Miracle-dz/UniFAR-FTUs huggingface dataset:
Lipopolysaccharide increases IL‐6 secretion via activation of the ERK1/2 signaling pathway to up‐regulate RANKL gene expression in MLO‐Y4 cells

Lipopolysaccharide (LPS) plays an important role in bone resorption, which involves numerous cytokines through various signaling pathways. RANKL and interleukin (IL)‐6 are two important cytokines that are involved in bone remodeling. The aim of this study was to evaluate the effect of LPS on RANKL and IL‐6 gene expression, the relationship of RANKL and IL‐6, and the role of extracellular signal‐regulated kinases 1/2 (ERK1/2) on IL‐6 secretion induced by LPS in MLO‐Y4 cells. The cells were stimulated by LPS at different concentrations (1, 10, 100, 500, and 1000 ng/mL) for different durations (0.5, 1, 2, 4, and 8 h and 0.5, 1, 1.5, 2, and 4 h), and the mRNA expressions of RANKL and IL‐6 were determined by PCR. In the presence of 100 ng/mL LPS at different time points (0.5, 1, 1.5, 2, and 4 h), IL‐6 secretion and ERK1/2 phosphorylation in the cells were determined by ELISA and western blotting, respectively. STAT3 phosphorylation in cells simulated by 100 ng/mL LPS at different time points (0.5, 1, 2, 4, and 8 h) was assessed by western blotting. We found that LPS significantly up‐regulated RANKL expression and activated the ERK1/2 pathway to induce IL‐6 mRNA expression and protein synthesis in MLO‐Y4 cells. However, the increased IL‐6 was blocked by pre‐treatment of MLO‐Y4 cells with the ERK1/2 inhibitor U0126 (10 µM), and the enhanced RANKL was blocked by the STAT3 inhibitor S3I‐201 (100 µM). Our results indicate that LPS up‐regulates osteocyte expression of RANKL and IL‐6, and the increased RANKL is associated with the up‐regulation of IL‐6, which involves the ERK1/2 pathway.
A Good Death: Development of a Nursing Model of Care

The aim of this study was to describe the ongoing process at a Swedish hospice to further develop a model for care planning, documentation, and evaluation of the quality of death. The model was adapted to a nursing context by means of concept derivation. The core of the model is the patient as a person, in which that person’s experiences and need for control in his or her life are acknowledged. Six key words have been used as guidelines in this process: symptom control, self-determination, social relations, self-image, synthesis, and surrender. In a retrospective analysis of patient deaths it was found that of 35 patients, 15 had a very good death, 17 a good death, and 3 a bad death. Use of the 6 S key words provided the staff with continual opportunities for reflection, which was described as increasing their awareness concerning the needs of individual patients and concerning individualized nursing care.
Online-to-offline models in HIV service delivery

Purpose of review Half the world's population has access to Internet and technologies, and utilization is near-ubiquitous among providers and key populations. Despite being so well connected; identifying, reaching and linking vulnerable populations to HIV clinical services remains a global challenge. This review highlights the emerging online-to-offline (O2O) models, their potential in scaling up services, and evaluating impact, and implications for future research. Recent findings Globally, four major types of O2O models have been implemented, primarily in the West and Asia, especially among MSM and transgender women. These models have varying levels of impact in terms of reach, engagement, participation, linkage, and ability to track and monitor participants, and assess outcomes. Those integrated with offline sites enable seamless transition, dramatically reduce the O2O linkage time and demonstrate high linkage success (>73%). O2O models are ideal for at-risk, stigmatized, criminalized populations and for scaling-up biomedical prevention interventions such as preexposure and postexposure prophylaxis. Summary O2O models represent novel and powerful solutions to reverse the pandemic and could help fill significant programmatic gaps in tracking individuals through HIV cascades. Providers, especially in resource-limited settings, could choose between a variety of current approaches highlighted in this review and employ no-cost or cost-effective technologies to transform their traditional models and leverage O2O models.
Activation of KLF4 expression by small activating RNA promotes migration and invasion in colorectal epithelial cells

