Computational and in vitro analyses on synergistic effects of paclitaxel and thymoquinone in suppressing invasive breast cancer cells.

BACKGROUND: In the present experiment, we evaluated the impact of thymoquinone (TQ) and paclitaxel (PTX) treatment on MDA-MB-231 cell line growth inhibition via controlling apoptosis/autophagy. MATERIALS AND RESULTS: MDA-MB-231cells were exposed to PTX (0, 25, 50, 75, and 100 nM), TQ (0, 25, 50, 75, and 100 µM), and combinations for 48 h. After the MTT assessment, dose-response curves and IC50 values were calculated, and the combination synergism was evaluated using the Compusyn software. Following the treatment with PTX, TQ, and combinations at IC50 doses, the expression of apoptosis and autophagy genes was assessed in cells. The GraphPad Prism program was used to analyze the data, and Tukey's test at p < 0.05 was then run. PTX, TQ, and their combinations inhibited MDA-MB-231cell proliferation and viability dose-dependently. TQ reduced the effective concentration (IC50) of PTX in co-treatment groups. PTX and TQ showed antagonistic effects when cell proliferation declined above 70%. Antagonistic effects shifted into additive and synergistic effects upon increasing PTX concentration, indicated by diminished cell proliferation below 70%. PTX-TQ co-treatment significantly enhanced P53 and BAX expression while reducing Bcl-2 expression. Also, their combination increased Beclin-1, ATG-5, and ATG-7 expression in treated cells. CONCLUSION: Effective concentrations of TQ and PTX had synergic effects and inhibited breast cancer cells via prompting apoptosis and autophagy in vitro.

Investigating executive functioning and episodic future thinking in Iranian women with breast cancer.

BACKGROUND: This study examined executive functioning and episodic future thinking among Iranian women with breast cancer. METHOD: We recruited 40 healthy female community volunteers and 80 females with breast cancer (either currently undergoing chemotherapy n = 40 or not undergoing chemotherapy n = 40). Participants were assessed using cognitive tasks that assessed executive functioning and episodic future thinking and a measure of cancer-related fatigue. RESULTS: Both cancer groups had poorer performance than controls on all measures of executive functioning and episodic future thinking. Those undergoing chemotherapy had poorer performance on all measures of executive functioning than those not undergoing chemotherapy. Cross-sectional mediation analyses revealed cancer-related fatigue had a significant mediator role between cancer group and executive functioning and episodic future thinking. CONCLUSION: Those with breast cancer, particularly those undergoing chemotherapy, may be experiencing cognitive difficulties. These cognitive concerns should be considered by health teams as addressing these impairments may assist in improving quality of life and treatment adherence.

Enhancing cognitive flexibility and working memory in individuals with mild cognitive impairment: Exploring the impact of virtual reality on daily life activities.

Mild Cognitive Impairment (MCI) serving as a transitional stage between normal aging and dementia. This study aimed to explore the impact of virtual reality (VR) on enhancing cognitive flexibility, working memory, and daily life activities. Forty participants diagnosed with MCI were randomly assigned to either an intervention group (N = 20) or a control group (N = 20). Evaluations were at baseline, post-training, and three months post-training using various cognitive assessment tools. Results showed that the VR-based cognitive rehabilitation significantly improved instrumental activities of daily living performance, visual and verbal working memory, and reduced anxiety and depression symptoms. While cognitive flexibility did not exhibit significant improvement, these findings highlight VR interventions as a potential avenue for improving cognitive and functional aspects, and alleviating psychological symptoms in individuals with MCI. Further research with larger sample sizes and extended follow-up periods is recommended to establish the long-term effectiveness of such interventions.

Photon approach to diffraction, interference, optical coherence, and image formation.

When a parallel beam of light illuminates an aperture, the uncertainty principles require associating probability amplitude to a photon at each point of the aperture. Superposition of the amplitudes at the observation point behind the aperture, determines the probability that the photon strikes the point. In this paper, we show that this "photon approach" explains several optical concepts. The approach is applied to study the diffraction from a single slit, double slit, and transmission phase step. Then, we apply it to explain the diffraction from a bi-prism and a Michelson's interferometer, and show that the photon approach to the appearance of the interference fringes is more reasonable than the wave approach. We deduce the coherence behavior of light from the uncertainty principles, and finally, we use the photon approach to extract the ray optics laws and image formation formulae.

