New iridium bis-terpyridine complexes: synthesis, characterization, antibiofilm and anticancer potentials.

This study represents synthesis, characterization, screening of antibiofilm efficacy, and cytotoxicity of iridium bis-terpyridine complexes. The complexes were characterized by NMR, MS, FTIR, UV/Visible, and fluorescence spectroscopies. The efficacy of biofilm inhibition and eradication of iridium complexes was evaluated using a crystal violet assay test and verified by fluorescence microscopy. Cytotoxicity and apoptosis analysis of iridium complexes were determined in this study. The results of our study revealed that three iridium complexes had the potential to inhibit biofilm formation and moderate the ability to destroy pre-formed biofilm of S. aureus ATCC 29,213. 250 µM concentration of synthesized complexes showed the highest antibiofilm activity (75% for Ir1, 90% for Ir2, and 71% for Ir3). The significant inhibition obtained at 6.25 µM concentration of Ir2 and Ir3 revealed the potential of our samples. Also, Ir1 and Ir2 complexes had a good capacity to destroy pre-formed biofilm. The results clearly showed that iridium complexes have cytotoxic activity towards colon cancer (Caco-2) and liver cancer (HepG2) cell lines without affecting non-cancerous cells (HEK293) at applied doses. Moreover, tested compounds induced apoptosis in these cancer cells. All of these results showed that iridium complexes had possessed the ability to inhibit or destroy pre-formed biofilm and could be developed as an effective agent against bacterial biofilms. Moreover, these pure substances may have valuable anti-cancer activity and it should be confirmed with further studies for therapeutic effects.

Tetracosahexaenoylethanolamide, a novel N-acylethanolamide, is elevated in ischemia and increases neuronal output.

N-acylethanolamines (NAEs) are endogenous lipid-signaling molecules derived from fatty acids that regulate numerous biological functions, including in the brain. Interestingly, NAEs are elevated in the absence of fatty acid amide hydrolase (FAAH) and following CO2-induced ischemia/hypercapnia, suggesting a neuroprotective response. Tetracosahexaenoic acid (THA) is a product and precursor to DHA; however, the NAE product, tetracosahexaenoylethanolamide (THEA), has never been reported. Presently, THEA was chemically synthesized as an authentic standard to confirm THEA presence in biological tissues. Whole brains were collected and analyzed for unesterified THA, total THA, and THEA in wild-type and FAAH-KO mice that were euthanized by either head-focused microwave fixation, CO2 + microwave, or CO2 only. PPAR activity by transient transfection assay and ex vivo neuronal output in medium spiny neurons (MSNs) of the nucleus accumbens by patch clamp electrophysiology were determined following THEA exposure. THEA in the wild-type mice was nearly doubled (P < 0.05) following ischemia/hypercapnia (CO2 euthanization) and up to 12 times higher (P < 0.001) in the FAAH-KO compared with wild-type. THEA did not increase (P > 0.05) transcriptional activity of PPARs relative to control, but 100 nM of THEA increased (P < 0.001) neuronal output in MSNs of the nucleus accumbens. Here were identify a novel NAE, THEA, in the brain that is elevated upon ischemia/hypercapnia and by KO of the FAAH enzyme. While THEA did not activate PPAR, it augmented the excitability of MSNs in the nucleus accumbens. Overall, our results suggest that THEA is a novel NAE that is produced in the brain upon ischemia/hypercapnia and regulates neuronal excitation.

The relationship between teachers' zest for work and teaching motivation: the mediating role of achievement goals.

Objective: This study aims to investigate the mediating role of achievement goals in the relationship between teachers' zest for work and teaching motivation. Method: The research was designed using the relational survey model. The research sample consisted of 518 teachers working in various cities in Turkey in 2023-2024 academic year fall semester. A convenience sampling method was used in sampling. Three Likert-type scales were used as data collection tools. In the data analysis, firstly, the data suitability to normal distributions was examined. As a result of the analysis, kurtosis and skewness values were examined and it was assumed that the data were normally distributed. SPSS Process extension was used to analyze the data. Results and discussion: According to the research results, teachers' zest for work positively and significantly predicted strong and positive achievement goals. In addition, teachers' achievement goals significantly and positively predicted their teaching motivation. Additionally, teachers' zest for work positively and significantly predicted their teaching motivation. Moreover, it can be inferred that achievement goals for students have a mediating role in the relationship between teachers' zest for work and teaching motivation. In this context, it is suggested that policies that increase teachers' teaching motivation should be prioritized.

