Hasil untuk "Therapeutics. Pharmacology"

Ibrahim Ayad Jihad, Thekrayat Joodi Jassim, Zainab Naeif Mageed

Background and purpose: Research on the detection of uric acid (URA) and dopamine (DPA) is ongoing because of the difficulties posed by their closely overlapping oxidation potentials. Tungsten disulfide nanostructures have become attractive electrode materials to address this problem due to their low toxicity, low cost, easy production, and strong catalytic activity. Experimental approach: For voltammetric detection of compounds, we present the creation of an electrochemical sensor based on a glassy carbon electrode modified with tungsten disulfide nanostructures. Key results: According to electrochemical analyses, the manufactured sensor performed exceptionally well, having a broad LDR of 0.03 to 600.0 μM and a low LOD of 10 nM for DPA. Conclusion: The effective detection of compounds in real samples, such as injections and urine, with acceptable recovery rates further confirmed the suggested sensor's practical usefulness. In addition to offering a viable method for creating tungsten disulfide-based modified electrodes, this study holds promise for future applications in bioanalytical sensing and clinical diagnostics.

Yun Chen, Yun Chen, Kangrong Wang et al.

BackgroundHydrogen gas (H2), which is the lightest and diffusible gas molecule, has strong abilities to alleviate excessive oxidative stress, inflammation, and apoptosis. Inhalation of H2 is beneficial for preventing the damage of the lung, heart, brain, liver, kidneys, and many other organs. However, the effect of intraperitoneal injection of H2 on metabolic dysfunction–associated steatotic liver disease (MASLD) is unclear.ObjectiveThe aim of this study is to investigate whether intraperitoneal injection of H2 can improve MASLD, and if so, what are the key innate immune mechanisms involved?MethodsThe MASLD mouse model was established by feeding a methionine- and choline-deficient (MCD) diet for 3 weeks. H2 was daily given by intraperitoneal injection since the eighth day of MCD diet feeding, and lasted for 2 weeks. Serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were examined to evaluate liver injury. Hematoxylin and eosin (H&E) staining, Oil Red O staining, qPCR analysis of hepatic lipid metabolism genes, and detection of hepatic triglyceride (TG) levels were performed to evaluate hepatic steatosis. Masson trichrome staining and Collagen-I and Collagen-III protein levels were used to evaluate liver fibrosis. The liver 3-nitrotyrosine (3-NT) was detected by immunoblotting and immunofluorescence, and the levels of malondialdehyde (MDA) and reduced glutathione (GSH) were measured using kits to evaluate redox homeostasis. The activation of TLR4-mediated innate immune signaling and pyroptosis were tested by immunoblotting and immunofluorescence. Moreover, hepatic protective effect and anti-pyroptosis effect of H2 were further confirmed by H2-rich DMEM-treated HepG2 cells in vitro.ResultsSupplementing with H2 by intraperitoneal injection protected MCD diet-fed mice against hepatic steatosis and fibrosis by down-regulating de novo lipogenesis and fatty acid uptake genes, as well as hepatic Collagen-Ⅰ and Collagen-Ⅲ protein levels, while up-regulating lipid export genes. Mechanistically, H2 modulated hepatic redox homeostasis by suppressing 3-NT and MDA levels, while increasing the reduced GSH levels. Subsequently, reactive oxygen species (ROS)-related innate immune signaling, including the expression of TLR4, and the activation of NF-κB, ERK1/2, p38 MAPK, and JNK in the liver, were all inhibited by H2 treatment. These further contributed to inhibiting the expression of TNF-α, IL-1β, and IL-18 in the liver. The maturation of IL-1β and IL-18, the full-length of the classical pyroptosis trigger GSDMD, and the cleavage of GSDMD processed by Caspase-1 in NLRP3 inflammasome (including NLRP3, ASC, Caspase-1) were all blocked by H2. In addition, H2 decreased both the full-length and cleaved forms of Caspase-11, Caspase-8, Caspase-3 and GSDME, and thus inhibiting the non-canonical pyroptosis signaling in the liver of MASLD mice. The anti-pyroptosis effects of H2in vitro were further confirmed by the reduced expression of inflammatory cytokines, the decreased full-length and cleaved forms of GSDMD and GSDME, and the reduced number of HepG2 cells with pyroptotic morphology.ConclusionH2 is an anti-pyroptosis gas molecule, intraperitoneal injection of H2 is a novel therapeutic strategy for MASLD that deserves further investigation.

