Antidepressant activity of curcumin: involvement of serotonin and dopamine system

Rationale  Curcumin is a major active principle of Curcuma longa, one of the widely used preparations in the Indian system of medicine. It is known for its diverse biological actions. Objective  The present study was designed to investigate the involvement of monoaminergic system(s) in the antidepressant activity of curcumin and the effect of piperine, a bioavailability enhancer, on the bioavailability and biological effects of curcumin. Methods and observations  Behavioral (forced swim test), biochemical (monoamine oxidase (MAO) enzyme inhibitory activity), and neurochemical (neurotransmitter levels estimation) tests were carried out. Curcumin (10–80 mg/kg, i.p.) dose dependently inhibited the immobility period, increased serotonin (5-hydroxytryptamine, 5-HT) as well as dopamine levels (at higher doses), and inhibited the monoamine oxidase enzymes (both MAO-A and MAO-B, higher doses) in mice. Curcumin (20 mg/kg, i.p.) enhanced the anti-immobility effect of subthreshold doses of various antidepressant drugs like fluoxetine, venlafaxine, or bupropion. However, no significant change in the anti-immobility effect of imipramine and desipramine was observed. Furthermore, combination of subthreshold dose of curcumin and various antidepressant drugs resulted in synergistic increase in serotonin (5-HT) levels as compared to their effect per se. There was no change in the norepinephrine levels. The coadministration of piperine (2.5 mg/kg, i.p.), a bioavailability enhancing agent, with curcumin (20 and 40 mg/kg, i.p.) resulted in potentiation of pharmacological, biochemical, and neurochemical activities. Conclusion  The study provides evidences for mechanism-based antidepressant actions of curcumin. The coadministration of curcumin along with piperine may prove to be a useful and potent natural antidepressant approach in the management of depression.     

A Cross-Sectional Survey Exploring the Impact of the COVID-19 Pandemic on the Cancer Care of Adolescents and Young Adults

We aimed to describe the negative and positive impacts of changes in cancer care delivery due to COVID-19 pandemic for adolescents and young adults (AYAs) in Canada, as well as the correlates of negative impact and their perspectives on optimization of cancer care. We conducted an online, self-administered survey of AYAs with cancer living in Canada between January and February 2021. Multiple logistic regression was used to identify factors associated with a negative impact on cancer care. Of the 805 participants, 173 (21.5%) experienced a negative impact on their cancer care including delays in diagnostic tests (11.9%), cancer treatment (11.4%), and appointments (11.1%). A prior diagnosis of mental or chronic physical health condition, an annual income of <20,000 CAD, ongoing cancer treatment, and province of residence were independently associated with a negative cancer care impact (p-value < 0.05). The majority (n = 767, 95.2%) stated a positive impact of the changes to cancer care delivery, including the implementation of virtual healthcare visits (n = 601, 74.6%). Pandemic-related changes in cancer care delivery have unfavorably and favorably influenced AYAs with cancer. Interventions to support AYAs who are more vulnerable to the adverse effects of the pandemic, and the thoughtful integration of virtual care into cancer care delivery models is essential.     

Disease-related changes in TRPV1 expression and its implications for drug development

The transient receptor potential vanilloid 1 (TRPV1) channel has been a topic of great interest, since its discovery in 1997. It is a homotetrameric non-selective cation channel predominantly expressed in a population of sensory neurons and its involvement in different modalities of pain has been extensively studied. However, TRPV1 has also been shown to be expressed in non-sensory neurons and non-neuronal cells. TRPV1 is considered as a potential target for drug development, based on its tissue distribution and its role in physiological functions. Here, we summarize the evidences for disease-related alterations in TRPV1 expression and function and review the current perspectives for the therapeutic potential of TRPV1 agonists and antagonists in the treatment of a wide range of diseases.     