A novel fatty acid mimetic with pan-PPAR partial agonist activity inhibits diet-induced obesity and metabolic dysfunction-associated steatotic liver disease.

OBJECTIVE: The prevalence of metabolic diseases is increasing globally at an alarming rate; thus, it is essential that effective, accessible, low-cost therapeutics are developed. Peroxisome proliferator-activated receptors (PPARs) are transcription factors that tightly regulate glucose homeostasis and lipid metabolism and are important drug targets for the treatment of type 2 diabetes and dyslipidemia. We previously identified LDT409, a fatty acid-like compound derived from cashew nut shell liquid, as a novel pan-active PPARα/γ/δ compound. Herein, we aimed to assess the efficacy of LDT409 in vivo and investigate the molecular mechanisms governing the actions of the fatty acid mimetic LDT409 in diet-induced obese mice. METHODS: C57Bl/6 mice (6-11-month-old) were fed a chow or high fat diet (HFD) for 4 weeks; mice thereafter received once daily intraperitoneal injections of vehicle, 10 mg/kg Rosiglitazone, 40 mg/kg WY14643, or 40 mg/kg LDT409 for 18 days while continuing the HFD. During treatments, body weight, food intake, glucose and insulin tolerance, energy expenditure, and intestinal lipid absorption were measured. On day 18 of treatment, tissues and plasma were collected for histological, molecular, and biochemical analysis. RESULTS: We found that treatment with LDT409 was effective at reversing HFD-induced obesity and associated metabolic abnormalities in mice. LDT409 lowered food intake and hyperlipidemia, while improving insulin tolerance. Despite being a substrate of both PPARα and PPARγ, LDT409 was crucial for promoting hepatic fatty acid oxidation and reducing hepatic steatosis in HFD-fed mice. We also highlighted a role for LDT409 in white and brown adipocytes in vitro and in vivo where it decreased fat accumulation, increased lipolysis, induced browning of WAT, and upregulated thermogenic gene Ucp1. Remarkably, LDT409 reversed HFD-induced weight gain back to chow-fed control levels. We determined that the LDT409-induced weight-loss was associated with a combination of increased energy expenditure (detectable before weight loss was apparent), decreased food intake, increased systemic fat utilization, and increased fecal lipid excretion in HFD-fed mice. CONCLUSIONS: Collectively, LDT409 represents a fatty acid mimetic that generates a uniquely favorable metabolic response for the treatment of multiple abnormalities including obesity, dyslipidemia, metabolic dysfunction-associated steatotic liver disease, and diabetes. LDT409 is derived from a highly abundant natural product-based starting material and its development could be pursued as a therapeutic solution to the global metabolic health crisis.

The omega-3 hydroxy fatty acid 7(S)-HDHA is a high-affinity PPARα ligand that regulates brain neuronal morphology.

The nuclear receptor peroxisome proliferator-activated receptor alpha (PPARα) is emerging as an important target in the brain for the treatment or prevention of cognitive disorders. The identification of high-affinity ligands for brain PPARα may reveal the mechanisms underlying the synaptic effects of this receptor and facilitate drug development. Here, using an affinity purification-untargeted mass spectrometry (AP-UMS) approach, we identified an endogenous, selective PPARα ligand, 7(S)-hydroxy-docosahexaenoic acid [7(S)-HDHA]. Results from mass spectrometric detection of 7(S)-HDHA in mouse and rat brain tissues, time-resolved FRET analyses, and thermal shift assays collectively revealed that 7(S)-HDHA potently activated PPARα with an affinity greater than that of other ligands identified to date. We also found that 7(S)-HDHA activation of PPARα in cultured mouse cortical neurons stimulated neuronal growth and arborization, as well as the expression of genes associated with synaptic plasticity. The findings suggest that this DHA derivative supports and enhances neuronal synaptic capacity in the brain.