Alexander L. Khokhlov, Ilya I. Yaichkov, Anton A. Shetnev et al.

Introduction: The 4-(5-methyl-1,3,4-oxadiazole-2-yl)-benzenesulfonamide (ODASA) is a newcarbonic anhydrase II inhibitor for open-angle glaucoma treatment, but the excretion study of this compound has not been performed yet. Aim: Calculation of excretion parameters of ODASAand its metabolites in urine and feces in rats. Materials and Methods: The ODASA excretion was investigated on 6 Wistar rats. The 1% suspension of ODASA was instilled into each eye in a volume of 20μL (1.6 mg/kg). Excreta were collected using metabolic cages. Sampling of feces was performed every 24 h for 384 h after the administration. Urine was taken frequently in first day of experiment: 4 h, 8 h and 12 h after administration. Samples was stabilized and frozen (temperature <-70°C). Quantification of ODASA, 4-[5-(hydroxymethyl)-1,3,4-oxadiazole-2-yl]-benzenesulfonamide (M1), N-hydroxy-4-(5-methyl-1,3,4-oxadiazole-2-yl)-benzenesulfonamide (M2), 4-(5-methyl-1,3,4-oxadiazole-2-yl)-benzenesulfonic acid (M3) was carried out by HPLC-ESI-MS/MS. M2 was unstable in samples, and its content was calculated by summing the concentrations of M2 and its degradation product M3. Kinetex Phenyl Hexyl column (50*4.6 mm, 2.6 µm) was used for chromatographic separation. Results: The developed bioanalytical methods for rat excreta analysis were validated in the range of 10-10000 ppb for ODASA and M1, 1-1000 ppb – for M2, and 5-5000 ppb – for M3. Part of 16.29±1.60% of the active compound was eliminated in unchanged form, 80.27±1.68% – in the form of M1, and 3.43±0.33% – in form of M2 (М±SEM). The drug is mainly excreted by renal route: 14.22±1.43% in the form of ODASA, 69.90±1.80% – in the form of M1, and 1.88±0.24% – in the form of M2 (М±SEM). The highest rate of renal excretion of the studiedcompounds was observed in period of 8-12 hours after administration. The complete elimination of ODASA was achieved through 360 h after administration. Conclusion: Most part of ODASA is eliminated in the form of M1. The main route of excretion is renal. The use of validated bioanalytical methods guaranteed reliability of the obtained data.

Husson Ara, Nasreen Naz, Ayesha Walid et al.

Background: Adenomyosis is an important benign gynecological condition among females with variable signs and symptoms. Prompt detection of suspicious cases is important for the effective management of the disease. The objective of the current study was to determine the frequency of adenomyosis on transvaginal ultrasound (TVS), its diagnostic accuracy, and the identification of associated factors in women with symptoms of adenomyosis. Methods: This cross-sectional study was carried out at the radiology department of Dow University Hospital, Karachi, Pakistan from January 2022 to March 2023. All married females of reproductive age group presented with symptoms of adenomyosis for more than 7 days were included. Adenomyosis on TVS and histopathology were noted. Moreover, associated factors of adenomyosis were also studied. Results: Of 280 patients, adenomyosis on TVS was observed in 180 (64.3%) patients whereas on histopathology in 176 (62.9%) patients.  Diagnostic accuracy of adenomyosis on TVS showed that sensitivity was 89.20%, specificity 77.88%, positive predicted value 87.22%, negative predicted value 81.00%, and accuracy was found to be 85.00%. A significantly higher proportion of adenomyosis was observed among women who had infertility (p<0.001), symptoms of dysmenorrhea (p <0.001), dyspareunia (p<0.002), urinary symptoms (p <0.001), and GI symptoms (p<0.001). Conclusion: TVS is a valuable imaging modality for identifying adenomyosis, especially in patients with clinical symptoms. Furthermore, there is a significant association between adenomyosis and various clinical symptoms, including infertility, dysmenorrhea, dyspareunia, urinary symptoms, and gastrointestinal symptoms.

