A New Acetogenin from Annona mucosa Chen, C. Y.; Kao, C. L.; Yeh, H. C. ...
Chemistry of natural compounds,
05/2023, Letnik:
59, Številka:
3
Journal Article
Recenzirano
A new acetogenin, 4-methoxyannonins VIII (
1
) was isolated from the unripe fruits of
Annona mucosa
Jacq. (Annonaceae). The structure of the new acetogenin was elucidated by chemical and physical ...evidence.
SUMMARY
Objective: To evaluate the efficacy and tolerability of topiramate in patients with posttraumatic stress disorder (PTSD). Method: We conducted a 12‐week double‐blind, randomized, ...placebo‐controlled study comparing topiramate to placebo. Men and women aged 18–62 years with diagnosis of PTSD according to DSM‐IV were recruited from the outpatient clinic of the violence program of Federal University of São Paulo Hospital (Prove‐UNIFESP), São Paulo City, between April 2006 and December 2009. Subjects were assessed for the Clinician‐Administered Posttraumatic Stress Scale (CAPS), Clinical Global Impression, and Beck Depression Inventory (BDI). After 1‐week period of washout, 35 patients were randomized to either group. The primary outcome measure was the CAPS total score changes from baseline to the endpoint. Results: 82.35% of patients in the topiramate group exhibited improvements in PTSD symptoms. The efficacy analysis demonstrated that patients in the topiramate group exhibited significant improvements in reexperiencing symptoms: flashbacks, intrusive memories, and nightmares of the trauma (CAPS‐B; P= 0.04) and in avoidance/numbing symptoms associated with the trauma, social isolation, and emotional numbing (CAPS‐C; P= 0.0001). Furthermore, the experimental group demonstrated a significant difference in decrease in CAPS total score (topiramate −57.78; placebo −32.41; P= 0.0076). Mean topiramate dose was 102.94 mg/d. Topiramate was generally well tolerated. Conclusion: Topiramate was effective in improving reexperiencing and avoidance/numbing symptom clusters in patients with PTSD. This study supports the use of anticonvulsants for the improvement of symptoms of PTSD.
Purpose To evaluate effects of two behavioral weight-loss interventions (in-person, remote) on health-related quality of life (HRQOL) compared to a control intervention. Methods Four hundred and ...fifty-one obese US adults with at least one cardiovascular risk factor completed five measures of HRQOL and depression: MOS SF-12 physical component summary (PCS) and mental component summary; EuroQoL-5 dimensions single index and visual analog scale; PHQ-8 depression symptoms; and PSQI sleep quality scores at baseline and 6 and 24 months after randomization. Change in each outcome was analyzed using outcome-specific mixed-effects models controlling for participant demographic characteristics. Results PCS-12 scores over 24 months improved more among participants in the in-person active intervention arm than among control arm participants (P < 0.05, ES = 0.21); there were no other statistically significant treatment arm differences in HRQOL change. Greater weight loss was associated with improvements in most outcomes (P < 0.05 to < 0.0001). Conclusions Participants in the in-person active intervention improved more in physical function HRQOL than participants in the control arm did. Greater weight loss during the study was associated with greater improvement in all PRO except for sleep quality, suggesting that weight loss is a key factor in improving HRQOL.
Apoptosis of mouse neocortical neurons induced by serum deprivation or by staurosporine was associated with an early enhancement of delayed rectifier (I$_K$) current and loss of total intracellular ...K$^+$. This I$_K$ augmentation was not seen in neurons undergoing excitotoxic necrosis or in older neurons resistant to staurosporine-induced apoptosis. Attenuating outward K$^+$ current with tetraethylammonium or elevated extracellular K$^+$, but not blockers of Ca$^{2+}$, Cl$^-$, or other K$^+$ channels, reduced apoptosis, even if associated increases in intracellular Ca$^{2+}$ concentration were prevented. Furthermore, exposure to the K$^+$ ionophore valinomycin or the K$^+$-channel opener cromakalim induced apoptosis. Enhanced K$^+$ efflux may mediate certain forms of neuronal apoptosis.
A new naphthalene-2(3
H
)-one, yuzhenone (
1
), was isolated from the seed shells of
Michelia champaca
L. (Magnoliaceae). The structure of the new naphthalene-2(3
H
)-one derivative was elucidated by ...chemical and physical evidence.