Phenolic Lipids Derived from Cashew Nut Shell Liquid to Treat Metabolic Diseases.

Metabolic diseases are increasing at staggering rates globally. The peroxisome proliferator-activated receptors (PPARα/γ/δ) are fatty acid sensors that help mitigate imbalances between energy uptake and utilization. Herein, we report compounds derived from phenolic lipids present in cashew nut shell liquid (CNSL), an abundant waste byproduct, in an effort to create effective, accessible, and sustainable drugs. Derivatives of anacardic acid and cardanol were tested for PPAR activity in HEK293 cell co-transfection assays, primary hepatocytes, and 3T3-L1 adipocytes. In vivo studies using PPAR-expressing zebrafish embryos identified CNSL derivatives with varying tissue-specific activities. LDT409 (23) is an analogue of cardanol with partial agonist activity for PPARα and PPARγ. Pharmacokinetic profiling showed that 23 is orally bioavailable with a half-life of 4 h in mice. CNSL derivatives represent a sustainable source of selective PPAR modulators with balanced intermediate affinities (EC50 ∼ 100 nM to 10 µM) that provide distinct and favorable gene activation profiles for the treatment of diabetes and obesity.

Essential role of STAT-3 dependent NF-κB activation on IL-6-mediated downregulation of hepatic transporters.

IL-6 markedly decreases the expression of numerous hepatic transporters. We previously demonstrated that IL-6-mediated downregulation of transporters occurs through STAT3, with partial involvement of PXR. However, while IL-6-mediated induction of STAT3 occurs rapidly, repression of transporter expression is not observed until 6 h post-treatment. This temporal mismatch suggested that the downregulation of transporters following IL-6 at 6 h might require additional signaling downstream of STAT3. Since NF-κB has been implicated in endotoxin-mediated downregulation of transporters, we hypothesized that NF-κB may be similarly involved in suppressing transporter expression following IL-6. Our objective was to investigate whether IL-6-mediated changes in transporter expression occur through STAT3-dependent NF-κB activation, and whether PXR is involved. PXR null (-/-) or wild type (+/+) mice were pre-dosed with the NF-κB inhibitor PHA408 or vehicle 30 min prior to receiving a single dose of IL-6 or saline. Mice were euthanized after 6 h and transporter expression was analyzed using qRT-PCR. IL-6 imposed downregulation of Abcb1a, Abcb1b, Abcc3, Abcg2 and Cyp3a11 in both PXR (+/+) and PXR (-/-) mice, while downregulation of Abcb11, Abcc2, Slc10a1, and Slco2b1 was only significant in PXR (+/+) mice. PHA408 pretreatment fully inhibited NF-κB activation in PXR (+/+) but only partially inhibited NF-κB in PXR (-/-). Inhibition of NF-κB attenuated IL-6-mediated changes in transporters in PXR (+/+) mice. Transient transfection assays did not detect significant activation of human or mouse PXR by PHA408. Our findings suggest that IL-6 imposes significant downregulation of numerous ABC and SLC transporters in the liver via collaborative STAT3/NF-κB activation. Since drug transporters play an integral role in the pharmacokinetics of numerous clinically relevant drugs, understanding the signaling pathways involved in transporter regulation during inflammation will contribute to a better understanding of drug-disease interactions.

Tailored mobile text messaging interventions targeting type 2 diabetes self-management: A systematic review and a meta-analysis.

