Inhibitory effects of lycopene on HMGB1-mediated pro-inflammatory responses in both cellular and animal models

High mobility group box 1 (HMGB1) mediates proinflammatory responses in inflammatory diseases. Lycopene found in tomatoes and tomato products has anti-oxidant, anti-cancer and antiinflammatory effects. The potential anti-inflammatory roles of lycopene in HMGB1-mediated proinflammatory responses in both primary human umbilical vein endothelial cells (HUVECs) and animal were investigated. The anti-inflammatory effects of lycopene were determined including permeability, monocyte adhesion and migration, and activation of proinflammatory proteins and HMGB1 receptors on HMGB1 activated HUVECs. In the in vivo model, the anti-inflammatory effect of lycopene was assessed by monitoring vascular permeability and migration of leukocytes to the peritoneal cavity of mice injected with lycopene. Lycopene inhibited lipopolysaccharide (LPS)-mediated release of HMGB1, expression of HMGB1-mediated tumor necrosis factor (TNF)-secretory phospholipase A2 (sPLA2)-IIA, and HMGB1-mediated pro-inflammatory signaling responses in endothelial cells. It did this through down-regulation of cell surface expression of cell adhesion molecules (CAMs), HMGB1 receptors, toll-like receptor (TLR)-2, and -4, and receptors for advanced glycation end products (RAGE). These findings suggest that lycopene promotes barrier integrity, inhibits monocyte adhesion and migration to HMGB1 activating HUVECs by blocking activation of proinflammatory cytokines and expression of CAMs and HMGB1 receptors, thereby showing its usefulness as a therapy for vascular inflammatory diseases.     

The bark of Betula platyphylla var. japonica inhibits the development of atopic dermatitis-like skin lesions in NC/Nga mice

The bark of Betula platyphylla Sukat. var. japonica Hara (Asian White Birch, AWB) is one of the herbs used in Eastern countries for the treatment of various inflammatory diseases including atopic dermatitis (AD). The present study was performed to examine if and how the bark of AWB inhibits the development of AD-like skin lesions in NC/Nga mice induced by repeated application of picryl chloride (PC). With this aim, we examined the skin symptom severity, itching behavior, serum immunoglobulin (Ig) E level and mRNA expression of cytokines at iliac and cervical lymph nodes in the mice. Oral administration of AWB extracts (25, 100 and 250 mg/kg) to the PC-treated mice inhibited the development of AD-like skin lesions as exemplified by a significant decrease in the total skin severity scores, itching behavior and a decrease in hypertrophy and infiltration of inflammatory cells into dermis. The serum IgE level was also significantly reduced by AWB extract. In the RT-PCR results, the expression of interleukin-4 mRNA was reduced by AWB extract, whereas the expression of interferon-gamma mRNA was not changed. These results suggest that AWB inhibits the development of AD-like skin lesions in NC/Nga mice through the suppression of the T-helper 2 cell response.     

Clinical analysis of synchronous primary neoplasms of the female reproductive tract

OBJECTIVES: In this study, a histopathologic review of synchronous primary neoplasms including gynecologic malignancies is presented, and the possible correlation among discrete tumor subsets, natural history, and survival is evaluated. METHODS: Between the years 2000 and 2005, 20 patients suffering from synchronous primary cancers of gynecologic malignancy were identified. Clinical and pathologic information was obtained from medical records. Kaplan-Meier survival analyses were conducted. RESULTS: Patients with synchronous primary malignancies constituted 0.63% of all genital malignancies. The most frequently observed synchronous neoplasm was ovarian cancer coexistent with endometrial cancer (40%). The mean age of patients suffering from synchronous ovarian and endometrial cancer was 45.2 years. All patients with synchronous primary genital malignancies underwent hysterectomy with bilateral salpingo-oophorectomy and/or adjuvant therapy. The mean duration of survival was 57 months (S.E.: 10.0; 95% confidence interval: 37-77). CONCLUSION: Patients suffering from primary genital malignancies are sometimes co-afflicted with other primary cancers. Synchronous ovarian and endometrial cancer constitutes the most common of these cases, and is detected at a relatively early age, with generally favorable prognoses.     

Management of high-risk hydatidiform mole and persistent gestational trophoblastic neoplasia: the Korean experience

OBJECTIVE: To test the efficacy of a new scoring system to differentiate high-risk hydatidiform mole (H-mole) and initiate early selective postmolar chemotherapy. STUDY DESIGN: According to Kim's scoring system, 262 patients were identified as high-risk H-mole patients. Fifty (19.1%) received early chemotherapy, and the rest constituted the control group. Salvage therapy with etoposide, methotrexate, actinomycin D/etoposide, cisplatin (EMA/EP) and taxol, cisplatin/taxol, etoposide (TP/TE) was applied in 21 cases of ultra-high-risk GTT. RESULTS: None of the 50 cases in the early chemotherapy group progressed to persistent GTT. However, 58.9% in the control group developed GTT with 8.0% drug resistance. Of those receiving salvage therapy in the 21 ultra-high-risk GTT cases resistant to EMA/CO, 10 of 14 (71%) receiving EMA/EP and 4 of 7 (57.1%) receiving TP/TE achieved remission. CONCLUSION: Early postmolar chemotherapy for high-risk H-mole is effective in preventing progression to persistent GTT and treatment failure. Ultra-high-risk GTT should be approached with multimodal treatment, including EMA/EP and TP/TE regimens.     