Marilyne Jarjour, Anique Ducharme

Heart failure is a growing epidemic with high mortality rates and recurrent hospital admissions that creates a burden on affected individuals, their caregivers and the whole healthcare system. Throughout the years, many randomized trials have established the effectiveness of several pharmacological therapies and electrophysiological devices to reduce hospitalizations and improve quality of life and survival, mostly for patients with heart failure with reduced ejection fraction (HFrEF). These studies led to the publication of national societies’ recommendations to guide clinicians in the management of HFrEF. Yet, many reports have shown significant care gaps in adherence to these recommendations in clinical practice, highlighting suboptimal use and/or dosing of evidence-based therapies. Adherence to guidelines has been shown to be associated with the best prognosis in HFrEF, with patients presenting with intolerances or contraindications having the highest risk of events; however, it remains unclear whether this association is causal or merely a marker of more advanced disease. Furthermore, individual characteristics may limit the possibility of reaching the targeted dosage of specific agents. Herein, we provide a comprehensive overview of clinicians’ adherence to heart failure guidelines in a specialized real-life setting, particularly regarding use and optimization of guideline-derived medical therapies, as well as the implementation of more recent agents such as sacubitril/valsartan and SGLT2 inhibitors. We seek potential explanations for suboptimal treatment and its impact on patient outcomes.

article Editorial

Департамент медицинской помощи детям, службы родовспоможения и общественного здоровья Минздрава России включил заболевание spina bifida в перечень редких (орфанных) заболеваний.

Juan A. Méndez-Líter, Ana Pozo-Rodríguez, Enrique Madruga et al.

Glycoside hydrolases (GHs) are enzymes that hydrolyze glycosidic bonds, but some of them can also catalyze the synthesis of glycosides by transglycosylation. However, the yields of this reaction are generally low since the glycosides formed end up being hydrolyzed by these same enzymes. For this reason, mutagenic variants with null or drastically reduced hydrolytic activity have been developed, thus enhancing their synthetic ability. Two mutagenic variants, a glycosynthase engineered from a β-glucosidase (BGL-1-E521G) and a thioglycoligase from a β-xylosidase (BxTW1-E495A), both from the ascomycete <i>Talaromyces amestolkiae</i>, were used to synthesize three novel epigallocatechin gallate (EGCG) glycosides. EGCG is a phenolic compound from green tea known for its antioxidant effects and therapeutic benefits, whose glycosylation could increase its bioavailability and improve its bioactive properties. The glycosynthase BGL-1-E521G produced a β-glucoside and a β-sophoroside of EGCG, while the thioglycoligase BxTW1-E495A formed the β-xyloside of EGCG. Glycosylation occurred in the 5″ and 4″ positions of EGCG, respectively. In this work, the reaction conditions for glycosides’ production were optimized, achieving around 90% conversion of EGCG with BGL-1-E521G and 60% with BxTW1-E495A. The glycosylation of EGCG caused a slight loss of its antioxidant capacity but notably increased its solubility (between 23 and 44 times) and, in the case of glucoside, also improved its thermal stability. All three glycosides showed better antiproliferative properties on breast adenocarcinoma cell line MDA-MB-231 than EGCG, and the glucosylated and sophorylated derivatives induced higher neuroprotection, increasing the viability of SH-S5Y5 neurons exposed to okadaic acid.

G. Alekhya, Prajna Paramita Giri, Arjun M.C. et al.

Vaccination is a critical tool in protecting against COVID-19. It is essential to know the time for each activity in a COVID-19 vaccination process for better management, especially during a pandemic. Thus, we conducted a time-motion study to identify activities that led to delayed/increased waiting time in an urban primary health center in Bhubaneswar, India. We observed 196 COVID-19 vaccine beneficiaries over one month (June 2021) from when they arrived at the vaccination center until they left the center. A data collection form and a Stopwatch were used to estimate the time taken for various activities involved in COVID-19 vaccine delivery. The time taken was expressed in mean and median. We also compared the time taken during the first and second doses using the Mann-Whitney U test. The total mean time spent at the vaccination center was 40:56 ± 20:52 minutes. The activity that took the longest was ‘waiting time in queue before vaccination’, which was 34:22 ± 20:56 min constituting 82% of the total time. The activity that took longer for the second dose than the first was the beneficiary verification in the Co-WIN portal with a median of 27 seconds and 36 seconds, respectively (p < .001). This study will help program managers formulate better strategies to improve the vaccination process making it more efficient.

