Nanostructured, Self-Assembling Peptide K5 Blocks TNF-α and PGE2 Production by Suppression of the AP-1/p38 Pathway

Nanostructured, self-assembling peptides hold promise for a variety of regenerative medical applications such as 3D cell culture systems, accelerated wound healing, and nerve repair. The aim of this study was to determine whether the self-assembling peptide K5 can be applied as a carrier of anti-inflammatory drugs. First, we examined whether the K5 self-assembling peptide itself can modulate various cellular inflammatory responses. We found that peptide K5 significantly suppressed the release of tumor-necrosis-factor- (TNF-) α and prostaglandin E2 (PGE2) from RAW264.7 cells and peritoneal macrophages stimulated by lipopolysaccharide (LPS). Similarly, there was inhibition of cyclooxygenase- (COX-) 2 mRNA expression assessed by real-time PCR, indicating that the inhibition is at the transcriptional level. In agreement with this finding, peptide K5 suppressed the translocation of the transcription factors activator protein (AP-1) and c-Jun and inhibited upstream inflammatory effectors including mitogen activated protein kinase (MAPK), p38, and mitogen-activated protein kinase kinase 3/6 (MKK 3/6). Whether this peptide exerts its effects via a transmembrane or cytoplasmic receptor is not clear. However, our data strongly suggest that the nanostructured, self-assembling peptide K5 may possess significant anti-inflammatory activity via suppression of the p38/AP-1 pathway

Perceived Stress and Frailty in Older Adults

Background Individuals with frailty are susceptible to adverse events. Although a psychological correlation with frailty has been observed, few studies have investigated the relationship between stress and frailty. This study examined the association between perceived stress and frailty in older adults. Methods This cross-sectional observational study included participants recruited between September 2021 and January 2022. The Korean version of the Perceived Stress Scale-10 was used to measure stress levels, while the frailty status was assessed using the Korean Frailty Index. Loneliness, depression, and satisfaction were measured using the UCLA Loneliness Scale, Centre for Epidemiological Studies Depression Scale, and Satisfaction with Life Scale, respectively. We used multinomial logistic regression to compare the variables between frail and robust participants. Results Among 862 study participants (mean age, 73.62 years; 65.5% women), the mean PSS-10 score was 15.26, 10.8% were frail, 22.4% were pre-frail, and 66.8% were robust. Perceived stress was significantly associated with pre-frailty (crude odds ratio [OR]=1.147; 95% confidence interval [CI], 1.093–1.204) and frailty (crude OR=1.417; 95% CI, 1.322–1.520). After adjusting for sociodemographic factors, we examined the associations between perceived stress and prefrailty (adjusted OR=1.140; 95% CI, 1.084–1.199) and frailty (adjusted OR=1.409; 95% CI, 1.308–1.518). After adjusting for all variables, including loneliness, depression, and satisfaction, perceived stress was significantly associated with frailty (adjusted OR=1.172; 95% CI, 1.071–1.283), however, insufficient statistical evidence was observed for pre-frailty (adjusted OR=1.022; 95% CI, 0.961–1.086). Conclusion Higher levels of perceived stress were associated with frailty in older adults. Stress management efforts may help improve frailty in this population

A modified method for inducing periodontitis in dogs using a silk-wire twisted ligature