RNA activation mediated by small double‐stranded RNAs targeting promoter sequence named small activating RNAs (saRNAs) is one of the mechanisms for gene activation. Artificial regulation of gene expression through RNA activation does not affect the alteration of the genomic DNA sequences or exogenous plasmid DNA, therefore it is a relative manageable approach for gene perturbation. KLF4 is a member of zinc‐finger transcription factors and its functions in colorectal cells are still controversial. In order to elucidate the functions of KLF4, we synthesized saRNAs that target the promoter regions of KLF4 and transfected into varied colorectal epithelial cell lines. We found the KLF4 gene expression is specifically increased in the human normal epithelial cell NCM460 and colorectal epithelial cancer cell Caco‐2 and HCT116, but not in other human colorectal epithelial cell lines. In addition, we observed that saRNAs induced overexpression of KLF4 could promote cell migration/invasion in NCM460 and HCT116 cell lines. This effect is mediated partly by inducing EMT and facilitating nuclear translocation of β‐catenin.
Knockdown of CPEB4 expression suppresses cell migration and invasion via Akt pathway in non‐small cell lung cancer

Cytoplasmic polyadenylation element binding protein 4 (CPEB4) could be an important regulator in variety of cancers. However, the biological function and the underlying molecular mechanism of CPEB4 in non‐small cell lung cancer (NSCLC) remains unknown. In this study, we investigated the metastasis role of CPEB4 in NSCLC cells, we knocked down CPEB4 using siRNA. Transwell migration assay and cell invasion assay on Matrigel were presented, and cell migration was also determined by scratch‐healing assay. ROS generation were determined by fluorescence probe DCFH2‐DA. The protein expression was assessed by ELISA and Western blot analysis. LY294002 were used to inhibit PI3 K/Akt signaling. The data showed that knockdown of CPEB4 inhibited the migration and invasion of NSCLC. Moreover, silencing of CPEB4 reduced Snail and MMP‐3 expression in vitro. We also indicated that CPEB4 knockdown increased the ROS expression. Furthermore, we found that silencing of CPEB4 decreased pAkt expression. Taken all together, our data demonstrated that silencing of CPEB4 induces ROS generation, thus suppressing the Akt expression, which finally prevents NSCLC cells invasion and migration. Therefore, CPEB4 may regard as a target to inhibit NSCLC invasion and metastasis through Akt pathway.
T cell responses generated by HIV vaccines in clinical trials

Purpose of review Here we summarize evaluations of T cell immune responses in HIV vaccine clinical trials, highlighting investigations addressing optimization and validation of assays, reagents for determining multiclade HIV-specific responses, and current findings in phase I and II clinical testing. Recent findings Maintaining peripheral blood mononuclear cell quality and function is critical for optimal detection of T cell responses. Two recent reports emphasize the necessity for processing and freezing peripheral blood mononuclear cell within 8–12 h of venipuncture at local processing sites. Analytical designs of HIV peptide panels for use in T cell assays permit standardization of measurements between vaccines and laboratories, and evaluation of responses representing global HIV-1 strains. Phase I trials indicate superior induction of T cell response frequencies and magnitude using recombinant DNA and adenovirus serotype 5 (Ad5) vaccine with HIV-1 gene inserts. Additionally, use of a unique adjuvant with a recombinant Nef/Tat/gp120 vaccine induced high titer anti-HIV neutralizing antibodies, T cell proliferation, but not CD8 T cell responses. Summary T cell functional assays have achieved the standardization and validation to support licensure of vaccine candidates. Studies in progress will determine if these measurements are critical in defining correlates of immune protection.
Development of optimized self-nanoemulsifying lyophilized tablets (SNELTs) to improve finasteride clinical pharmacokinetic behavior