OBJECTIVES: This study aimed to identify, assess and summarize available scientific evidence on tailored text messaging interventions focused on type 2 diabetes self-management. The systematic review concentrated on message design and delivery features, and tailoring strategies. The meta-analysis assessed the moderators of the effectiveness of tailored text messaging interventions. METHODS: A comprehensive search strategy included major electronic databases, key journal searches and reference list searching for related studies. PRISMA and Cochrane Collaboration's guidelines and recommended tools for data extraction, quality appraisal and data analysis were followed. Data were extracted on participant characteristics (age, gender, ethnicity), and interventional and methodological characteristics (study design, study setting, study length, choice of modality, comparison group, message type, format, content, use of interactivity, message frequency, message timing, message delivery, tailoring strategies and theory use). Outcome measures included diet, physical activity, medication adherence and glycated hemoglobin data (HbA1C). Where possible, a random effects meta-analysis was performed to pool data on the effectiveness of the tailored text messaging interventions and moderator variables. RESULTS: The search returned 13 eligible trials for the systematic review and 11 eligible trials for the meta-analysis. The majority of the studies were randomized controlled trials, conducted in high-income settings, used multi-modalities, and mostly delivered informative, educational messages through an automated message delivery system. Tailored text messaging interventions produced a substantial effect (g = 0.54, 95% CI = 0.08-0.99, p < 0.001) on HbA1C values for a total of 949 patients. Subgroup analyses revealed the importance of some moderators such as message delivery (Q B = 18.72, df = 1, p = 0.001), message direction (Q B = 5.26, df = 1, p = 0.022), message frequency (Q B = 18.72, df = 1, p = 0.000) and using multi-modalities (Q B = 6.18, df = 1, p = 0.013). CONCLUSIONS: Tailored mobile text messaging interventions can improve glycemic control in type 2 diabetes patients. However, more rigorous interventions with larger samples and longer follow-ups are required to confirm these findings and explore the effects of tailored text messaging on other self-management outcomes.

Peroxisome Proliferator-Activated Receptor-gamma agonists exhibit anti-inflammatory and antiviral effects in an EcoHIV mouse model.

The widespread use of combination antiretroviral therapy (cART) has resulted in significantly reduced deaths from HIV-1 associated complications and opportunistic infections. However, it is estimated that up to 50% of HIV-1 infected individuals still develop HIV-1 associated neurocognitive disorders (HAND). With no treatment currently available for patients, there is a critical need to identify therapeutic approaches that can treat this disorder. Evidence suggests that targeting Peroxisome Proliferator-Activated Receptor-gamma (PPARγ) can be anti-inflammatory in neurological disorders. Here we show that treatment with PPARγ agonists (rosiglitazone or pioglitazone) in primary cultures of mouse glial cells reversed EcoHIV-induced inflammatory genes (TNFα, IL-1ß, CCL2, CCL3, CXCL10) and indicator of oxidative stress (iNOS). Furthermore, in vivo, mice administered with EcoHIV through intracranial injection resulted in upregulation of inflammatory genes (TNFα, IL-1ß, IFNγ, CCL2, CCL3, CXCL10) and oxidative stress marker (iNOS) in the brain which was reversed through intraperitoneal administration of PPARγ agonists (rosiglitazone or pioglitazone). Finally, we demonstrated that treatment with these compounds in vivo reduced EcoHIV p24 protein burden in the brain. Our results suggest that treatment with PPARγ agonists are anti-inflammatory and antiviral in an in vivo model of EcoHIV infection. These drugs hold promise as potential candidates for HAND treatment in the future.

Rules of engagement in mobile health: what does mobile health bring to research and theory?

BACKGROUND: The effectiveness of mobile health (mHealth) is a controversial issue. For its wide-scale adoption and successful integration to the healthcare system, theoretical, methodological, and practical issues of mHealth should be well understood. OBJECTIVES: The purpose of the study was to review the essential characteristics of mHealth and discuss what mHealth presents to research and theory. METHOD: This review synthesized the studies focused on the adoption, design, and implementation of mHealth. The search strategy included reviewing electronic databases, key journals, web-based research and knowledge centers, and manual searching reference lists of the main studies. RESULTS: mHealth's core characteristics were specified as accessibility, inclusivity, patient's autonomy, customizability, increasing the accuracy of diagnostics and treatment, improvement in service quality, and testability. Opportunities and challenges in regards to theory and research were discussed. CONCLUSIONS AND IMPLICATIONS: Using an integrated approach, this study identified and summarized the key issues to understand mHealth. Implications and recommendations for research and practice were provided.

Mixed-Methods Research in Diabetes Management via Mobile Health Technologies: A Scoping Review.