Increased Omega-3 Fatty Acid Intake Is Associated with Low Grip Strength in Elderly Korean Females

Omega-3 fatty acids, such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), have anti-inflammatory properties and have recently been considered essential factors for maintaining muscle health. This study aimed to investigate the relationship between omega-3 fatty acid intakes and sarcopenia by assessing grip strength in elderly Koreans who are at risk of sarcopenia. This study was conducted on 5529 individuals (2449 males and 3080 females) aged ≥65 years from the raw data of the Korea National Health and Nutrition Examination Survey 2015–2019. In this study, we analyzed the association between EPA and DHA intake, calculated from a 24-h recall method data, and grip strength, a diagnostic criterion for sarcopenia. The cut-off values for low grip strength were <26 kg for males and <18 kg for females, which were set for the Asian population. The results indicated that elderly females consuming EPA and DHA below the adequate intake (AI) had significantly lower grip strength (p < 0.0001) and, had a higher percentage contribution from carbohydrates, but a significantly lower percentage contribution from protein (p < 0.0001), compared to elderly females consuming EPA and DHA at or above the AI. In addition, after adjusting for confounding factors, the odds of low grip strength were 0.777 times lower among elderly females consuming EPA and DHA at or above the AI than those consuming EPA and DHA below the AI (95% confidence interval: 0.616–0.979, p = 0.0322). These results suggest that sufficient intake of EPA and DHA is pivotal to mitigate a reduction in grip strength and to improve the quality of nutrient intake among elderly females.     

Sodium Glucose Cotransporter-2 Inhibitors as an Add-on Therapy to Metformin Plus Dipeptidyl Peptidase-4 Inhibitor in Patients with Type 2 Diabetes

PurposeTo date, no study has compared the effects of adding sodium glucose cotransporter-2 (SGLT-2) inhibitors to the combination of metformin plus dipeptidyl peptidase-4 (DPP-4) inhibitors to the effects of adding other conventional anti-diabetic drugs (ADDs) to the dual therapy. We aimed to compare the effect of adding SGLT-2 inhibitors with that of adding sulfonylurea (SU) in type 2 diabetes (T2D) patients inadequately controlled with metformin plus DPP-4 inhibitors.Materials and MethodsThis study was designed to evaluate the non-inferiority of SGLT-2 inhibitor to SU as an add-on therapy to the dual combination of metformin plus DPP-4 inhibitors. A total of 292 T2D patients who started SU or SGLT-2 inhibitors as an add-on therapy to metformin plus DPP-4 inhibitors due to uncontrolled hyperglycemia, defined as glycated hemoglobin (HbA1c) ≥7%, were recruited. After propensity score matching, 90 pairs of patients remained, and 12-week changes in HbA1c levels were reviewed to assess glycemic effectiveness. Data from these patients were analyzed retrospectively.ResultsAfter 12 weeks of triple therapy, both groups showed significant changes in HbA1c levels, with a mean of -0.9% in each group. The inter-group difference was 0.01% [95% confidence interval (CI): -0.26–0.27], and the upper limit of the 95% CI was within the limit for non-inferiority (0.40%). There were no inter-group differences in the changes of liver enzyme levels and kidney function.ConclusionAdding SGLT-2 inhibitors is not inferior to adding SU as a third-line ADD to metformin plus DPP-4 inhibitor combination therapy.     

A Retrospective National Study on Colonization Rate and Antimicrobial Susceptibility of Streptococcus agalactiae in Pregnant Korean Women, 2018–2020