A new ketone, volubilisone (
1
), was isolated from the seed shells of
Plukenetia volubilis
L. (Euphorbiaceae). The structure of the new 4-hydroxy-4-methoxybutan-2-one derivative was elucidated by ...chemical and physical evidence.
A practical monthly optimization model, called SISOPT, is developed for the management and operations of the Brazilian hydropower system. The system, one of the largest in the world, consists of 75 ...hydropower plants with an installed capacity of 69,375 MW, producing 92% of the nation's electrical power. The system size and nonlinearity pose a real challenge to the modelers. The basic model is formulated in nonlinear programming (NLP). The NLP model is the most general formulation and provides a foundation for analysis by other methods. The formulated NLP model was first linearized by two different linearization techniques and solved by linear programming (LP). A comparative analysis was made of the results obtained from the linearized and the NLP models. The results show that the simplest linearized model (referred to as the LP model) without iteration is suitable for planning purposes. For example, the LP model could be used in system capacity expansion studies or to explore various design parameters in connection with feasibility studies, where details in storage variation are not as important as the power production. With a good initial policy provided by the LP model, the successive linear programming (SLP) model produced excellent results with fast convergence. The NLP model, the most complex and accurate model in the suite, is particularly suited for setting up guidelines for real-time operations using inflow forecast with frequent updating. The performance of the NLP model was checked against the historical operational records, and the comparison yields indications of superior performance.
Purpose We have noted that inadequate drug delivery to tumor cells is a major cause of failed intravesical therapy for nonmuscle invading bladder cancer, partly due to the dilution of drug ...concentration by urine production during treatment. To address this problem we developed gelatin nanoparticles of paclitaxel designed to yield constant drug concentrations. The hypothesis that a constant, therapeutic concentration in urine, bladder tissue and tumors can be attained was evaluated in dogs. Materials and Methods We studied drug release from paclitaxel gelatin nanoparticles in culture medium in vitro. In vivo studies were performed in tumor-free dogs and in pet dogs with naturally occurring transitional cell carcinoma, in which the pharmacokinetics of paclitaxel gelatin nanoparticles were determined in plasma, urine and tumors. Results Paclitaxel release from paclitaxel gelatin nanoparticles in vitro and in vivo was rate limited by the drug solubility in aqueous medium. This property yielded constant drug concentrations independent of changes in urine volume during the 2-hour treatment. Intravesical paclitaxel gelatin nanoparticles showed low systemic absorption, and favorable bladder tissue/tumor targeting and retention properties with pharmacologically active concentrations retained in tumors for at least 1 week. Conclusions Constant drug release from paclitaxel gelatin nanoparticles may overcome the problem of drug dilution by newly produced urine and the sustained drug levels in tumors may decrease treatment frequency.
While aberrant JAK/STAT signaling is crucial to the development of gastric cancer (GC), its effects on epigenetic alterations of its transcriptional targets remains unclear. In this study, by ...expression microarrays coupled with bioinformatic analyses, we identified a putative STAT3 target gene, NR4A3 that was downregulated in MKN28 GC daughter cells overexpressing a constitutively activated STAT3 mutant (S16), as compared to an empty vector control (C9). Bisulphite pyrosequencing and demethylation treatment showed that NR4A3 was epigenetically silenced by promoter DNA methylation in S16 and other GC cell lines including AGS cells, showing constitutive activation of STAT3. Subsequent experiments revealed that NR4A3 promoter binding by STAT3 might repress its transcription. Long-term depletion of STAT3 derepressed NR4A3 expression, by promoter demethylation, in AGS GC cells. NR4A3 re-expression in GC cell lines sensitized the cells to cisplatin, and inhibited tumor growth in vitro and in vivo, in an animal model. Clinically, GC patients with high NR4A3 methylation, or lower NR4A3 protein expression, had significantly shorter overall survival. Intriguingly, STAT3 activation significantly associated only with NR4A3 methylation in low-stage patient samples. Taken together, aberrant JAK/STAT3 signaling epigenetically silences a potential tumor suppressor, NR4A3, in gastric cancer, plausibly representing a reliable biomarker for gastric cancer prognosis.
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