Sabine Vogler, Friederike Windisch

Point-of-care diagnostic tests for community-acquired acute respiratory tract infections (CA-ARTI) can support doctors by improving antibiotic prescribing. However, little is known about health technology assessment (HTA), pricing and funding policies for CA-ARTI diagnostics. Thus, this study investigated these policies for this group of devices applied in the outpatient setting in Europe. Experts from competent authority responded to a questionnaire in Q4/2020. Information is available for 17 countries. Studied countries do not base their pricing and funding decision for CA-ARTI diagnostics on an HTA. While a few countries impose price regulation for some publicly funded medical devices, the prices of CA-ARTI diagnostics are not directly regulated in any of the surveyed countries. Indirect price regulation through public procurement is applied in some countries. Reimbursement lists of medical devices eligible for public funding exist in several European countries, and in some countries these lists include CA-ARTI diagnostics. In a few countries, the public payer funds the health professional for performing the service of conducting the test. Given low levels of regulation and few incentives, the study findings suggest room for strengthening pricing and funding policies of CA-ARTI diagnostics to contribute to increased acceptance and use of these point-of-care tests.

Jun-Xue Jin, Jing-Tao Sun, Chao-Qian Jiang et al.

Previous studies suggest that the inclusion of melatonin (MTn) in in vitro maturation protocols improves the developmental competence of oocytes by scavenging reactive oxygen species (ROS). However, the molecular mechanisms integrating melatonin receptor (MT)-mediated lipid metabolism and redox signaling during in vitro cumulus–oocyte complex (COC) development still remain unclear. Here, we aimed to elucidate the potential role of MTn receptors in lipid metabolic adjustments during in vitro porcine COC development. We observed that MTn-mediated G_sα–cAMP/PKA signaling facilitated lipolysis primarily through the MT2 receptor and subsequently increased fatty acid (FA) release by hydrolyzing intracellular triglycerides (TGs) in cumulus cells. Furthermore, <i>CD36</i> was a critical FA transporter that transported available FAs from cumulus cells to oocytes and promoted de novo TG synthesis in the latter. In addition, MTn regulated lipogenesis and intracellular lipolysis to maintain lipid homeostasis and limit ROS production, thereby supporting oocyte cytoplasmic maturation and the subsequent embryo development. Taken together, these findings provide insight into the possible mechanism integrating MT2-mediated lipid homeostasis and redox signaling, which limits ROS production during in vitro COC development. Therefore, understanding the dynamics of the interactions between lipid homeostasis and redox signaling driven by MT2 is necessary in order to predict drug targets and the effects of therapeutics used to improve female reproductive health.

Manpreet Singh Nanda, Mandeep Kaur

Background: There is a lack of coordination among various healthcare workers in a hospital which leads to an increase incidence of medical errors and patient sufferings. The various professionals in a hospital are not able to communicate effectively and neither they can understand each other’s roles and responsibilities. This is because they have not studied or learned together. For this reason, the concept of interprofessional (IP) education (IPE) is picking up which is when students from two or more professions learn together for better patient care. Aim and Objectives: The aim of the study was to find out the acceptance among 1st-year university students of IPE being introduced to them. Materials and Methods: Two hundred fifty 1st-year university students, belonging to various courses such as MBBS, BPT, B.Sc., and Diploma allied health sciences such as operation theatre, radiology, laboratory, biochemistry, and microbiology were brought together for a common lecture where they were explained the concepts of IPE and practice. They were divided into mix IP groups of five each and WhatsApp groups were formed and they were given assignments on the topic which they had to prepare online and present on the next date after 10 days in the class. The author joined as a facilitator in each group. Even a voluntary poster competition among these groups was held after 10 days. Results: The students were really enthusiastic and out of 50 groups formed, good interaction was visible in 45 of the groups. Twenty groups presented very highly made posters. More than 90% students gave positive feedback for this method of interactive learning and found themselves more comfortable in dealing with other course students. Conclusion: IPE is an innovative method of learning and if introduced early in the curriculum, can be highly accepted. [Natl J Physiol Pharm Pharmacol 2021; 11(3.000): 242-245]

Sarah Fruehwirth, Sandra Egger, Thomas Flecker et al.