Abstract Objective: Preparation of an optimized finasteride (FSD) lyophilized tablets loaded with self-nanoemulsifying drug delivery system (SNEDDS). Significance: Enhance FSD bioavailability in male pattern baldness and benign prostatic hyperplasia. Methods: Two-step optimization was implemented to achieve the study goals. First; the mixture design was used to develop an optimized SNEDDS through which the effect of cosurfactant number of carbon atoms on SNEDDS particle size and thermodynamic stability has been tested. Second; the different tablet excipients have been used to develop an optimized self-nanoemulsifying lyophilized tablets (SNELTs). The prepared tablets have been fully characterized. Interaction among tablet components has been studied. Finally, FSD clinical pharmacokinetic has been investigated on human volunteers. Results: Anise oil and tween 80 were selected as oily phase and surfactant, respectively while different aliphatic alcohols were studied as cosurfactants. Percentages of oil, surfactant, and cosurfactants were significantly affecting SNEDDS particle size. Increasing cosurfactant number of carbon atoms achieved smaller particle size and higher stability. The optimized SNEDDS was found to contain 10.3455, 45.8972, and 43.7573% of anise oil, tween 80, and butanol, respectively. Variations in FSD cumulative release and disintegration time, from the prepared tablets, were attributed to change in the percent of plasdone XL, Avicel and silica. No interaction among components was noticed. Clinical pharmacokinetics illustrated significant enhancement in the studied parameters from the optimized lyophilized tablets loaded with drug SNEDDS when compared to marketed FSD product. Conclusion: Lyophilized tablets could be considered as a good alternative for conventional solid dosage forms especially when loaded with drug nanosystems.
Oral bioavailability enhancement of raloxifene by developing microemulsion using D-optimal mixture design: optimization and in-vivo pharmacokinetic study

Abstract The objective of this work was to utilize a potential of microemulsion for the improvement in oral bioavailability of raloxifene hydrochloride, a BCS class-II drug with 2% bioavailability. Drug-loaded microemulsion was prepared by water titration method using Capmul MCM C8, Tween 20, and Polyethylene glycol 400 as oil, surfactant, and co-surfactant respectively. The pseudo-ternary phase diagram was constructed between oil and surfactants mixture to obtain appropriate components and their concentration ranges that result in large existence area of microemulsion. D-optimal mixture design was utilized as a statistical tool for optimization of microemulsion considering oil, Smix, and water as independent variables with percentage transmittance and globule size as dependent variables. The optimized formulation showed 100 ± 0.1% transmittance and 17.85 ± 2.78 nm globule size which was identically equal with the predicted values of dependent variables given by the design expert software. The optimized microemulsion showed pronounced enhancement in release rate compared to plain drug suspension following diffusion controlled release mechanism by the Higuchi model. The formulation showed zeta potential of value −5.88 ± 1.14 mV that imparts good stability to drug loaded microemulsion dispersion. Surface morphology study with transmission electron microscope showed discrete spherical nano sized globules with smooth surface. In-vivo pharmacokinetic study of optimized microemulsion formulation in Wistar rats showed 4.29-fold enhancements in bioavailability. Stability study showed adequate results for various parameters checked up to six months. These results reveal the potential of microemulsion for significant improvement in oral bioavailability of poorly soluble raloxifene hydrochloride.
Monoamine oxidase A alleles in violent offenders with antisocial personality disorder: high activity associated with proactive aggression.

NATHAN J. KOLLA, STEPHEN ATTARD, GAVIN CRAIG, NIGEL BLACKWOOD AND SHEILAGH HODGINS, Department of Psychiatry, University of Toronto, Centre for Addiction and Mental Health, Toronto, Canada; St. Andrew’s Healthcare, Northampton, UK; Institute of Psychiatry, King’s College London, London, UK; Departement de Psychiatrie, Universite de Montreal: Centre for Addiction and Mental Health, Research Imaging Centre, 250 College Street, Room B26, Toronto, ON, Canada, M5T 1R8
Clinical pharmacology of HIV protease inhibitors in pregnancy

Purpose of reviewThe use of highly active antiretroviral therapy during pregnancy has reduced the prevalence HIV of mother-to-child transmission (MTCT) dramatically. At present, the recommended first-line treatment for prevention of MTCT in developed countries is protease inhibitor-based highly active antiretroviral therapy. In this review, we give an update on the pharmacokinetics of the protease inhibitors used during pregnancy and its clinical implications. Recent findingsProtease inhibitor-based highly active antiretroviral therapy is generally safe for mother and child and has been proven to be effective in reducing MTCT. Although no major safety concerns have been raised so far, the effect from protease inhibitors on preterm labor remains controversial. During pregnancy, drug disposition is affected, but not to the same extent for each protease inhibitor. The clinical relevance of the reduced exposure during pregnancy needs further investigation. There are no data for the new generation protease inhibitors. SummaryProtease inhibitors are currently the best option when it comes to treatment of pregnant HIV-infected women and preventing MTCT. Although all tested protease inhibitors generally showed good data, boosted saquinavir and atazanavir seemed to be less affected by pregnancy and can therefore be considered as the first choice to be used for preventing MTCT. However, it is essential to generate more data to support this recommendation. Because the observed lower exposure in some women, therapeutic drug monitoring is indicated during pregnancy.
Formulation and statistical optimization of intravenous temozolomide-loaded PEGylated liposomes to treat glioblastoma multiforme by three-level factorial design