BACKGROUND: Considering the increasing incidence and prevalence of diabetes worldwide and the high level of patient involvement it requires, diabetes self-management is a serious issue. The use of mobile health (mHealth) in diabetes self-management has increased, but so far research has not provided sufficient information about the uses and effectiveness of mHealth-based interventions. Alternative study designs and more rigorous methodologies are needed. Mixed-methods designs may be particularly useful because both diabetes self-management and mHealth studies require integrating theoretical and methodological approaches. OBJECTIVE: This scoping review aimed to examine the extent of the use of mixed-methods research in mHealth-based diabetes management studies. The methodological approaches used to conduct mixed-methods studies were analyzed, and implications for future research are provided. METHODS: Guided by Arksey and O'Malley's framework, this scoping review implemented a comprehensive search strategy including reviewing electronic databases, key journal searches, Web-based research and knowledge centers, websites, and handsearching reference lists of the studies. The studies focusing on mHealth technologies and diabetes management were included in the review if they were primary research papers published in academic journals and reported using a combination of qualitative and quantitative methods. The key data extracted from the reviewed studies include purpose of mixing, design type, stage of integration, methods of legitimation, and data collection techniques. RESULTS: The final sample (N=14) included studies focused on the feasibility and usability of mHealth diabetes apps (n=7), behavioral measures related to the mHealth apps (n=6), and challenges of intervention delivery in the mHealth context (n=1). Reviewed studies used advanced forms of mixed-methods designs where integration occurred at multiple points and data were collected using multiple techniques. However, the majority of studies did not identify a specific mixed-methods design or use accepted terminology; nor did they justify using this approach. CONCLUSIONS: This review provided important insights into the use of mixed methods in studies focused on diabetes management via mHealth technologies. The prominent role of qualitative methods and tailored measures in diabetes self-management studies was confirmed, and the importance of using multiple techniques and approaches in this field was emphasized. This review suggests defining specific mixed-methods questions, using specific legitimation methods, and developing research designs that overcome sampling and other methodological problems in future studies.

Ligandless-solidified floating organic drop microextraction method for the preconcentration of trace amount of cadmium in water samples.

In this article, a new ligandless solidified floating organic drop microextraction (LL-SFODME) method has been developed for preconcentration of trace amount of cadmium as a prior step to its determination by flow injection-flame atomic absorption spectrometry (FI-FAAS). The methodology is based on the SFODME of cadmium with 1-dodecanol in the absence of chelating agent. Several factors affecting the microextraction efficiency, such as, pH, sodium dodecylbenzenesulfonate (SDBS) concentration, extraction time, stirring rate and temperature were investigated and optimized. Under optimized experimental conditions an enhancement factor of 205 was obtained for 100mL of sample solution. The calibration graph was linear in the range of 1.0-25.0 ng mL(-1), the limit of detection (3s) was 0.21 ng mL(-1) and the limit of quantification (10s) was 0.62 ng mL(-1). The relative standard deviation (RSD) for 10 replicate measurements of 10 ng mL(-1) cadmium was 4.7%. The developed method was successfully applied to the extraction and determination of cadmium in standard and several water samples and satisfactory results were obtained.

A novel solidified floating organic drop microextraction method for preconcentration and determination of copper ions by flow injection flame atomic absorption spectrometry.

A rapid, simple and cost effective solidified floating organic drop microextraction (SFODME) and flow injection flame atomic absorption spectrometric determination (FI-FAAS) method for copper was developed. In this method, a free microdrop of 1-undecanol containing 1,5-diphenyl carbazide (DPC) as the complexing agent was transferred to the surface of an aqueous sample including Cu(II) ions, while being agitated by a stirring bar in the bulk of the solution. Under the proper stirring conditions, the suspended microdrop can remain at the top-center position of the aqueous sample. After the completion of the extraction, the sample vial was cooled by placing it in a refrigerator for 10min. The solidified microdrop was then transferred into a conical vial, where it melted immediately and diluted to 300microL with ethanol. Finally, copper ions in 200microL of diluted solution were determined by FI-FAAS. Several factors affecting the microextraction efficiency, such as type of extraction solvent, pH, complexing agent concentration, extraction time, stirring rate, sample volume and temperature were investigated and optimized. Under optimized conditions for 100mL of solution, the preconcentration factor was 333 and the enrichment factor was 324. The limit of detection (3s) was 0.4ngmL(-1), the limit of quantification (10s) was 1.1ngmL(-1) and the relative standard deviation (RSD) for 10 replicate measurements of 10ngmL(-1) copper was 0.9%. The proposed method was successfully applied to the determination of copper in different water samples.