Margarine contains a minimum of 80% fat and is therefore prone to lipid oxidation. While lipid oxidation in vegetable oils and <i>o</i>/<i>w</i> emulsions has been thoroughly investigated, studies about the oxidative stability and the identification of potential indicators of lipid oxidation in margarine are scarce. To evaluate the oxidative stability and to indicate the progress of lipid oxidation, four different types of industrial margarine (M1–M4), which differed in their composition of the minor ingredients and the oil phase, were stored at 15 °C for 180 days and analyzed at days 0, 1, 7, 14, 28, 56, 99, and 180 regarding peroxides, conjugated dienes, oxidized triacylglycerols, and volatiles. The peroxide value and the conjugated dienes increased up to 4.76 ± 0.92 meq O₂/kg oil and 14.7 ± 0.49 in M2, respectively. The oxidative stability decreased by a maximum of 50.9% in M4. We detected three different epoxidized triglycerides—TAG54:1 (O), TAG54:2 (O) and TAG54:3 (O)—in M3. Acetone could be identified, for the first time, as lipid oxidation product in stored margarine by headspace-solid-phase microextraction-gas chromatography-mass spectrometry (HS-SPME-GC-MS). It increased in all types of margarine during storage by a maximum of 1070 ppb in M2. Acetone might be used as a new indicator for lipid oxidation in margarine.

Shi-Long Jiang, Shi-Long Jiang, Zhi-Bin Wang et al.

Vemurafenib, a BRAF V600E inhibitor, provides therapeutic benefits for patients with melanoma, but the frequent emergence of drug resistance remains a challenge. An understanding of the mechanisms underlying vemurafenib resistance may generate novel therapeutic strategies for patients with melanoma. Here, we showed that eIF3a, a translational regulatory protein, was an important mediator involved in vemurafenib resistance. eIF3a was expressed at significantly lower levels in vemurafenib-resistant A375 melanoma cells (A375R) than in parental A375 cells. Overexpression of eIF3a enhanced the sensitivity to BRAF inhibitors by reducing p-ERK levels. Furthermore, eIF3a controlled ERK activity by regulating the expression of the phosphatase PPP2R1B via a translation mechanism, thus determining the sensitivity of melanoma cells to vemurafenib. In addition, a positive correlation between eIF3a and PPP2R1B expression was also observed in tumor samples from the Human Protein Atlas and TCGA databases. In conclusion, our studies reveal a previously unknown molecular mechanism of BRAF inhibitor resistance, which may provide a new strategy for predicting vemurafenib responses in clinical treatment.

Tsai TF, Chen PC, Lin YC et al.

Te-Fu Tsai,1,2 Po-Chun Chen,3,4 Yi-Chia Lin,1,2 Kuang-Yu Chou,1,2 Hung-En Chen,1 Chao-Yen Ho,1,5 Ji-Fan Lin,3 Thomas I-Sheng Hwang1,2,6 1Division of Urology, Department of Surgery, Shin-Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan; 2Division of Urology, School of Medicine, Fu-Jen Catholic University, New Taipei, Taiwan; 3Central Laboratory, Shin-Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan; 4Department of Biotechnology, College of Health Science, Asia University, Taichung, Taiwan; 5Institute of Traditional Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan; 6Department of Urology, Taipei Medical University, Taipei, TaiwanCorrespondence: Thomas I-Sheng HwangDivision of Urology, Department of Surgery, Shin Kong Wu Ho-Su Memorial Hospital, Taipei 11102, TaiwanTel +886-2-28332211 Ext 2065Fax +886-2-28389404Email thomashwang0828@gmail.comPo-Chun Chen Email blibra1002@gmail.comPurpose: Nuclear factor (erythroid-derived 2)-like 2, also known as NFE2L2 or NRF2, a transcription factor capable of upregulating antioxidant response element (ARE)-mediated expression and cytoprotective proteins, plays critical roles in chemoprevention, inflammation and aging. NRF2 has recently been proposed as a novel target for cancer chemoprevention. The fungicide miconazole has shown promising antiproliferative effects in cancer cells.Materials and Methods: After miconazole treatment, the p62-KEAP1-NRF2 activation was analyzed by qPCR and Western blot. The nuclear translocation indicating NRF2 activation was further confirmed by immunofluorescence. Finally, the ROS production was detected by CM-H2DCFDA staining.Results: We demonstrate in this study that miconazole dramatically increases NRF2 activation in bladder cancer cells, in a dose- and time-dependent manner. Interestingly, levels of expression of p62, a noncanonical pathway that mediates NRF2 activation, appeared to increase in accordance with NRF2. We also investigated levels of the negative regulator kelch-like ECH-associated protein 1 (KEAP1), which is involved in NRF2 activation. As expected, a decrease in KEAP1 expression was found after miconazole exposure. Confirmation of NRF2 nuclear translocation was monitored by immunofluorescence. Miconazole-induced generation of reactive oxygen species (ROS) promoted NRF2 activation. Pretreatment of bladder cancer cells with ROS scavengers abolished NRF2 expression and nuclear translocation, indicating that miconazole activates the noncanonical p62-KEAP1-NRF2 pathway, which is regulated by ROS production.Conclusion: Our study elucidates the mechanisms through which miconazole stimulates NRF2 which may contribute to cancer chemopreventive effects.Keywords: miconazole, NRF2, p62, KEAP1, bladder cancer

Li F, Zheng X, Bao YC et al.