Simple high-resolution 3D microscopy by a dielectric microsphere: a proof of concept.

We present a simple high-resolution approach for 3D and quantitative phase imaging (QPI). Our method makes the most of a glass microsphere (MS) for microscopy and a glass plate for lateral shearing self-referencing interferometry. The single MS serves all the functions of a microscope objective (MO) in digital holographic microscopy (DHM) while offering the advantages of compactness, lightness, and affordability. A proof-of-concept experiment is performed on a standard diffraction grating, and various effective parameters on the imaging performance are investigated. The results are validated by atomic force microscopy and Mirau-DHM, and 3D morphometric information of the sample under inspection is obtained. The technique is then applied for 3D quantitative measurement and visualization of a human red blood cell, proving the principle of our easy-to-implement and vibration-immune arrangement for high-contrast label-free QPI of biological samples, and its utility in cell morphology, identification, and classification.

Microsphere-assisted super-resolved hyperspectral microscopy.

Hyperspectral microscopy (HSM) combines conventional microscopy with basic hyperspectral imaging and results in 3D microscopic spatio-spectral information. The combination comes along with a variety of applications, such as detection and classification of different material properties through spectral fingerprints, which otherwise cannot be detected with a color camera alone. However, similar to other microscopies, the resolution of HSM is limited by diffraction. In recent years microsphere (MS)-assisted microscopy has attracted intensive attention for resolution enhancement. Here, we extend the MS idea into HSM. We show that MS-HSM reveals extra hyperspectral information about the specimen which is lost without it. Moreover, the insertion of MS results in super-resolved images. The resolution enhancement and obtaining the extra hyperspectral information can be tuned by the MS size.

Digital holographic microscopy of spiropyran-based dynamic materials.

Spiropyran (SP)-based dynamic materials undergo structural changes in response to external stimuli. In this paper, we show that digital holographic microscopy (DHM) is an effective candidate for characterisation of SPs (embedded in polymer matrices) and for monitoring of their dynamical changes. The polymer matrices are polylactic acid (PLA) and poly(methyl methacrylate) (PMMA) films, which are decorated with SPs and immobilised on graphene quantum dots (GQDs). GQDs are modified by benzylamines prior to the loading of SP species because of the enhancement of hydrophobic characteristics. UV irradiation is used as the external stimulus and the dynamical changes of the samples before and after UV irradiation are measured. DHM is arranged on a novel self-referencing setup, which substantially reduces the sensitivity of DHM to environmental vibrations. Morphometric information for characterisation of the samples is obtained by analysis of the recorded digital holograms. The experimental results demonstrate the potential of the presented technique to serve as an alternative technique for surface measurement methodologies such as atomic force microscope and stylus profiler for surface characterisation of similar materials.

Feasibility and acceptability of written exposure therapy in addressing posttraumatic stress disorder in Iranian patients with breast cancer.

OBJECTIVE: This study examined the feasibility and acceptability of written exposure therapy (WET) in reducing symptoms of posttraumatic stress disorder (PTSD) in Iranian women with breast cancer. Secondary aims included examining the influence of WET on quality of life (QoL), overgeneral memory and illness perceptions. METHOD: Forty-six females with breast cancer and clinical symptoms of PTSD referred to the Razi Hospital in Rasht, Iran were randomly assigned to either WET (n = 23) or control (n = 23) groups. WET is a 5-session low-intensity exposure-based intervention for treating PTSD. The control group had no additional contact. Measures assessing PTSD, illness perceptions, overgeneral memory, and QoL were administered at baseline, post-intervention and 3-month follow-up. RESULTS: Acceptability of WET was high; all participants completed all WET sessions. At post-intervention, 95.65% of the WET group met criteria for reliable change and 100% met criteria for minimal clinically important difference (MCID) and clinically significant change in PTSD symptom improvement. At follow-up, all WET participants met criteria for reliable change, MCID and clinically significant change in PTSD symptom improvement. No participants in the control group met reliable change, MCID or clinically significant change. The WET group had improved QoL and memory specificity and decreased threatening illness perceptions at post-intervention and follow-up when compared to controls. CONCLUSION: WET may be a useful intervention for use with breast cancer patients with PTSD symptoms and may be an important adjunct to medical and pharmacological treatments, particularly in low- and middle-income countries. This study indicates further research in this area is warranted.