This study was designed to assess the effectiveness of a modified silk ligature twisted with wire for inducing advanced periodontitis. Periodontitis was induced in five premolars and one molar of 20 healthy dogs over a 60-day period. The dogs were divided into four groups according to the ligature-inducing materials used: soft moistened food only, wire ligature (WL), silk ligature (SL) and twisted ligature with silk and wire (SWL). Periodontal indices were recorded, and dental radiographs were taken before and after 60 days of ligation. The ligatures were checked daily and the day the ligature fell out was noted. The period during which the ligatures were maintained was significantly shorter for the SL group compared to the SWL group (p < 0.05). Results of the clinical examination showed that almost all periodontal status parameters including the plaque index, gingival index, clinical attachment level, and bleeding on probing were significantly exacerbated in the SWL group compared to the other groups (p < 0.05). Radiographic evaluation demonstrated that alveolar bone levels were significantly lower in the SWL group than the other groups on day 60 (p < 0.05). These results suggested that experimental periodontitis induced by SWL could be an effective method for investigating periodontitis in canine models.OAIID:oai:osos.snu.ac.kr:snu2012-01/102/0000004182/3SEQ:3PERF_CD:SNU2012-01EVAL_ITEM_CD:102USER_ID:0000004182ADJUST_YN:YEMP_ID:A075461DEPT_CD:551CITE_RATE:1.161FILENAME:첨부된 내역이 없습니다.DEPT_NM:수의학과EMAIL:[email protected]_YN:YCONFIRM:

Association between phthalate exposure and lower handgrip strength in an elderly population: a repeated-measures study

Background Decreased muscle strength can lead to adverse health outcomes in the elderly. A potential association between phthalate exposure and muscle strength was suggested previously, but has not been investigated directly. We hypothesized that phthalate exposure is associated with lower handgrip strength and that the association is modified by the dietary omega-6 to omega-3 ratio. Methods We analyzed 1,228 participants (≥60 years of age) recruited in Seoul and Asan, Republic of Korea. The study participants were surveyed up to three times between 2012 and 2015. At every survey, we collected urine samples and measured handgrip strength twice for each hand. The associations between urine phthalate metabolite concentrations and handgrip strength were evaluated using linear mixed models. Based on dietary information from 391 individuals who participated in the first survey in Seoul, we evaluated the heterogeneity of the association for those with high and low omega-6 to omega-3 ratios, using 8.81 (the 75th quantile) as a cutoff value. Results Log-transformed creatinine-adjusted concentrations of mono-(2-ethyl-5-oxohexyl phthalate (MEOHP), mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), and mono-n-butyl phthalate (MnBP) were inversely associated with all measured handgrip strengths (β = −0.69 to −0.42, all p-values < 0.05). Associations between phthalate biomarkers and handgrip strength did not differ by sex. When the dietary subgroup was stratified by the omega-6 to omega-3 ratio, the associations were stronger among participants with high ratios. Conclusions We found inverse associations between phthalate biomarkers and handgrip strength in the elderly; this association was modified by the dietary omega-6 to omega-3 ratio

Association between hair mineral and age, BMI and nutrient intakes among Korean female adults

This study was performed to investigate the association between hair mineral levels and nutrient intakes, age, and BMI in female adults who visited a woman's clinic located in Seoul. Dietary intakes were assessed by food frequency questionnaire and mineral levels were measured in collected hairs, and the relationship between these was examined. The average daily nutrient intakes of subjects were compared to those of the KDRIs, and the energy intake status was fair. The average intake of calcium in women of 50 years and over was 91.35% of KDRIs and the potassium intake was greatly below the recommended levels in all age groups. In the average hair mineral contents in subjects, calcium and copper exceeded far more than the reference range while selenium was very low with 85.19% of subjects being lower than the reference value. In addition, the concentrations of sodium, potassium, iron, and manganese in the hair were below the reference ranges in over 15% of subjects. The concentrations of sodium, chromium, sulfur, and cadmium in the hair showed positive correlations (P < 0.05) with age, but the hair zinc level showed a negative correlation (P < 0.05) with age. The concentrations of sodium, potassium, chromium, and cadmium in the hair showed positive correlations (P < 0.05) with BMI. Some mineral levels in subjects of this study showed significant correlations with nutrient intakes, but it seems that the hair mineral content is not directly influenced by each mineral intake. As described above, some hair mineral levels in female adults deviated from the normal range, and it is considered that nutritional intervention to control the imbalance of mineral nutrition is required. Also, as some correlations were shown between hair mineral levels and age, BMI, and nutrient intakes, the possibility of utilizing hair mineral analysis for specific purposes in the future is suggested