Abstract The aim of the presented study was to develop PEGylated liposomes of Temozolomide (TMZ) that provide optimum drug concentration at tumor site. Reverse phase evaporation (REV) method was used to prepare TMZ-loaded PEGylated liposomes. Formulation was optimized by using design expert software by 32 factorial design. The physicochemical properties including size, morphology, entrapment efficiency, drug loading, etc. of formulated liposomes were evaluated. Finally, the optimized formulation was selected for in vitro drug release and stability study. In vivo pharmacokinetic study in rats showed that TMZ-loaded PEGylated liposomes leads to 1.6-fold increase in AUCTotal in blood and 4.2-fold increase in brain as compared to free drug solution. This formulated PEGylated liposomes offers a promising approach for treatment of Glioblastoma Multiforme.
Capecitabine lipid nanoparticles for anti-colon cancer activity in 1,2-dimethylhydrazine-induced colon cancer: preparation, cytotoxic, pharmacokinetic, and pathological evaluation

Abstract The cornerstone of this investigation is to determine the pharmacokinetic and histopathological behavior of solid lipid nanoparticles of capecitabine (CB-SLNs) in 1,2-dimethylhydrazine (DMH) induced colon cancer. The nanoparticles were prepared by microemulsion method. CB-SLNs were characterized for an optimal system. The cytotoxicity of CB-SLNs was evaluated by using MTT assay method. Further, pharmacokinetic and histopathological behavior of SLNs were studied in DMH induced colon cancer rats. The optimized nanoparticles have the particle size, zeta potential, and entrapment efficiency of 145.6 ± 3.6 nm, −26.9 ± 2.7 mV, and 88.33 ± 3.74%, respectively. Particles of CB were nearly spherical in shape and converted to amorphous form revealed by SEM and DSC, XRD studies. The nanoparticles showed dose-dependent cytotoxicity activity from 10 to 125 µg/mL compared with suspension. Pharmacokinetic studies revealed that 2.7-folds enhancement in the oral bioavailability and in aberrant crypt foci number, apoptotic index comparison with suspension formulation.
Validity of Evaluation Index Utilizing Three Components of Trunk Acceleration during Walking

[Purpose] The purpose of this study was to investigate the validity of an evaluation index of the vertical (VT), anteroposterior (AP), and mediolateral (ML) directions of trunk acceleration during walking. [Methods] Twenty-nine subjects volunteered for this study. Trunk acceleration and ground reaction force (GRF) during normal walking were measured. The root mean square (RMS), stride regularity (SR), and step symmetry (SS) were calculated on the basis of trunk acceleration. The displacement of COG was calculated by the double integration of GRF. The components of RMS, SS, SR, and COG were calculated in the AP, VT, and ML directions. We analyzed the correlation between RMS and COG and assessed differences among the three directions in SR and SS. [Results] We observed a significant correlation between RMS and COG in VT. SS and SR in the VT and AP directions were significantly higher than those in the ML direction. [Conclusion] These results suggest that RMS in the VT direction is useful in the gait analysis, SS and SR in the AP and VT directions were useful as indices showing the degree of deviation from normal gait.
Intracultural Diversity in Food Knowledge in Southern Brazil

This research explores the social distribution of food knowledge in Ribeirão Preto, a city in the state of São Paulo, Brazil. Through an analysis of the distribution of individual expertise in regard to the cultural model of food along the dimensions of healthfulness, practicality, and prestige, this research demonstrates that knowledge of the cultural model of food is most strongly shared in the upper class of the city. Qualitative and quantitative ethnographic research suggests that the social patterning of health-related food knowledge in Ribeirão Preto may serve to maintain class distinction.
Poxvirus vector-based HIV vaccines