Hemoglobin degradation in human erythrocytes with long-duration near-infrared laser exposure in Raman optical tweezers

Near-infrared laser (785-nm)-excited Raman spectra from a red blood cell, optically trapped using the same laser beam, show significant changes as a function of trapping duration even at trapping power level of a few milliwatts. These changes in the Raman spectra and the bright-field images of the trapped cell, which show a gradual accumulation of the cell mass at the trap focus, suggest photoinduced aggregation of intracellular heme. The possible role of photoinduced protein denaturation and hemichrome formation in the observed aggregation of heme is discussed.     

Metastatic cutaneous squamous cell carcinoma shows frequent deletion in the protein tyrosine phosphatase receptor Type D gene

Cutaneous squamous cell carcinoma (cSCC) is the second most common form of nonmelanoma skin cancer (NMSC), and its incidence is increasing rapidly. Metastatic cSCC accounts for the majority of deaths associated with NMSC, but the genetic basis for cSCC progression remains poorly understood. A previous study identified small deletions (typically <1 Mb) in the protein tyrosine phosphatase receptor Type D (PTPRD) gene that segregated with more aggressive cSCC. To investigate the apparent association between deletion within PTPRD and cSCC metastasis, a series of 74 formalin-fixed paraffin-embedded tumors from 31 patients was analyzed using a custom Illumina 384 SNP microarray. Deletions were found in 37% of patients with metastatic cSCC and were strongly associated with metastatic tumors when compared to those that had not metastasized (p = 0.007). Subsequent mutation analysis revealed a higher mutation rate for PTPRD than has been reported in any other cancer type, with 37% of tumors harboring a somatic mutation. Conversely, bisulfite sequencing showed that methylation was not a mechanism of PTPRD disruption in cSCC. This is the first report to observe an association between deletion within PTPRD and metastatic disease and highlights the potential use of these deletions as a diagnostic biomarker for tumor progression. Combined with the high mutation rate observed in our study, PTPRD is one of the most commonly altered genes in cSCC and warrants further investigation to determine its significance for metastasis in other tumor types.     

Can diffusion-weighted imaging distinguish between benign and malignant pediatric liver tumors?

Background

There are limited data on utility of diffusion-weighted imaging (DWI) in the evaluation of pediatric liver lesions.

Objective

To determine whether qualitative and quantitative DWI can be used to differentiate benign and malignant pediatric liver lesions.

Materials and methods

We retrospectively reviewed MRIs in children with focal liver lesions to qualitatively evaluate lesions noting diffusion restriction, T2 shine-through, increased diffusion, hypointensity on DWI and apparent diffusion coefficient (ADC) maps, and intermediate signal on both, and to measure ADC values. Pathology confirmation or a combination of clinical, laboratory and imaging features, and follow-up was used to determine final diagnosis.

Results

We included 112 focal hepatic lesions in 89 children (median age 11.5 years, 51 female), of which 92 lesions were benign and 20 malignant. Interobserver agreement was almost perfect for both qualitative (kappa 0.8735) and quantitative (intraclass correlation coefficient [ICC] 0.96) diffusion assessment. All malignant lesions showed diffusion restriction. Most benign lesions other than abscesses were not restricted. There was significant association of qualitative restriction with malignancy and non-restriction with benignancy (Fisher exact test P<0.0001). Mean normalized ADC values of malignant lesions (1.23x10^?3 mm²/s) were lower than benign lesions (1.62x10^?3 mm²/s; Student’s t-test, P<0.015). However, there was significant overlap of ADC between benign and malignant lesions, with wide range for each diagnosis. Receiver operating characteristic (ROC) analysis revealed an area under the curve (AUC) of 0.63 for predicting malignancy using an ADC cut-off value of ≤1.20x10^?3 mm²/s, yielding a sensitivity of 78% and a specificity of 54% for differentiating malignant from benign lesions.

Conclusion

Qualitative diffusion restriction in pediatric liver lesions is a good predictor of malignancy and can help to differentiate between benign and malignant lesions, in conjunction with conventional MR sequences. Even though malignant lesions demonstrated significantly lower ADC values than benign lesions, the use of quantitative diffusion remains limited in its utility for distinguishing them because of the significant overlap and wide ranges of ADC values.