A reduced dose of ribavirin does not influence the virologic response during pegylated interferon alpha-2b and ribavirin combination therapy in patients with genotype 1 chronic hepatitis C

Background/AimsWhen combined with pegylated interferon alpha-2b (Peg-IFN α-2b) for the treatment of genotype 1 chronic hepatitis C (CHC) in Korea, the current guideline for the initial ribavirin (RBV) dose is based on body weight. However, since the mean body weight is lower for Korean patients than for patients in Western countries, current guidelines might result in Korean patients being overdosed with RBV.MethodsWe retrospectively reviewed the medical records of patients with genotype 1 CHC who were treated with Peg-IFN α-2b and RBV combination therapy. We divided the patients into groups A (≥15 mg/kg/day, n=23) and B (<15 mg/kg/day, n=26), given that the standard dose is 15 mg/kg/day. The clinical course in terms of the virologic response, adverse events, and dose modification rate was compared between the two groups after therapy completion.ResultsThe early response rates (92.0% vs. 83.3%, P=0.634) and sustained virologic response rates (82.6% vs. 73.1%, P=0.506) did not differ significantly between the two groups. During the treatment period, the RBV dose reduction rate was significantly higher in group A than in group B (60.9% vs. 23.1%, P=0.01).ConclusionsRBV dose reduction is performed frequently when patients are treated according to the current Korean guidelines. Given that lowering the RBV dose did not appear to decrease the virologic response during therapy, reducing RBV doses below the current Korean guideline may be effective for treatment, especially in low-weight patients

Fulvestrant-induced expression of ErbB3 and ErbB4 receptors sensitizes oestrogen receptor-positive breast cancer cells to heregulin β1

Introduction We have previously reported that induction of epidermal growth factor receptor and ErbB2 in response to antihormonal agents may provide an early mechanism to allow breast cancer cells to evade the growth-inhibitory action of such therapies and ultimately drive resistant cell growth. More recently, the other two members of the ErbB receptor family, ErbB3 and ErbB4, have been implicated in antihormone resistance in breast cancer. In the present study, we have investigated whether induction of ErbB3 and/or ErbB4 may provide an alternative resistance mechanism to antihormonal action in a panel of four oestrogen receptor (ER)-positive breast cancer cell lines. Methods MCF-7, T47D, BT474 and MDAMB361 cell lines were exposed to fulvestrant (100 nM) for seven days, and effects on ErbB3/4 expression and signalling, as well as on cell growth, were assessed. Effects of heregulin β1 (HRGβ1) were also examined in the absence and presence of fulvestrant to determine the impact of ER blockade on the capacity of this ErbB3/4 ligand to promote signalling and cell proliferation. Results Fulvestrant potently reduced ER expression and transcriptional activity and significantly inhibited growth in MCF-7, T47D, BT474 and MDAMB361 cells. However, alongside this inhibitory activity, fulvestrant also consistently induced protein expression and activity of ErbB3 in MCF-7 and T47D cells and ErbB4 in BT474 and MDAMB361 cell lines. Consequently, fulvestrant treatment sensitised all cell lines to the actions of the ErbB3/4 ligand HRGβ1 with enhanced ErbB3/4-driven signalling activity, reexpression of cyclin D1 and significant increases in cell proliferation being observed when compared to untreated cells. Indeed, in T47D and MDAMB361 HRGβ1 was converted from a ligand having negligible or suppressive growth activity into one that potently promoted cell proliferation. Consequently, fulvestrant-mediated growth inhibition was completely overridden by HRGβ1 in all four cell lines. Conclusions These findings suggest that although antihormones such as fulvestrant may have potent acute growth-inhibitory activity in ER-positive breast cancer cells, their ability to induce and sensitise cells to growth factors may serve to reduce and ultimately limit their inhibitory activity