Fang Li,1,* Xin Zheng,2,* YongChu Bao,3 Ting Chen,3 Jia Zeng,1 XiaoLi Xu,4 Chao Yan,5 LingLin Feng1 1NHC Key Laboratory of Reproduction Regulation (Shanghai Institute of Planned Parenthood Research), Fudan University, and Shanghai Engineer and Technology Research Center of Reproductive Health Drug and Devices, Shanghai, China; 2Harro Hoefliger Shanghai Representative Office, Shanghai, China; 3Zhitong Laboratories Co., Ltd, Shanghai, China; 4Traditional Chinese Medicine Testing Department, Chongqing Institute for Food and Drug Control, Chongqing, China; 5Schoolof Pharmacy, Shanghai Jiao Tong University, Shanghai, China *These authors contributed equally to this work Purpose: Fenofibrate and statin combination therapy is highly recommended by the current clinical guidelines for treatment of mixed dyslipidemia. In this study, an innovative delayed-release preparation of fenofibrate was designed to reduce the risk of muscle toxicity, caused by simultaneous administration of this combination therapy, by altering the pharmacokinetic profile of fenofibrate, as well as to improve the oral bioavailability of the modified-release formulation.Methods: Micronized fenofibrate was used to prepare drug-loaded cores via a powder layering process before multiparticulate pellet coating. Different coating formulations (Eudragit&reg; RS PO/E100, Eudragit&reg; RS PO/RL PO, Eudragit&reg; NE30D/HPMC, and EC/HPMC) were screened, and their in vitro release was compared with the commercial sustained-release pellets Lipilfen&reg;. Two optimized formulations were evaluated in beagle dogs using two commercial preparations of fenofibrate (the immediate-release preparation Lipanthyl&reg; and the sustained-release pellets Lipilfen&reg;) as references.Results: The in vivo release of fenofibrate from R1 and R2 selected from in vitro tests exhibited a lag phase, and then rapid and complete drug release. The relative bioavailabilities of R1 and R2 were 100.4% and 201.1%, respectively, which were higher than that of Lipilfen&reg; (67.2%).Conclusion: The modified fenofibrate pellets developed showed enhanced bioavailability and delayed-release properties. They have the potential to improve safety and compliance when co-administrated with statins. This is the first report of a delayed-release fenofibrate preparation. Keywords: fenofibrate, modified-release pellets, coated multiparticulate pellet, pharmacokinetics, in vivo studies

Lingling Tang, Jinjin Liu, Linyun Zhu et al.

Lung squamous cell carcinoma (LSCC) is a common histological lung cancer subtype, but unlike lung adenocarcinoma, limited therapeutic options are available for treatment. Curcumin, a natural compound, may have anticancer effects in various cancer cells, but how it may be used to treat LSCC has not been well studied. Here, we applied curcumin to a human NCI-H292 LSCC cell line to test anticancer effects and explored underlying potential mechanisms of action. Curcumin treatment inhibited NCI-H292 cell growth and increased FOXA2 expression in a time-dependent manner. FOXA2 expression was decreased in LSCC tissues compared with adjacent normal tissues and knockdown of FOXA2 increased NCI-H292 cells proliferation. Inhibition of cell proliferation by curcumin was attenuated by FOXA2 knockdown. Moreover inhibition of STAT3 pathways by curcumin increased FOXA2 expression in NCI-H292 cells whereas a STAT3 activator (IL-6) significantly inhibited curcumin-induced FOXA2 expression. Also, SOCS1 and SOCS3, negative regulators of STAT3 activity, were upregulated by curcumin treatment. Thus, curcumin inhibited human NCI-H292 cells growth by increasing FOXA2 expression via regulation of STAT3 signaling pathways.

Feng Pang, Xiu-Qin Jia, Qi-Gang Zhao et al.

