Rutin and Gallic Acid Regulates Mitochondrial Functions via the SIRT1 Pathway in C2C12 Myotubes.

Mitochondria are highly dynamic organelles, balancing synthesis and degradation in response to increases in mitochondrial turnover (i.e., biogenesis, fusion, fission, and mitophagy) and function. The aim of this study was to investigate the role of polyphenols in the regulation of mitochondrial functions and dynamics in C2C12 myotubes and their molecular mechanisms. Our results indicate that gallic acid and rutin are the most potential polyphenol compounds in response to 15 phenolic acids and 5 flavonoids. Gallic acid and rutin were associated with a significantly greater mitochondrial DNA (cytochrome b and COX-II), mitochondrial enzymatic activities (including citrate synthase and cytochrome c oxidase), and intracellular ATP levels in C2C12 myotubes. Moreover, gallic acid and rutin significantly increased the gene expressions of mitochondrial turnover in C2C12 myotubes. Our findings indicated that gallic acid and rutin may have a beneficial effect on mitochondrial dynamics via regulation of the SIRT1-associated pathway in C2C12 myotubes.

Treatment of chronic hepatitis C regiments containing with recombinant interferon in patients with sustained virological response predicts risk of hepatocellular carcinoma: A meta-analysis.

Given that evidence supporting chronic hepatitis C (CHC) infection developed chance for hepatocellular carcinoma (HCC) following antiviral agents therapy is controversial. We conducted a meta-analysis to examine the risk.We evaluated 20 retrospective and prospective cohort studies published up to 31 December 2017 which investigated the association between sustained virological response (SVR) and incidence of HCC patients treated with monotherapy interferon (IFN) or IFN plus ribavirin (RBV) therapy. The primary outcome of the study was the cumulative incidence of HCC. Odds ratio (OR) was used to evaluate the index of effect size for the association between SVR and treatment with IFN alone or IFN/RBV in CHC patients.SVR patients demonstrated a lower incidence of HCC compared to non-SVR patients. Non-SVR patients had greater odds of HCC incidence compared to SVR patients in the treatment of IFN plus RBV (pooled OR = 7.405, 95% CI = 4.689 to 11.694, P < .001). Non-SVR patients had greater odds of HCC incidence compared to SVR patients in the treatment of IFN monotherapy (pooled OR = 4.135, 95% CI = 3.009 to 5.682, P < .001). Lack of SVR to IFN therapy was significantly associated with greater risk of HCC incidence (pooled OR = 5.035, 95% CI = 3.915 to 6.474, P < .001).SVR could be as a predictor of HCC in CHC patients treated with IFN or IFN plus RBV, and have important implications during HCC screening, whereby patients who fail to achieve SVR need to be screened more rigorously.

E3 ligase carboxyl-terminus of Hsp70-interacting protein (CHIP) suppresses fibrotic properties in oral mucosa.

BACKGROUND/PURPOSE: Oral submucous fibrosis (OSF) represents a precancerous lesion of oral mucosa that may progress into oral cancer and its major etiological factor is areca nut chewing. Carboxyl-terminus of Hsp70-interacting protein (CHIP) functions as an ubiquitin E3 ligase and is associated with fibrosis diseases. In the current study, we sought to investigate whether CHIP participated in the areca nut-mediated OSF development. METHODS: The mRNA expression of CHIP in arecoline-stimulated buccal mucosal fibroblasts (BMFs) and OSF tissues was determined by qRT-PCR. Collagen gel contraction, migration and invasion assays were carried out to evaluate the myofibroblast activation. The protein expression levels of α-SMA and transglutaminase 2 (TGM2) were assessed by Western blot. RESULTS: The expression level of CHIP was reduced in BMFs following arecoline treatment in a dose-dependent manner, which was consistent with the observation of lower CHIP expression in OSF specimen compared to the normal counterparts. Ectopic expression of CHIP mitigated the myofibroblast activities, including elevated collagen gel contractility and cell motility. In addition, we showed that overexpression of CHIP downregulated the α-SMA and TGM-2 expression, which may lead to less fibrosis alteration. CONCLUSION: CHIP may not only function as a key regulator of protein quality control but also a critical deciding factor to oral fibrogenesis. Our findings suggested that CHIP possesses the anti-fibrotic effect, which may be mediated by TGM2 regulation. Restoration of CHIP could be a therapeutic direction to help OSF patients.