Pulmonary Tuberculosis and Delay in Anti-Tuberculous Treatment Are Important Risk Factors for Chronic Obstructive Pulmonary Disease

OBJECTIVE: Tuberculosis (TB) remains the leading cause of death among infectious diseases worldwide. It has been suggested as an important risk factor of chronic obstructive pulmonary disease (COPD), which is also a major cause of morbidity and mortality. This study investigated the impact of pulmonary TB and anti-TB treatment on the risk of developing COPD. DESIGN, SETTING, AND PARTICIPANTS: This cohort study used the National Health Insurance Database of Taiwan, particularly the Longitudinal Health Insurance Database 2005 to obtain 3,176 pulmonary TB cases and 15,880 control subjects matched in age, sex, and timing of entering the database. MAIN OUTCOME MEASURES: Hazard ratios of potential risk factors of COPD, especially pulmonary TB and anti-TB treatment. RESULTS: The mean age of pulmonary TB cases was 51.9±19.2. The interval between the initial study date and commencement of anti-TB treatment (delay in anti-TB treatment) was 75.8±65.4 days. Independent risk factors for developing COPD were age, male, low income, and history of pulmonary TB (hazard ratio 2.054 [1.768-2.387]), while diabetes mellitus was protective. The impact of TB persisted for six years after TB diagnosis and was significant in women and subjects aged >70 years. Among TB patients, delay in anti-TB treatment had a dose-response relationship with the risk of developing COPD. CONCLUSIONS: Some cases of COPD may be preventable by controlling the TB epidemic, early TB diagnosis, and prompt initiation of appropriate anti-TB treatment. Follow-up care and early intervention for COPD may be necessary for treated TB patients

Minor intron splicing is critical for survival of lethal prostate cancer.

The evolutionarily conserved minor spliceosome (MiS) is required for protein expression of ∼714 minor intron-containing genes (MIGs) crucial for cell-cycle regulation, DNA repair, and MAP-kinase signaling. We explored the role of MIGs and MiS in cancer, taking prostate cancer (PCa) as an exemplar. Both androgen receptor signaling and elevated levels of U6atac, a MiS small nuclear RNA, regulate MiS activity, which is highest in advanced metastatic PCa. siU6atac-mediated MiS inhibition in PCa in vitro model systems resulted in aberrant minor intron splicing leading to cell-cycle G1 arrest. Small interfering RNA knocking down U6atac was ∼50% more efficient in lowering tumor burden in models of advanced therapy-resistant PCa compared with standard antiandrogen therapy. In lethal PCa, siU6atac disrupted the splicing of a crucial lineage dependency factor, the RE1-silencing factor (REST). Taken together, we have nominated MiS as a vulnerability for lethal PCa and potentially other cancers

Dental management considerations for the patient with an acquired coagulopathy. Part 1: Coagulopathies from systemic disease

Current teaching suggests that many patients are at risk for prolonged bleeding during and following invasive dental procedures, due to an acquired coagulopathy from systemic disease and/or from medications. However, treatment standards for these patients often are the result of long-standing dogma with little or no scientific basis. The medical history is critical for the identification of patients potentially at risk for prolonged bleeding from dental treatment. Some time-honoured laboratory tests have little or no use in community dental practice. Loss of functioning hepatic, renal, or bone marrow tissue predisposes to acquired coagulopathies through different mechanisms, but the relationship to oral haemostasis is poorly understood. Given the lack of established, science-based standards, proper dental management requires an understanding of certain principles of pathophysiology for these medical conditions and a few standard laboratory tests. Making changes in anticoagulant drug regimens are often unwarranted and/or expensive, and can put patients at far greater risk for morbidity and mortality than the unlikely outcome of postoperative bleeding. It should be recognised that prolonged bleeding is a rare event following invasive dental procedures, and therefore the vast majority of patients with suspected acquired coagulopathies are best managed in the community practice setting