Purpose of reviewIn this review, we will provide the scientific rationale for the use of poxvirus vectors in the field of HIV vaccines, the immunological profile of the vaccine-induced immune responses, an update on the current use of poxvirus vector-based vaccines in HIV vaccine clinical trials, and the development of new modified poxvirus vectors with improved immunological profile. Recent findingsAn Ad5-HIV vaccine was tested in a phase IIb clinical trial (known as the Step trial). Vaccinations in the Step trial were discontinued because the vaccine did not show any effect on acquisition of infection and on viral load. After the disappointing failure of the Step trial, the field of HIV vaccine has regained enthusiasm and vigour due to the promising protective effect observed in the phase III efficacy trial (known as RV-144) performed in Thailand which has tested a poxvirus–gp120 combination. SummaryThe RV-144 phase III has provided for the first time evidence that an HIV vaccine can prevent HIV infection. The results from the RV-144 trial are providing the scientific rationale for the future development of the HIV vaccine field and for designing future efficacy trials.
Mucosal immunity in HIV controllers: the right place at the right time

Purpose of reviewThe phenomenon of long-term nonprogression in HIV infection has been recognized for some time, and the ability of rare individuals, designated ‘elite controllers’, to control HIV in the absence of therapy is the focus of numerous ongoing studies. This review focuses on studies of HIV-specific immune responses in mucosal tissues as a potential correlate of immune control, with an emphasis on recently published work. Recent findingsGenetic studies have implicated a role for elements localized to the major histocompatibility complex (MHC) on chromosome 6 in the immune control of HIV infection. In parallel, functional studies have strongly implicated MHC class I-restricted, CD8+ T-cell responses as a major contributor to elite control. In addition, the localization of HIV-specific CD8+ and CD4+ T cells with respect to the major sites of virus replication in the body may be critical in determining clinical outcome. SummaryRecent findings suggest that MHC class I-restricted, CD8+ T cells are a major component of immune control in ‘elite controllers’. In addition, the presence of these effector cells at or near critical viral reservoirs, such as mucosal tissues, may be critical in determining their effectiveness at limiting viral replication and dissemination.
Diabetes education needs of Chinese Australians: A qualitative study

Objective: The aim of this study was to evaluate a type 2 diabetes education programme for Chinese Australians, based on the experience of participants and by exploring the unique needs of Chinese patients, their health beliefs and their cultural behaviours. Design and setting: A qualitative ethnographic study was undertaken in a community health service setting in Southeast Melbourne, Australia. Method: Eight semi-structured in-depth interviews were conducted with a purposive sample of past participants of a diabetes education programme for Chinese Australians. Data were thematically analysed, using both an ethnographic and a phenomenological lens. Results: Although participants appreciated the delivery of diabetes education in their own language, many expressed frustration and confusion when applying education messages to disease management. They described the barriers imposed by their collectivistic orientation, whereby Chinese people accept health recommendations unquestioningly, often living in misery with an excessively rigid management plan, and highlighted their lack of understanding of self-management. Patients also felt helpless in trying to mix Western and Eastern medical practices without adequate professional support. Conclusions: This qualitative study illustrates the complex and multifaceted challenges associated with diabetes management among Chinese Australians, and identifies many unique needs encountered by Chinese patients that were not addressed by the diabetes programme studied. There is an urgent need to identify optimal diabetes education models that will meet the needs of Chinese Australians.
Gathering of Wild Food Plants in Anthropogenic Environments across the Seasons: Implications for Poor and Vulnerable Farm Households

This article presents the results of a study conducted in Northeast Thailand on wild food plant gathering in anthropogenic areas and the implications for vulnerable households. A sub-sample of 40 farming households was visited every month to conduct seven-day recalls over a 12-month period on wild food plant acquisition events. Results show that these plants are an essential part of the diet, constituting a “rural safety net” particularly for vulnerable households. Findings reveal that anthropogenic environments have seasonal complementarity throughout the year with respect to wild food gathering and farmer’s gathering of wild food plants from anthropogenic environments complements seasonal crop availability. This study contributes to a deeper understanding of these plants as a household asset and their potential contribution to household well-being. The results of this study furthers our understanding of dietary traditions and the scientific challenge of the partitions that have for decades divided agriculturalists and gatherers.