Maintenance interferon therapy in chronic hepatitis C patients who failed initial antiviral therapy: A meta-analysis.

OBJECTIVES: To evaluate the effect of pegylated interferon maintenance therapy in patients with chronic hepatitis C who failed initial antiviral therapy. METHODS: This is a meta-analysis of 6 randomized controlled trials that met the eligibility criteria. In all, 2438 chronic hepatitis C patients who failed to achieve sustained virologic response after initial treatment with pegylated interferon and ribavirin (antiviral therapy nonresponders or relapsers) were enrolled; 1237 patients received maintenance therapy (Maintenance group) and 1201 received no treatment (Observation group). RESULTS: The pooled analyses found that patients in the Maintenance group had a significantly higher rate of normal alanine aminotransferase than did patients in the Observation group (pooled odds ratio [OR] 4.436, 95% confidence interval [CI] 1.225-16.064, P = .023), but there was no significant difference between the 2 groups in the incidence of hepatocellular carcinoma (pooled OR 0.872, 95% CI 0.501-1.519, P = .630), or the mortality rate (pooled OR 1.564, 95% CI 0.807-3.032, P = .185). CONCLUSIONS: Interferon-based maintenance therapy in patients with chronic hepatitis C who failed initial antiviral therapy improved liver inflammation as indicated by blood chemistry (alanine aminotransferase).

Effects of Long Noncoding RNA H19 Polymorphisms on Urothelial Cell Carcinoma Development.

Urothelial cell carcinoma (UCC) is one of the major malignancies of the genitourinary tract, and it is induced by carcinogenic epidemiological risk factors. H19 is one of the most crucial long noncoding RNAs (lncRNAs) and is involved in various types of bladder cancer. In this study, we examined H19 single-nucleotide polymorphisms (SNPs) to investigate UCC susceptibility and clinicopathological characteristics. Using real-time polymerase chain reaction, we analyzed five SNPs of H19 in 431 UCC patients and 431 controls without cancer. The results showed that patients with UCC carrying the H19 rs217727 CT + TT and rs2107425 CT + TT genetic variants had a high risk of developing muscle invasive tumors (pT2-T4) (p = 0.030; p = 0.025, respectively). With a median follow up of 39 months, CT+TT polymorphisms of rs2107425 were associated with worse disease-specific survival (adjusted hard ratio (AHR) = 2.043, 95% confidence interval (CI) = 1.029-4.059) in UCC patients aged older than 65 years. In conclusion, our results indicate that patients with UCC carrying the H19 rs217727 CT + TT and rs2107425 CT + TT genetic variants have a high risk of developing muscle invasive tumors. Thus, H19 polymorphisms may be applied as a marker or therapeutic target in UCC treatment.

Human papillomavirus prevalence and behavioral risk factors among HIV-infected and HIV-uninfected men who have sex with men in Taiwan.

Human papillomavirus (HPV) infection is associated with cancer and can be prevented through vaccination. Few studies from Taiwan have reported on HPV infection among human immunodeficiency virus (HIV)-infected subjects. The aim of this study was to examine the prevalence of HPV infection among men who have sex with men (MSM) with and without HIV infection in Taiwan, and explore the behavioral risk factors thereof.We conducted a cross-sectional study in Taiwan during 2013 to 2016 to collect data on MSM aged 20 years or older. We used a questionnaire in a face-to-face interview, and subsequently collected oral, anal, and genital specimens from HIV-infected and HIV-uninfected subjects. Multivariate analysis was performed to predict factors associated with high-risk HPV (HR-HPV) positivity.Overall, 279 subjects, including 166 (59.5%) HIV-uninfected and 113 (40.5%) HIV-infected men were enrolled. Compared to HPV-negative subjects, HPV-positive subjects had significantly higher rates of receptive anal sex (91.3% vs 75.6%), substance use (22.6% vs 11%), history of sexually transmitted infections (75.7% vs 38.4%), anogenital or oral warts (39.1% vs 6.72%), syphilis (32.2% vs 11.6%), and HIV infection (69.6% vs 20.1%). We detected 489 HPV deoxyribonucleic acid (DNA) types (through 379 viable specimens), of which 43.6%, 5.7%, 56.4%, and 10.4% were HR-HPV type, HPV type 16, low-risk HPV types, and HPV type 6, respectively. In multivariate analysis, HIV-infected subjects had a significantly higher prevalence of HR-HPV infection (adjusted odds ratio, 5.80; 95% confidence interval, 2.57-13.11), compared to HIV-uninfected subjects.These results suggest that the prevalence of HPV infection was high among HIV-infected MSM. Additionally, anal HPV infection was observed to be common among both HIV-infected and HIV-uninfected MSM in Taiwan. The prevalence of oral and genital HPV infection, HR-HPV DNA types, and multiple HPV types was higher in HIV-infected subjects than in HIV-uninfected subjects. As only 35% of subjects practiced safe sex, we recommend routine HPV vaccination with 4-valent HPV or 9-valent HPV vaccines for both MSM, and HIV-infected subjects.