Cognitive rehabilitation for improving cognitive functions and reducing the severity of depressive symptoms in adult patients with Major Depressive Disorder: a systematic review and meta-analysis of randomized controlled clinical trials.

INTRODUCTION: Nearly 40% of patients with Major Depressive Disorder (MDD) have been found to experience cognitive impairment in at least one domain. Cognitive impairment associated with MDD is disproportionately represented in patients that have not fully returned to psychosocial functioning. As awareness regarding cognitive dysfunction in MDD patients grows, so does the interest in developing newer treatments that specifically address these deficits. METHOD: In the present study, we conduct a systematic review of controlled randomized clinical trials that used cognitive training and remediation interventions for improving cognitive functions and reducing symptom severity in adult patients with MDD. We selected studies published before March 2022 using search databases including PubMed, ScienceDirect, Scopus, and Google scholar. For conducting the meta-analysis, standard differences in means with the random effect model and with a 95% confidence interval of change in outcome measures from baseline to post-intervention between the cognitive rehabilitation and the control groups were calculated. RESULTS: The database search resulted in identifying 756 studies of interest, which ultimately 15 studies with 410 participants in the cognitive rehabilitation group and 339 participants in the control group were included. The meta-analysis of the data extracted from these studies, shows a moderate and significant effect on the executive function (d = 0.59 (95% CI, 0.25 to 0.93) p-value = 0.001, I2 = 15.2%), verbal learning (d = 0.45 (95% CI, 0.12 to 0.78) p-value = 0.007, I2 = 0.00%), and working memory (d = 0.41 (95% CI, 0.18 to 0.64) p-value < 0.001, I2 = 33%) of MDD patients. Although, there were no significant difference between intervention and control group in attention (d = 0.32 (95% CI, -0.01 to 0.66) p-value = 0.058, I2 = 0.00%) or depressive symptoms. CONCLUSION: This systematic review and meta-analysis indicate that cognitive rehabilitation is an effective intervention for the executive function, verbal learning, and working memory of MDD patients. Due to the importance of these neuropsychological deficits in day-to-day life and the core symptoms of MDD, cognitive rehabilitation should be considered an important part of treating MDD. Further research in this area and concentrated on these particular deficits is warranted.

Surgical anatomic findings of sphenoid sinus in 1009 Iranian patients with pituitary adenoma undergoing endoscopic transsphenoidal surgery.

OBJECTIVE: The most common surgical technique for the management of pituitary adenomas is the endoscopic endonasal transsphenoidal approach (EEA). preoperative neuroimaging along with detecting surgical landmarks of the sphenoid sinus during surgery is important for making a successful operation. METHOD: This study includes 1009 patients with pituitary adenomas who underwent EEA between 2013 and 2020. We evaluated the anatomical features of the sphenoid sinus through a panel of items obtained from imaging and intra-operative findings. RESULTS: Our result includes 57.38% nonfunctional, 8.42% cushing, 12.39% prolactinoma, and 21.8% acromegaly patients who had undergone endoscopic endonasal transsphenoidal surgery. The mean age of the patients was 45 with a male to female ratio of 1.2:1. Sellar sphenoid type was the most common (91.8%) with only 12% symmetrical inter sphenoid septa, Internal carotid artery dehiscence was found in 1.7% of the cases. Apoplexy was present in 6.3% of patients, which was found more prevalent in nonfunctional adenomas (9.67%, Odds ratio: 4.85, 95% CI 2.24-11.79) and further investigation revealed a significant association between apoplexy and sphenoid mucosal edema and hemorrhage (Odds ratio: 43.0, 95% CI 22.50-84.26), and between apoplexy and cystic lesions (OR = 4.14, 95% CI 1.87-8.45, P-value < 0.0001). Acromegaly is associated with the increased number of lateral recces (Odds ratio: 11.41, 95% CI 7.54-17.52), septation of the sphenoid sinus (Marginal mean: 3.92, 95% CI 3.69-4.14), edematous sinonasal mucosa (Odds ratio: 6.7; 95% CI 4.46-10.08), and higher bony (OR: 4.81, 95% CI 2.60-8.97, P-value < 0.001) and cavernous (OR: 1.7, 95% CI 1.13-2.46, P-value < 0.01) invasion. CONCLUSION: The present study provides anatomical data about the sphenoid sinus and its adjacent vital structures with adenomal specific changes that are necessary to prevent complications during endoscopic advanced transsphenoidal surgery.

