Background: Fewer than 6% patients with adenocarcinoma of the pancreas live up to five years after diagnosis. Chemotherapy is currently the standard treatment, however, these tumors often develop drug resistance over time. Agents for increasing the cytotoxic effects of chemotherapy or reducing the cancer cells’ chemo-resistance to the drugs are required to improve treatment outcome. Nuclear factor kappa B (NF-kB), a pro-inflammatory transcription factor, reportedly plays a significant role in the resistance of pancreatic cancer cells to apoptosis-based chemotherapy. This study investigated the effect of aqueous Moringa Oleifera leaf extract on cultured human pancreatic cancer cells - Panc-1, p34, and COLO 357, and whether it can potentiates the effect of cisplatin chemotherapy on these cells. Methods: The effect of Moringa Oleifera leaf extract alone and in combination with cisplatin on the survival of cultured human pancreatic cancer cells was evaluated by XTT-based colorimetric assay. The distribution of Panc-1 cells in the cell cycle following treatment with Moringa leaf extract was evaluated by flow cytometry, and evaluations of protein levels were via immunoblotting. Data of cell survival following combined treatments were analyzed with Calcusyn software. Results: Moringa Oleifera leaf extract inhibited the growth of all pancreatic cell lines tested. This effect was significant in all cells following exposure to ≥0.75 mg/ml of the extract. Exposure of Panc-1 cells to Moringa leaf extract induced an elevation in the sub-G1 cell population of the cell-cycle, and reduced the expression of p65, p-IkBα and IkBα proteins in crude cell extracts. Lastly, Moringa Oleifera leaf extract synergistically enhanced the cytotoxic effect of cisplatin on Panc-1 cells. Conclusion: Moringa Oleifera leaf extract inhibits the growth of pancreatic cancer cells, the cells NF-κB signaling pathway, and increases the efficacy of chemotherapy in human pancreatic cancer cells.

Purpose: Multiple studies have indicated that cyclooxygenase-2 (COX-2) inhibitors may prevent colon cancer, which is one of the leading causes of cancer death in the western world. Recent studies, however, showed that their long-term use may be limited due to cardiovascular toxicity. This study aims to investigate whether curcumin potentiates the growth inhibitory effect of celecoxib, a specific COX-2 inhibitor, in human colon cancer cells. Experimental Design: HT-29 and IEC-18-K-ras (expressing high levels of COX-2), Caco-2 (expressing low level of COX-2), and SW-480 (no expression of COX-2) cell lines were exposed to different concentrations of celecoxib (0-50 μmol/L), curcumin (0-20 μmol/L), and their combination. COX-2 activity was assessed by measuring prostaglandin E₂ production by enzyme-linked immunoassay. COX-2 mRNA levels were assessed by reverse transcription-PCR. Results: Exposure to curcumin (10-15 μmol/L) and physiologic doses of celecoxib (5 μmol/L) resulted in a synergistic inhibitory effect on cell growth. Growth inhibition was associated with inhibition of proliferation and induction of apoptosis. Curcumin augmented celecoxib inhibition of prostaglandin E₂ synthesis. The drugs synergistically down-regulated COX-2 mRNA expression. Western blot analysis showed that the level of COX-1 was not altered by treatment with celecoxib, curcumin, or their combination. Conclusions: Curcumin potentiates the growth inhibitory effect of celecoxib by shifting the dose-response curve to the left. The synergistic growth inhibitory effect was mediated through a mechanism that probably involves inhibition of the COX-2 pathway and may involve other non–COX-2 pathways. This synergistic effect is clinically important because it can be achieved in the serum of patients receiving standard anti-inflammatory or antineoplastic dosages of celecoxib.

Objective: The COVID-19 pandemic has had a major impact on teachers professional and personal lives. Our primary aim was to assess the effect of a blended Inquiry-Based Stress Reduction (IBSR), an emerging mindfulness and cognitive reframing intervention on teacher’s well-being. Our secondary aims were to assess the effect of IBSR on resilience, burnout, mindfulness, and stress among teachers during the COVID-19 pandemic. Methods: The study was a prospective controlled trial with an intervention group (N = 35) and a comparison control group (N = 32). The intervention took place in the Jerusalem District throughout the school year from November 2019 to May 2020. The sessions were conducted in blended learning that included traditional learning (face-to-face) and online learning. Data was analyzed on an intention-to-treat basis. Results: IBSR blended intervention enhanced the resilience and improved the subjective and psychological well-being of teachers in spite of the breakout of the COVID-19 pandemic and the first lockdown in Israel. Simultaneously the control group suffered from enhanced burnout levels and a decline in psychological and subjective well-being. Conclusions: Implementation of IBSR blended intervention during the school year may benefit teachers’ well-being and ability to flourish, even during stressful events such as the COVID-19 pandemic.