Complicated skin and soft tissue infection with Mycobacterium fortuitum following excision of a sebaceous cyst in Taiwan.

Mycobacterium fortuitum group (M. fortuitum), also known as rapidly growing Mycobacteria, can cause pyogenic infections in human beings, most commonly in immunocompromised patients. Herein, we present a 40-year-old immunocompetent male patient who underwent planned excision of a sebaceous cyst in the abdominal wall. He suffered from tender erythematous lesions with purulent discharge around the healing wound that developed 2 weeks after surgery. Gram stain, bacterial and fungal culture results of the wound were negative. A diagnosis of non-tuberculous mycobacteria was made from a wound culture from the area of operative debridement, which was subsequently confirmed to be M. fortuitum group using PCR-restriction fragment length polymorphism analysis of the hsp65 gene. The patient received 4 weeks of parenteral imipenem/cilastatin 500 mg every 6 hours and amikacin 500 mg every 12 hours, plus oral clarithromycin 500 mg twice daily, and the wound recovered completely. He was discharged and followed up regularly at our outpatient clinic, and continued taking oral ciprofloxacin and clarithromycin 500 mg twice daily for 6 months. This case highlights the importance of strict aseptic precautions even during minor procedures, and also the characteristics of M. fortuitum infections in immunocompetent patients, which usually develop as localized postsurgical wound infections. We also share our experience in successfully treating a M. fortuitum complicated skin and soft tissue infection.

Association of single-nucleotide polymorphisms of high-mobility group box 1 with susceptibility and clinicopathological characteristics of uterine cervical neoplasia in Taiwanese women.

To date, no study associated the genetic polymorphisms of high-mobility group box 1 protein (HMGB1) with the development of uterine cervical cancer. We therefore conducted this study to investigate the associations of HMGB1 single-nucleotide polymorphisms (SNPs) with cervical carcinogenesis and clinicopathological characteristics of cancer patients. Five hundred two women, including 112 with invasive cancer, 85 with precancerous lesions of the uterine cervix, and 305 normal controls, were consecutively enrolled into this study. Analysis of HMGB1 SNPs was done by real-time polymerase chain reaction and genotyping. Our results found that the risk of susceptibility to cervical invasive cancer was 1.85 (95 % CI 1.12-3.04; p = 0.016) in women with TC and 1.99 (95 % CI 1.24-3.23; p = 0.005) in women with TC/CC after adjusting for age, using TT as a comparison reference in HMGB1 SNP rs1412125. In rs2249825, the increased risk was also seen for the development of cervical invasive cancer in women with CG [adjusted odds ratio (AOR) 2.04, 95 % CI 1.22-3.40; p = 0.006] or CG/GG (AOR 2.02, 95 % CI 1.22-3.32; p = 0.006) using CC as a comparison reference. An additional integrated in silico analysis confirmed that rs2249825 creates a binding site for v-Myb, which may affect HMGB1 expression. In conclusion, Taiwanese women with TC or TC/CC in HMGB1 SNP rs1412125 as well as CG or CG/GG in rs2249825 were susceptible to the development of cervical invasive cancer.

Drug Prescribing in the Elderly Receiving Home Care.