Transitional self-disappear: the journey of cancer survivors to self re-coherence in a Middle East society.

PURPOSE: People who experience cancer often face serious and unpleasant challenges in understanding their past, present, and future. They think they have lost their lifetime, agency, and interpersonal relationships, and no longer know their bodies. These experiences can change survivors' perceptions of themselves. Therefore, the present study aimed to develop a deep theoretical understanding of the change of self in cancer survivors. METHODS: Semi-structured interviews were used to collect data. Interviews were conducted with 17 cancer survivors, 2 oncologists, and 2 family members of survivors. In this study, grounded theory methodology was used to explore the process of understanding and experiencing "self" in cancer survivors. RESULTS: The present study generated a model about the change of self, with the main concept called "transitional self-disappear," which is understandable based on the concepts of self-disruption (temporal disruption, highlighted body, interference in the agency, individual-self disruption, over-differentiation, relational self-disruption, and painful emotional experiences), self-reconstruction strategy, and quality of self-coherence, and occurs in the context of the cancer-based socio-cultural experiences and individual-environmental preparedness. CONCLUSION: This model illuminated the complex paths and roads of the survivors' journey from self-disappear to self reconstruction/re-coherence. A healthier experience of this journey can be facilitated by the transcendence of the "self" conceptualized in the past, and the promotion of specific (cancer-based socio-cultural experiences) and general (individual-environmental preparedness) conditions.

Digital holographic microscopy for real-time investigation of 3D microstructural dynamics of starch-kefiran-based nanocomposite.

Investigating real-time phenomena in bio-polymers has received much attention because of their increasing demands in polymer substitution. The 3D morphometry of polymer surfaces may be very impactful in such studies. Here, digital holographic microscopy (DHM) is applied for quantitative measurement of the rare morphological changes of UV-A and UV-C exposed nanocomposites during their incubation with excess water. By reconstructing the recorded successive digital holograms, the time evolution of the swelled regions of the samples is derived. Our results clearly show that the higher water swelling of UV-A irradiated starch/kefiran/ZnO may be attributed to its higher hydrophilicity.

Correlation of Serum Adipolin with Epicardial Fat Thickness and Severity of Coronary Artery Diseases in Acute Myocardial Infarction and Stable Angina Pectoris Patients.

OBJECTIVE: Adipolin/C1q/TNF-related protein-12 is a family of CTRPs highly expressed in adipose tissue with glucose-lowering and anti-inflammatory effects. Various risk factors have been suggested in the incidence of cardiovascular diseases, such as a decrease in anti-inflammatory or an increase in inflammatory factors. The purpose of the present study was to investigate the correlation of adipolin with anthropometric, angiographic, echocardiographic, and biochemical parameters. SUBJECT AND METHODS: A total of 90 patients who were candidates for angiography were included in the study and divided into 3 groups: 30 patients with acute myocardial infarction (AMI), 30 patients with stable angina pectoris (SAP), and 30 subjects as a control group with a history of chest pain but normal angiography. Anthropometric, angiographic, echocardiographic, and biochemical parameters were measured in all subjects. RESULTS: Serum adipolin levels were significantly decreased in patients with AMI compared with the SAP and control groups (p < 0.001 for both). In addition, there was a negative association between serum levels of adipolin and epicardial fat thickness (EFT) and Gensini score in CAD patients. The results of multivariate linear regression analysis revealed that EFT values were independently associated with serum adipolin levels. CONCLUSION: The current study showed an independent association of adipolin with EFT for the first time in patients with AMI. Decreased adipolin levels in patients with AMI may be involved in the process of atherosclerosis, which requires further study.

Microsphere-assisted super-resolved Mueller matrix microscopy.