A small but significant proportion of COVID‐19 patients develop life‐threatening cytokine storm. We have developed a new anti‐inflammatory drug, EXO‐CD24, a combination of an immune checkpoint (CD24) and a delivery platform (exosomes). CD24 inhibits the NF‐kB pathway and the production of cytokines/chemokines. EXO‐CD24 discriminates damage‐from pathogen‐associated molecular patterns (DAMPs and PAMPs) therefore does not interfere with viral clearance. EXO‐CD24 was produced and purified from CD24‐expressing 293‐TREx™ cells. Exosomes displaying murine CD24 (mCD24) were also created. EXO‐CD24/mCD24 were characterized and examined, for safety and efficacy, in vitro and in vivo. In a phase Ib/IIa study, 35 patients with moderate–high severity COVID‐19 were recruited and given escalating doses, 10⁸–10¹⁰, of EXO‐CD24 by inhalation, QD, for 5 days. No adverse events related to the drug were observed up to 443–575 days. EXO‐CD24 effectively reduced inflammatory markers and cytokine/chemokine, although randomized studies are required. EXO‐CD24 may be a treatment strategy to suppress the hyper‐inflammatory response in the lungs of COVID‐19 patients and further serve as a therapeutic platform for other pulmonary and systemic diseases characterized by cytokine storm.

Background: Senior centers and other types of clubs provide activities for older adults to address boredom, social isolation, and loneliness. Due to the COVID-19 pandemic, most of these activities have been cancelled. A limited range of web-based activities have been offered as alternatives. However, the effectiveness of these web-based group activities for older adults has scarcely been researched. Objective: We aimed to understand the extent to which web-based activities for older adults provide an adequate substitute for in-person activities. Methods: In this telephone survey, we interviewed 105 older adults in Israel who had been offered the opportunity to participate in web-based activities after routine activities closed due to the COVID-19 pandemic. Of the total sample, 49/105 (46.7%) participated in the activities and 56/105 (53.3%) did not. We inquired about the respondents’ background characteristics, satisfaction with the activities, and reasons for participation or nonparticipation. Results: The respondents who participated in the web-based activities tended to be highly satisfied with at least some of them. They rated the enjoyment derived from the content of the activity as the most important motivator, followed by maintaining a routine and by enjoying the group and the presence of others. Over 50% of the participants (28/49, 57%) wished to continue with the exercise programming after the end of the COVID-19 pandemic, and 41% (20/49) wished to continue with the web-based lectures. Participants were more likely to report partaking in alternative activities than nonparticipants (P=.04). The most common reasons cited by nonparticipants were being unaware of the web-based program (24/56, 43%) despite a notification having been sent to the entire sample, lack of interest in the content (18/56, 32%), and technical issues (13/56, 23%), such as not owning or being able to fully use a computer. Both participants and nonparticipants were interested in a wide range of topics, with many being very particular about the topics they wished to access. Approximately half expressed willingness to pay for access; those who were willing to pay tended to have more years of education (P=.03). Conclusions: Our findings suggest a need for web-based activities for countering boredom and feelings of isolation. The main factors that influence the use, efficacy, and sustainability of online activities are access, motivational and need-fulfilling factors, and whether the activities are sufficiently tailored to individuals’ preferences and abilities. Challenges in substituting in-person services are promoting social relationships that are currently not sufficiently incorporated into most web-based programs, accommodating a wider range of topics, and increasing the accessibility of current programs to older adults, especially those who are homebound, both during and after the COVID-19 pandemic.

Despite great interest in how dynamic fluctuations in psychological states such as mood, social safety, energy, present-focused attention, and burnout impact stress, well-being, and health, most studies examining these constructs use retrospective assessments with relatively long time-lags. Here, we discuss how ecological momentary assessments (EMAs) address methodological issues associated with retrospective reports to help reveal dynamic associations between psychological states at small timescales that are often missed in stress and health research. In addition to helping researchers characterize daily and within-day fluctuations and temporal dynamics between different health-relevant processes, EMAs can elucidate mechanisms through which interventions reduce stress and enhance well-being. EMAs can also be used to identify changes that precede critical health events, which can in turn be used to deliver ecological momentary interventions, or just-in-time interventions, to help prevent such events from occurring. To enable this work, we provide examples of scales and single-item questions used in EMA studies, recommend study designs and statistical approaches that capitalize on EMA data, and discuss limitations of EMA methods. In doing so, we aim to demonstrate how, when used carefully, EMA methods are well poised to greatly advance our understanding of how intrapersonal dynamics affect stress levels, well-being, and human health.