BACKGROUND: To compare the prevalence of potentially inappropriate medications (PIMs) using the 2012 and 2003 Beers Criteria in frail older patients receiving home health care services (HHS), and to explore the correlates of PIMs based on the 2012 Beers criteria. MATERIALS AND METHODS: A total of 145 older patients (mean age, 80.9 ± 7.6 years) with Barthel scale ≤ 60 receiving regular HHS from a university hospital between January 2013 and June 2013 were retrospectively enrolled. The 2003 and 2012 Beers criteria were used separately to detect PIMs. Logistic regressions, receiver-operating-characteristic curve analyses and number needed to harm were used, where appropriate. RESULTS: The 2012 Beers Criteria identified more PIM cases than did the 2003 Beers Criteria (66.9% versus 55.9%, P < 0.05). Multivariate analysis revealed that PIM identified by the 2012 Beers Criteria was associated with an increased number of medications prescribed (P = 0.019) and the presence of psychiatric diseases (P = 0.001). Moreover, the area under the receiver-operating-characteristic curve for the number of drugs to predict the risk of PIM was 0.674 (P < 0.001) with the optimal cutoff value of 6 medications. After adjusting for age, sex, Charlson comorbidity index and psychiatric disorders, patients taking ≥6 drugs (adjusted odds ratio, 2.33; adjusted number needed to harm, 3.93; P < 0.05) had a significantly higher risk for PIM than those taking <6 drugs. CONCLUSIONS: Our data showed that the 2012 Beers Criteria was more sensitive in detecting PIMs than the 2003 Beers Criteria. Furthermore, frail older patients receiving HHS with polymedication and with psychiatric illnesses had higher risk of PIM when using the 2012 criteria. The number of medications prescribed could be a useful index for risk stratification, and at the same time help physicians to be aware of the high risk for PIM when prescribing 6 or more drugs to frail older adults during in-home visits.

Long-chain polyunsaturated fatty acids amend palmitate-induced inflammation and insulin resistance in mouse C2C12 myotubes.

Intramuscular lipid accumulation results in inflammation, which is correlated with impaired insulin action in the skeletal muscle, an important organ for glucose uptake in the body. In this study, we explored the effects of docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), arachidonic acid (AA), and long-chain polyunsaturated fatty acids (PUFAs) on palmitic acid (PA)-induced inflammatory responses and insulin resistance in C2C12 myotubes. The mRNA expression of the pro-inflammatory cytokines interleukin-6 and tumor necrosis factor-α in PA-treated myotubes was suppressed by these three test long-chain PUFAs. Moreover, the addition of long-chain PUFAs decreased PA-induced insulin resistance as evidenced by increases in phosphorylated AKT and glucose uptake. In PA-treated myotubes, long-chain PUFAs improved glucose transporter 4 expression, basal glucose uptake without insulin, and the AMP-activated protein kinase pathway. Of note, the long-chain PUFAs obstructed the effects of PA on the activation of extracellular-signal-regulated kinase and protein kinase C-θ as well as nuclear factor-κB (NF-κB) and activator protein-1. The inhibitory effect of AA but not of DHA and EPA on PA-induced inflammation and impaired insulin action was cancelled in C2C12 myotubes transfected with a constitutively active mutant IκB kinase-ß plasmid. These data suggest that long-chain PUFAs may be useful in the management of PA-induced inflammation and insulin resistance in myotubes. In addition to the NF-κB pathway, other mechanisms are involved in the health benefits of DHA and EPA in PA-treated myotubes.

Chimeric groin free flaps: Design and clinical application.