Mueller matrix microscopy (MMM) is a powerful approach to probe microstructural and optical information of many important specimens (e.g., tissue and bacteria), which otherwise cannot be obtained directly from intensity or spectral images. Achieving high lateral resolution in MMM, similar to other microscopy approaches, remains a challenge. Here, we extend the idea of microsphere (MS) -assisted microscopy into MMM toward resolution-enhanced polarimetric imaging. The goal is achieved by insertion of a transparent MS in the working distance of the imaging microscope objective in the optical train of an MMM system. We experimentally show that an MS close to the sample in MMM may increase the resolution beyond the intrinsic diffraction limit of the system by redirecting the higher spatial frequencies of the sample into the acceptance cone. In order to be a case in point, the experiment is conducted on a standard holographic diffraction grating with 1 µm line-width, which is beyond the diffraction limit of a 10× objective. Two-dimensional images of the Mueller matrix and some of the widely used quantitative polarimetric parameters of the sample are calculated and compared in the two cases before and after insertion of MS. The proposed arrangement is easy to implement and has the potential to serve as a high-resolution polarimetric microscope for visualizing the polarization characteristics of the microscopic objects.

Design, synthesis, in vivo and in vitro studies of 1,2,3,4-tetrahydro-9H-carbazole derivatives, highly selective and potent butyrylcholinesterase inhibitors.

Inhibition of butyrylcholinesterase (BChE) might be a useful therapeutic target for Alzheimer's disease (AD). A new series of 1,2,3,4-tetrahydro-9H-carbazole derivatives were designed synthesized and evaluated as BChE inhibitors. While all of the derivatives have shown for AChE IC50 values below the detectable limit (> 100 µM), they were selective potent BChE inhibitors. 1-(2-(6-fluoro-1,2,3,4-tetrahydro-9H-carbazole-9-yl)ethyl)piperidin-1-ium chloride (15 g) had the most potent anti-BChE activity (IC50 value = 0.11 µM), the highest BChE selectivity and mixed-type inhibition. Pharmacokinetic properties were accordant to Lipinski rule and compound 15g demonstrated neuroprotective and inhibition of ß-secretase (BACE1) activities. Furthermore, in vivo study of compound 15g in Morris water maze task has confirmed memory improvement in scopolamine-induced impairment. All results suggest that new sets of potent selective inhibitors of BChE have a therapeutic potential for the treatment of AD. A new series of 1,2,3,4-tetrahydro-9H-carbazole derivatives were designed synthesized and evaluated as BChE inhibitors. While all of the derivatives have shown for AChE IC50 values below the detectable limit, they were selective potent BChE inhibitors. Compound 15g had the most potent anti-BChE activity. All results suggest that new sets of potent selective inhibitors of BChE have a therapeutic potential for the treatment of AD.

Gallic acid mitigates diclofenac-induced liver toxicity by modulating oxidative stress and suppressing IL-1ß gene expression in male rats.

CONTEXT: Diclofenac (DIC) is an NSAID and consumption of this drug creates side effects such as liver injury. Gallic acid (GA), a natural component of many plants, is used as an antioxidant agent. OBJECTIVE: This study assesses the hepatoprotective effects of GA in the rat model of DIC-induced liver toxicity. MATERIALS AND METHODS: In this research, the male Wistar rats were separated into five groups (n = 6). Group 1, control, received normal saline (1 mL/kg bw, i.p.); Group 2 received DIC-only (50 mg/kg bw, i.p.); Groups 3, received DIC (50 mg/kg bw, i.p.) plus silymarin (100 mg/kg bw, po), groups 4 and 5 received DIC (50 mg/kg bw, i.p.) plus GA (50 and 100 mg/kg, po, respectively). RESULTS: The data demonstrated that the liver levels of the GSH, GPx, SOD, and CAT significantly reduced and the levels of the serum protein carbonyl, AST, ALP, ALT, total bilirubin, MDA, serum IL-1ß, and the liver IL-1ß gene expression were remarkably increased in the second group compared to control group. On the other hand, treatment with GA led to a significant elevation in GSH, GPx, SOD, CAT, and a significant decrease in protein carbonyl, AST, ALP, ALT, total bilirubin, MDA, serum IL-1ß, and gene expression of IL-1ß in comparison with the second group. Histological changes were also ameliorated by GA oral administration. Discussion and Conclusions: The data show that the oral administration of GA could alleviate the noxious effects of DIC on the antioxidant defense system and liver tissue.