Abstract Background The increasing incidence of carbapenem-resistant Enterobacteriaceae (CRE), has resulted in a difficult problem in the current clinical anti-infective treatment. We performed a retrospective analysis of prevalence and treatment for CRE infections patients. Methods This study was conducted in three tertiary care hospitals from January 1, 2010 to December 30, 2016. Baseline data, treatment, and outcomes were collected in patients with ventilator-associated bacterial pneumonia (VABP), bacteremia, complicated urinary tract infection (cUTI)/acute pyelonephritis (AP), hospital-acquired bacterial pneumonia (HABP), superficial wound infection (SWI), biliary tract infection (BTI), deep wound infection (DWI) and sterile body fluids infection (SBFI) due to CRE. Results One hundred twenty-four cases of CRE infection were identified: 31 VABP, 22 bacteremia, 18 cUTI/AP, 16 HABP, 16 SWI, 9 BTI, 7 DWI and 5 SBFI. The patient population had significant immunocompromised (33 of 124, 26.6%) and severe sepsis (43 of 124, 34.7%). The most common CRE pathogens were Klebsiella pneumoniae (84 of 124, 67.7%) and Enterobacter cloacae (24 of 124, 19.4%). And the production of IMP-type carbapenemase was the main antibiotic resistance mechanism. The majority of patients to take monotherapy for empiric therapy and dual therapy for direct treatment. Outcomes were universally poor (28-day mortality was 22.6%, 28 of 124) across all sites of infection. Conclusions We identified a large number of cases of CRE infection in 7 years from different parts, most of these pathogens have been confirmed to produce IMP-type carbapenemases. The retrospective analysis of cases of such bacterial infections will help to control future infections of these pathogens. Despite the high mortality rate, we still found that the selection of quinolone antibiotics can be effective in the treatment of CRE producing IMP type enzymes.

Yuliya G. Levina

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Danielle Corrêa França, Paulo Augusto Moreira Camargos, Bruna da Silva Pinto Pinheiro Vieira et al.

RESUMO É importante avaliar a função pulmonar em pré-escolares. Poucos estudos relacionados aos testes de função pulmonar nessa população estão disponíveis. O objetivo deste estudo foi avaliar a taxa de sucesso e reprodutibilidade teste-reteste do pico de fluxo da tosse (PFT) em uma amostra de crianças com idade entre 4 e 6 anos. O PFT foi estudado em 44 crianças saudáveis (26 meninos e 18 meninas), selecionadas de acordo com o questionário ATS-DLD-78-C, utilizado para detectar a presença de doenças respiratórias de base e exposição ambiental. O medidor de pico de fluxo expiratório (Piko-I Electronic Peak Flow Meter, Pulmonary Data Services, USA) foi usado para mensurar o PFT. A taxa de sucesso foi definida como a porcentagem de crianças capazes de realizar o teste de acordo com os critérios de aceitabilidade e reprodutibilidade. Para avaliar a reprodutibilidade teste-reteste, 10 crianças (de acordo com o cálculo amostral) foram reavaliadas após três semanas. A reprodutibilidade teste-reteste foi avaliada pelo teste t pareado, considerando significativo p<0,05 e coeficiente de correlação intraclasse (CCI). Os resultados mostraram uma taxa de sucesso de 91% para PFT, sendo de 80, 88 e 100% para crianças com 4, 5 e 6 anos, respectivamente. Quanto à reprodutibilidade teste-reteste, não houve diferença significativa entre os dados da primeira avaliação e da reavaliação (p=0,39) e foi observado CCI de 0,84. Esses resultados sugerem elevada taxa de sucesso na realização do PFT e reprodutibilidade teste-reteste de magnitude excelente para essa variável em pré-escolares saudáveis.

Yuki Ota, Takuya Kawanai, Ryo Watanabe et al.

Abstract.: Nitric oxide (NO) induces cytotoxicity in neuronal and glial cells via activation of the Na+/Ca2+ exchanger (NCX). This study examined the role of the predominant brain-specific NCX splice variant NCX1.5 in NO-induced cytotoxicity in the HEK293 cell expression system. Cells were transfected with the plasmid construct pcDNA3.1/V5-His containing full-length rat NCX1.5 cDNA. There was no difference in the cytotoxic effects of the NO donors sodium nitroprusside and S-nitroso-N-acetylpenicillamine between control and transfected cells. These results suggest that NO cytotoxicity is not dependent on NCX1.5. Keywords:: Na+/Ca2+ exchanger, nitric oxide, cytotoxicity