BACKGROUND: Reconstruction of composite extremity defects or through-and-through oral defects remains challenging for surgeons. Chimeric flaps are ideal for repairing these lesions. In this article, we report the design of various chimeric groin free flaps for the reconstruction of both complex oral and extremity defects in 18 patients. METHODS: Between 2010 and 2014, 18 patients with composite tissue defect or two defects in the extremities or head and neck region, underwent reconstruction with cutaneous-cutaneous, musculo-cutaneous, or osteo-cutaneous chimeric groin free flaps. The size and pedicles length of the chimeric groin flaps based on the superficial circumflex iliac artery (SCIA) were tailored to the lesions. Patient-reported post-operative outcomes at the out-patient department were evaluated. RESULTS: The types of chimeric groin free flaps included cutaneous-cutaneous (n = 12), musculo-cutaneous (n = 1), and osteo-cutaneous (n = 5) flaps. Three to four SCIA branches (mean: 3.33) could be used for flap design. The cutaneous flap size ranged from 1.5 cm × 6 cm to 11 cm × 30 cm, and the bone flap size ranged from 1 cm × 1.5 cm to 2.5 cm × 6 cm. All flaps survived, and no significant complications developed at recipient or donor sites. Functional recovery after reconstruction was satisfactory in most patients after a mean of 17.27 months (ranging 2-42 months) of follow-up. CONCLUSION: The innovative flap technique presented herein has advantages including greater reliability, as well as the ability to tailor the dimensions and flap paddles to specific lesions and reconstruct two defects or one composite defect using only one (chimeric) flap.

Potentially Inappropriate Prescribing in Disabled Older Patients with Chronic Diseases: A Screening Tool of Older Persons' Potentially Inappropriate Prescriptions versus Beers 2012 Criteria.

OBJECTIVE: To evaluate the prescription of potentially inappropriate medications (PIM), using the Screening Tool of Older Persons' potentially inappropriate Prescriptions (STOPP) and Beers criteria, to disabled older people. SUBJECTS AND METHODS: One hundred and forty-one patients aged ≥65 years with Barthel scale scores ≤60 and a regular intake of medication for chronic diseases at Chung Shan Medical University Hospital from July to December 2012 were included, and their medical records were reviewed. Comprehensive patient information was extracted from the patients' medical notes. The STOPP and Beers 2012 criteria were used separately to identify PIM, and logistic regression analyses were performed to identify risk factors for PIM. The optimal cutoff for the number of medications prescribed for predicting PIM was estimated using the Youden index. RESULTS: Of the 141 patients, 94 (66.7%) and 94 (66.7%) had at least one PIM identified by the STOPP and Beers criteria, respectively. In multivariate analysis, PIM identified by the Beers criteria were associated with the prescription of multiple medications (p = 0.013) and the presence of psychiatric diseases (p < 0.001), whereas PIM identified by the STOPP criteria were only associated with the prescription of multiple medications (p = 0.008). The optimal cutoff for the number of medications prescribed for predicting PIM by using the STOPP or Beers criteria was 6. After adjustment for covariates, patients prescribed ≥6 medications had a significantly higher risk of PIM, identified using the STOPP or Beers criteria, compared to patients prescribed <6 medications (both p < 0.05). CONCLUSION: This study revealed a high frequency of PIM in disabled older patients with chronic diseases, particularly those prescribed ≥6 medications.

Pulmonary Mucormycosis in a Patient with Systemic Lupus Erythematosus: A Diagnostic and Treatment Challenge.

Pulmonary mucormycosis is commonly encountered in patients with diabetic ketoacidosis, hematologic malignancies, neutropenia, organ or hematopoietic stem cell transplantation, and malignancy, but it rarely occurs in high-risk patients with systemic lupus erythematosus (SLE). We present the case of a 40-year-old SLE female with fulminant pneumonia after remission of nephritis treated with rituximab, who developed severe pulmonary mucormycosis that led to her rapid death from acute respiratory failure and acute respiratory distress syndrome. Pulmonary mucormycosis has a high mortality rate. However, with early diagnosis and antifungal therapy with lipid formulation-liposomal amphotericin B and surgical removal of the infected area, the outcome can be improved.

Freestyle groin flaps: the real axial flap design and clinical application.