PurposeThe prevalence of Group B Streptococcus (GBS) colonization in pregnant Korean women is increasing; however, nationwide studies are lacking. Therefore, we aimed to analyze regional colonization rates and antimicrobial susceptibility for GBS in pregnant Korean women through a nationwide survey.Materials and MethodsFrom January 2018 to December 2020, data from the Seoul Clinical Laboratories on vaginal swab cultures were retrospectively analyzed to detect maternal GBS carriers. Each swab specimen was inoculated onto a 5% blood agar plate and incubated at 35℃–37℃ in a 5% CO₂ incubator for 24 h. GBS isolates were identified using a Microflex MALDI Biotyper. Antimicrobial susceptibility tests were performed using the Vitek 2 automated system.ResultsThe overall nationwide GBS colonization rate in pregnant Korean women was found to be 10.6% (3578/33721). The maternal GBS colonization rates ranged from 10.5%–10.8% over the 3-year study period. The GBS colonization rates by province, in descending order, were as follows: Jeolla-do, 13.2%; Gangwon-do, 12.0%; Chungcheong-do, 11.8%; Gyeonggi-do, 11.3%; Seoul, 10.2%; and Gyeongsang-do, 9.6%. During the study period, the resistance rates against chloramphenicol, levofloxacin, clindamycin, erythromycin, and tetracycline were 2.6%–2.7%, 18.2%–19.6%, 33.4%–35.7%, 35.6%–36.8%, and 50.5%–53.3%, respectively.ConclusionIn pregnant Korean women, GBS colonization rates were in the range of 9.6%–13.2%, with Gyeongsang-do being the lowest and Jeolla-do the highest. The resistance rate against clindamycin was high (33.4%–35.7%). GBS colonization rates during pregnancy should be studied nationwide according to the Centers for Disease Control and Prevention-recommended guidelines with periodic antimicrobial resistance monitoring.     

Surgical Complications and the Risk Factors of Laparoscopy-Assisted Distal Gastrectomy in Early Gastric Cancer

Background Information on surgical complications of laparoscopy-assisted distal gastrectomy (LADG) and their risk factors is limited in the literature despite increasing popularity of this procedure. This study was performed to identify the surgical complications and their associated risk factors of LADG in early gastric cancer. Methods LADG was performed in 347 gastric cancer patients from January 2002 to December 2006 at the Korean National Cancer Center by four surgeons with ample experience of open gastric surgery before LADG. LADG indications for cases of gastric cancer at our institution are preoperatively diagnosed cT1N0 or cT1N1, except in cases with an absolute indication for endoscopic resection. Lymph node dissection of more than D1 + β was performed in all patients. Intraoperative and postoperative complications were reviewed and their risk factors were retrospectively analyzed by prospective database information. Results Forty complications occurred in 34 patients (9.8%), but there was no mortality. Intraoperative complications occurred in nine patients (2.6%), and open conversion was performed in eight (2.3%) of these patients. Early and late postoperative complications occurred in 21 (6.1%) and 10 (2.9%) patients, respectively. The most serious complication was vascular injury resulting in bleeding or organ ischemia, which occurred in seven patients. Degree of lymph node dissection and surgical inexperience were found to be risk factors of surgical complication (P = .023, odds ratio 2.832, 95% confidence interval 1.155–6.946 vs. P = .028, odds ratio 2.975, 95% confidence interval 1.127–7.854). Conclusions Lymph node dissection during LADG should be performed cautiously to prevent surgical complications like vascular injuries, especially during the surgeon’s early learning period.     

The Effect of Campaign-Generated Interpersonal Communication on Campaign-Targeted Health Outcomes: A Meta-Analysis

This study examined the effect of mass media campaign-generated conversations on campaign-targeted health outcomes, via a systematic meta-analysis of 28 studies (including 124 sub-studies and a total of 138,898 participants). The study also conducted a series of moderation analyses to examine the conditions under which interpersonal communication has larger effects on bringing about the desired outcomes. The findings of this meta-analysis indicate that campaign-generated conversations have a positive effect on inducing campaign-targeted outcomes (OR = 1.28) and show that this effect is moderated by health topic addressed by the campaign, the type of outcome being targeted by the campaign, and with whom people converse, along with several other campaign-relevant and study-relevant variables. The implications of these findings for future research are discussed.     

Effects of Arg–Gly–Asp-modified elastin-like polypeptide on pseudoislet formation via up-regulation of cell adhesion molecules and extracellular matrix proteins

Extracellular matrix (ECM) plays an important role in controlling the β-cell morphology, survival and insulin secretary functions. An RGD-modified elastin-like polypeptide (RGD-ELP), TGPG[VGRGD(VGVPG)₆]₂₀WPC, has been reported previously as a bioactive matrix. In this study, to investigate whether RGD-ELP affects β-cell growth characteristics and insulin secretion, β-TC6 cells were cultured on the RGD-ELP coatings prepared via thermally induced phase transition. On RGD-ELP, β-TC6 cells clustered into an islet-like architecture with high cell viability. Throughout 7 days’ culture, the proliferation rate of the cells within a pseudoislet was similar to that of monolayer culture. Under high glucose (25 mM), β-TC6 pseudoislets showed up-regulated insulin gene expression and exhibited glucose-stimulated insulin secretion. Importantly, the mRNA and protein abundances of cell adhesion molecules (CAM) E-cadherin and connexin-36 were much higher in pseudoislets than in monolayer cells. The siRNA-mediated inhibition of E-cadherin or connexin-36 expression severely limited pseudoislet formation. In addition, the mRNA levels of collagen types I and IV, fibronectin and laminin were significantly elevated in pseudoislets. The results suggest that RGD-ELP promotes pseudoislet formation via up-regulation of the CAM and ECM components. The functional roles of RGD-ELP are discussed in respect of its molecular composition.