Preconcentration and determination of iron and copper in spice samples by cloud point extraction and flow injection flame atomic absorption spectrometry.

A flow injection (FI) cloud point extraction (CPE) method for the determination of iron and copper by flame atomic absorption spectrometer (FAAS) has been improved. The analytes were complexed with 3-amino-7-dimethylamino-2-methylphenazine (Neutral Red, NR) and octylphenoxypolyethoxyethanol (Triton X-114)wasadded as a surfactant. The micellar solutionwasheated above 50 degrees C and loaded through a column packed with cotton for phase separation. Then the surfactant-rich phase was eluted using 0.05 mol L(-1) H2SO4 and the analytes were determined by FAAS. Chemical and flow variables influencing the instrumental and extraction conditions were optimized. Under optimized conditions for 25 mL of preconcentrated solution, the enrichment factors were 98 and 69, the limits of detection (3s) were 0.7 and 0.3 ng mL(-1), the limits of quantification (10s) were 2.2 and 1.0 ng mL(-1) for iron and copper, respectively. The relative standard deviation (RSD) for ten replicate measurements of 10 ng mL(-1) iron and copper were 2.1% and 1.8%, respectively. The proposed method was successfully applied to determination of iron and copper in spice samples.

Combination of cloud point extraction and flame atomic absorption spectrometry for preconcentration and determination of nickel and manganese ions in water and food samples.

A simple, rapid, inexpensive, and nonpolluting cloud point extraction (CPE) technique has been improved for the preconcentration and determination of nickel and manganese. After complexation with p-nitrophenylazoresorcinol (Magneson I), the analytes could be competitively extracted in a surfactant octylphenoxy polyethoxyethanol (Triton X-114), prior to determination by flame atomic absorption spectrometry (FAAS). The effects of experimental conditions such as pH, concentration of chelating agent and surfactant, equilibration temperature and time on CPE were studied. Under the optimum conditions, preconcentration of a 25 mL sample solution permitted the detection of 2.7 ng mL(-1) Ni(2+) and 2.9 ng mL(-1) Mn(2+) with enrichment factors of 17 and 19 for Ni(2+) and Mn(2+), respectively. The developed method was applied to the determination of trace nickel and manganese in water and food samples with satisfactory results.

Stability of binary and ternary copper(II) complexes with 1,10-phenanthroline, 2,2'-bipyridyl and some alpha-amino acids in aqueous medium.

Interactions of certain amino acids with some metal ions have significant consequences in biological systems. Metal ions can act as co-factors in the regulation of enzymatic reactions. Interactions of metal ions with amino acid side chains or with different organic complexes is also essential for many biological events. In this study, the stability constants of 1 : 1 : 1 ternary complexes of Cu(II) with 1,10-phenanthroline (Phen) as the primary ligand, and 2,2'-bipyridyl (Bpy) and some selected alpha-amino acids [(glycine (Gly), leucine (Leu), glutamine (Gln)] as secondary ligands, were identified in I=0.1 M ionic medium at t=(25+/-0.1) degrees C in aqueous solutions, by potentiometry. The protonation constants of the free ligands and the stability constants of the binary and ternary systems were also determined under the same experimental conditions. The protonation constants of all of the ligands and the stability constants of the formed complexes were evaluated by using the BEST computer program. The stabilities of the ternary complexes have been quantitatively compared with those of the corresponding binary complexes in terms of the some parameters. The concentration distributions of the complexes in solution were also evaluated. Species distributions as a function of pH reveal that the MAB ternary complexes predominate over a pH range, where M=Cu(II); A=Phen; B=Bpy, Gly, Leu and Gln.