BACKGROUND: The groin flap represents a milestone in the history of flap development, since it was the first successful free cutaneous flap. Once widely used, it is currently less popular owing to the variations in vascular anatomy and the small, short pedicle. To enhance the clinical applications of the groin flap, its merits need to be promoted and its faults improved, including making some useful innovations. METHODS: From February 2010 to February 2014, we successfully treated 35 patients with soft tissue defects in the extremities (28 patients), buttock (1 patient), and head (6 patients) using new designs in groin flaps: axial free (34 patients) or pedicle (1 patient) groin flaps. RESULTS: All types of axial groin flaps survived successfully in the 2 to 38 months' (mean, 15.6 months) follow-up. The branches of the superficial circumflex iliac artery used for the axial flap design were 2 to 4 (mean, 3.09). The flap size ranged from 1×1.5 cm to 11×30 cm. No significant complications developed in any of the patients, with the exception of 2 mildly bulky flaps. CONCLUSIONS: This axial design of freestyle groin flaps not only preserves the earlier merits of the groin flap but also creates many new advantages: (1) reliability is greater, (2) ability to tailor the dimensions and flap paddles to the lesions, (3) options available to "lengthen" flap pedicles, and (4) local anesthesia usable with free flaps for reconstruction.

Correlation of plasma osteopontin and neutrophil gelatinase-associated lipocalin levels with the severity and clinical outcome of pelvic inflammatory disease.

OBJECTIVE: To investigate the correlation of two important inflammatory biomarkers, plasma osteopontin and neutrophil gelatinase-associated lipocalin (NGAL), with the severity and outcome of pelvic inflammatory disease (PID). MATERIALS AND METHODS: Sixty-one patients with PID, including 25 patients with tubo-ovarian abscess (TOA), were consecutively recruited. Their blood samples were tested for the concentrations of plasma osteopontin and NGAL using enzyme-linked immunosorbent assay. The associations of these biomarkers with TOA, length of hospitalization, and incidence of surgery were also analyzed. RESULTS: Plasma osteopontin level was significantly increased in PID patients with TOA compared to PID patients without TOA (median 107.77 ng/mL vs. 72.39 ng/mL, p = 0.004). However, there was no significant difference for plasma NGAL. If the cutoff level of plasma osteopontin was set at 81.1 ng/mL, there was a 76.0% sensitivity and a 24.0% false negative rate in predicting TOA in PID patients. Plasma osteopontin significantly correlated with length of hospital stay (r = 0.467, p < 0.001), and this correlation was better than that of NGAL. However, neither biomarker was associated with incidence of surgery. CONCLUSION: Plasma osteopontin has a better correlation with TOA and length of hospitalization compared to NGAL. If plasma osteopontin level falls below 81.1 ng/mL, PID patients will have about a 20% chance of developing TOA. Incorporating plasma osteopontin, but not NGAL, will allow for an adjuvant diagnostic biomarker for TOA and predictor of length of hospital stay.

Clinical implications of aldo-keto reductase family 1 member C3 and its relationship with lipocalin 2 in cancer of the uterine cervix.

OBJECTIVE: Over-expression of the aldo-keto reductase family 1 member C3 (AKR1C3) has been demonstrated in many human cancers. Lipocalin 2 (LCN2) is reported to inhibit cervical cancer metastasis but little is known regarding its relationship with AKR1C3 in the development and progression of uterine cervical cancer. This study aimed to investigate the involvement of AKR1C3 and its relationship with LCN2 in cervical cancer. METHODS: The roles of AKR1C3 and LCN2 were investigated using the lentivirus shRNA system in SiHa and Caski cervical cancer cells. LCN2 and matrix metalloproteinase-2 (MMP-2) promoters were constructed to demonstrate transcriptional regulation by shAKR1C3 and shLCN2, respectively. The influences of metastatic phenotypes were analyzed by wound healing, Boyden chamber, and immunofluorescence assays. The activity of MMP-2 was determined by zymography assay. The impacts of AKR1C3 and LCN2 on patient prognosis were evaluated using tissue microarrays by Cox regression and Kaplan-Meier models. RESULTS: Silencing of the AKR1C3 gene increased the expression of LCN2 and decreased the migratory and invasive abilities and changed the cytoskeleton of cervical cancer cells. When AKR1C3 was over-expressed, it decreased LCN2 promoter activity and LCN2 expression and increased cell migration. The mRNA level and enzyme activity of MMP-2 increased in silenced LCN2 cells. Positive AKR1C3 and negative LCN2 were correlated with higher recurrence and poorer survival of cervical cancer patients. CONCLUSIONS: Silencing of AKR1C3 increases LCN2 expression and inhibits metastasis in cervical cancer. Both AKR1C3 and LCN2 serve as molecular targets for cancer therapy to improve the clinical outcome of cervical cancer patients.