Targeting autophagy in cardiac ischemia/reperfusion injury: A novel therapeutic strategy.

Acute myocardial infarction (AMI) is one of the leading causes of morbidity worldwide. Myocardial reperfusion is known as an effective therapeutic choice against AMI. However, reperfusion of blood flow induces ischemia/reperfusion (I/R) injury through different complex processes including ion accumulation, disruption of mitochondrial membrane potential, the formation of reactive oxygen species, and so forth. One of the processes that gets activated in response to I/R injury is autophagy. Indeed, autophagy acts as a "double-edged sword" in the pathology of myocardial I/R injury and there is a controversy about autophagy being beneficial or detrimental. On the basis of the autophagy effect and regulation on myocardial I/R injury, many studies targeted it as a therapeutic strategy. In this review, we discuss the role of autophagy in I/R injury and its targeting as a therapeutic strategy.

New classes of carbazoles as potential multi-functional anti-Alzheimer's agents.

Multi-Target approach is particularly promising way to drug discovery against Alzheimer's disease. In the present study, we synthesized a series of compounds comprising the carbazole backbone linked to the benzyl piperazine, benzyl piperidine, pyridine, quinoline, or isoquinoline moiety through an aliphatic linker and evaluated as cholinesterase inhibitors. The synthesized compounds showed IC50 values of 0.11-36.5 µM and 0.02-98.6 µM against acetyl- and butyrylcholinesterase (AChE and BuChE), respectively. The ligand-protein docking simulations and kinetic studies revealed that compound 3s could bind effectively to the peripheral anionic binding site (PAS) and anionic site of the enzyme with mixed-type inhibition. Compound 3s was the most potent compound against AChE and BuChE and showed acceptable inhibition potency for self- and AChE-induced Aß1-42 aggregation. Moreover, compound 3s could significantly protect PC12 cells against H2O2-induced toxicity. The results suggested that the compounds 3s could be considered as a promising multi-functional agent for further drug discovery development against Alzheimer's disease.

Design, synthesis and anti-Alzheimer's activity of novel 1,2,3-triazole-chromenone carboxamide derivatives.

Alzheimer's disease (AD) is a well-known neurodegenerative disorder affecting millions of old people worldwide and the corresponding epidemiological data highlights the significance of the disease. As AD is a multifactorial illness, various single-target directed drugs that have reached clinical trials have failed. Therefore, various factors associated with outset of AD have been considered in targeted drug discovery and development. In this work, a wide range of 1,2,3-triazole-chromenone carboxamides were designed, synthesized, and evaluated for their cholinesterase inhibitory activity. Among them, N-(1-benzylpiperidin-4-yl)-7-((1-(3,4-dimethylbenzyl)-1H-1,2,3-triazol-4-yl)methoxy)-2-oxo-2H-chromene-3-carboxamide (11b) showed the best acetylcholinesterase inhibitory activity (IC50 = 1.80 µM), however, it was inactive toward butyrylcholinesterase. It should be noted that compound 11b was evaluated for its BACE1 inhibitory activity and calculated IC50 = 21.13 µM confirmed desired inhibitory activity. Also, this compound revealed satisfactory neuroprotective effect against H2O2-induced cell death in PC12 neurons at 50 µM as well as metal chelating ability toward Fe2+, Cu2+, and Zn2+ ions.

Speckle pattern analysis of crumpled papers.

In this paper, we show that laser speckle analysis (LSA) can provide valuable information about the structure of crumpled thin sheets. Crumpling and folding of slender objects are present in several phenomena and in various ranges of size, e.g., paper compaction, cortical folding in brains, DNA packing in viral capsids, and flower buds, to name a few. The analysis of laser speckles, both numerical and graphical, is a source of information about the activity of biological or non-biological materials, and the development of digital electronics, which brought the ease of image processing, has opened new perspectives for a spectrum of LSA applications. LSA is applied on randomly crumpled and one-, two-, and three-times folded papers, and appreciable differences in LSA parameters are observed. The methodology can be applied for easy-to-implement quantitative assessment of similar phenomena and samples.