONCLUSION: Factor XIIIA declines during the active phase of Crohn's disease because it might be consumed in the repair of injured tissue.

Avaliaçäo dos aspectos pessoais ocupacionais e psicossociais, e sua relaçäo no surgimento e ou agravamento de lesöes músculo-esqueléticas em um setor de trabalho / Evaluation of the individual occupational and psychossocial, and its relation in the appearing and or intensity of musculoskeletal disorders in the work

O objetivo deste estudo foi avaliar os aspectos pessoais, físicos e biomecânicos ocupacionais e psicossociais da organizaçäo do trabalho e sua relaçäo no surgimento e ou agravamento de lesöes músculo-esqueléticas em um setor de montagem e embalagem de uma empresa multinacional da regiä da cidade de Säo Carlos - SP.Participaram deste estudo 50 trabalhadores com idades variando de 20 a 47 anos (média=30, 54; DP=7,51), sendo 18 homens e 32 mulheres. De acordo com os resultados, näo houve relaçäo entre os fatores ocupacionais analisados e as lesöes músculo-esqueléticas, com exceçäo da alta repetitividade nas atividades desenvolvidas