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Formononetin, an isoflavone, is extracted from various medicinal plants and herbs, including the red clover (Trifolium pratense) and Chinese medicinal plant Astragalus membranaceus. Formononetin’s antioxidant and neuroprotective effects underscore its therapeutic use against Alzheimer’s disease. Formononetin has been under intense investigation for the past decade as strong evidence on promoting apoptosis and against proliferation suggests for its use as an anticancer agent against diverse cancers. These anticancer properties are observed in multiple cancer cell models, including breast, colorectal, and prostate cancer. Formononetin also attenuates metastasis and tumor growth in various in vivo studies. The beneficial effects exuded by formononetin can be attributed to its antiproliferative and cell cycle arrest inducing properties. Formononetin regulates various transcription factors and growth-factor-mediated oncogenic pathways, consequently alleviating the possible causes of chronic inflammation that are linked to cancer survival of neoplastic cells and their resistance against chemotherapy. As such, this review summarizes and critically analyzes current evidence on the potential of formononetin for therapy of various malignancies with special emphasis on molecular targets.

Physical exercise and cognitive training have been shown to enhance cognition among older adults. However, few studies have looked at the potential synergetic effects of combining physical and cognitive training in a single study. Prior trials on combined training have led to interesting yet equivocal results. The aim of this study was to examine the effects of combined physical and cognitive interventions on physical fitness and neuropsychological performance in healthy older adults. Seventy-six participants were randomly assigned to one of four training combinations using a 2×2 factorial design. The physical intervention was a mixed aerobic and resistance training program, and the cognitive intervention was a dual-task (DT) training program. Stretching and toning exercises and computer lessons were used as active control conditions. Physical and cognitive measures were collected pre- and postintervention. All groups showed equivalent improvements in measures of functional mobility. The aerobic-strength condition led to larger effect size in lower body strength, independently of cognitive training. All groups showed improved speed of processing and inhibition abilities, but only participants who took part in the DT training, independently of physical training, showed increased task-switching abilities. The level of functional mobility after intervention was significantly associated with task-switching abilities. Combined training did not yield synergetic effects. However, DT training did lead to transfer effects on executive performance in neuropsychological tests. Both aerobic-resistance training and stretching-toning exercises can improve functional mobility in older adults.

Immigrant students face various challenges in high-income countries that can contribute to the decline of their mental well-being upon arrival in their host country. Despite the growing population of these students in several high-income countries, there is inadequate attention given to their mental health needs and their access to mental health services. Thus, this systematic scoping review aimed to identify gaps in existing research relating to the barriers and facilitators associated with access to and use of mental health services in high-income countries. Following the PRISMA-ScR checklist as guidance we systematically searched Ovid Medline, APA PsycInfo, Education Source, CINAHL, Web of Science databases for peer reviewed articles related to barriers and facilitators of mental health service use among immigrant students. We conducted a narrative evidence synthesis to highlight barriers and facilitators to the use of mental health services. Out of the 2407 articles initially found, 47 studies met the inclusion criteria and were considered for this review. The increasing attention towards the mental health concerns of immigrant students and their access to mental health services is evident. However, various barriers like stigma, insufficient knowledge, or adherence to traditional gender roles (such as masculinity) hinder their utilization of these services. On the other hand, factors such as being a woman, having a strong sense of cultural adaptation, or possessing adequate mental health literacy serve as facilitators for accessing mental health services. These students have unique experiences, and their needs are often unmet. To improve their mental health and use of mental health services, it is important to consider the barriers they face and their unique experience in their specific life context and to develop tailored prevention and intervention programs.

Introduction: Many studies have reported that regular physical activity is positively associated with cognitive performance and more selectively with executive functions. However, some studies reported that the association of physical activity on executive performance in younger adults was not as clearly established when compared to studies with older adults. Among the many physiological mechanisms that may influence cognitive functioning, prefrontal (PFC) oxygenation seems to play a major role. The aim of the current study was to assess whether executive function and prefrontal oxygenation are dependent on physical activity levels (active versus inactive) in healthy young males. Methods: Fifty-six healthy young males (22.1 ± 2.4 years) were classified as active (n = 26) or inactive (n = 30) according to the recommendations made by the World Health Organization (WHO) and using the Global Physical Activity Questionnaire (GPAQ). Bilateral PFC oxygenation was assessed using functional near-infrared spectroscopy (fNIRS) during a computerized Stroop task (which included naming, inhibition, and switching conditions). Accuracy (% of correct responses) and reaction times (ms) were used as behavioural indicators of cognitive performances. Changes in oxygenated (∆HbO2) and deoxygenated (∆HHb) hemoglobin were measured to capture neural changes. Several two-way repeated measures ANOVAs (Physical activity level x Stroop conditions) were performed to test the null hypothesis of an absence of interaction between physical activity level and executive performance in prefrontal oxygenation. Results: The analysis revealed an interaction between physical activity level and Stroop conditions on reaction time (p = 0.04; ES = 0.7) in which physical activity level had a moderate effect on reaction time in the switching condition (p = 0.02; ES = 0.8) but not in naming and inhibition conditions. At the neural level, a significant interaction between physical activity level and prefrontal oxygenation was found. Physical activity level had a large effect on ΔHbO2 in the switching condition in the right PFC (p = 0.04; ES = 0.8) and left PFC (p = 0.02; ES = 0.96), but not in other conditions. A large physical activity level effect was also found on ΔHHb in the inhibition condition in the right PFC (p < 0.01; ES = 0.9), but not in the left PFC or other conditions. Conclusion: The results of this cross-sectional study indicate that active young males performed better in executive tasks than their inactive counterparts and had a larger change in oxygenation in the PFC during these most complex conditions.

The cancer microenvironment, or tumor microenvironment (TME), describes the non-cancerous cells present in the tumor, such as fibroblasts, immune cells, and cells that comprise the blood vessels and proteins produced by all of the cells present in the tumor that support the growth of the cancer cells [...]

Background Cancer cells express immunosuppressive molecules, such as programmed death ligands (PD-L)1 and PD-L2, enabling evasion from the host’s immune system. Cancer cells synthesize and secrete acetylcholine (ACh), acting as an autocrine or paracrine hormone to promote their proliferation, differentiation, and migration. Methods We correlated the expression of PD-L1, PD-L2, cholinergic muscarinic receptor 3 (M3R), alpha 7 nicotinic receptor (α7nAChR), and choline acetyltransferase (ChAT) in colorectal cancer (CRC) tissues with the stage of disease, gender, age, risk, and patient survival. The effects of a muscarinic receptor blocker, atropine, and a selective M3R blocker, 4-DAMP, on the expression of immunosuppressive and cholinergic markers were evaluated in human CRC (LIM-2405, HT-29) cells. Results Increased expression of PD-L1, M3R, and ChAT at stages III-IV was associated with a high risk of CRC and poor survival outcomes independent of patients’ gender and age. α7nAChR and PD-L2 were not changed at any CRC stages. Atropine and 4-DAMP suppressed the proliferation and migration of human CRC cells, induced apoptosis, and decreased PD-L1, PD-L2, and M3R expression in CRC cells via inhibition of EGFR and phosphorylation of ERK. Conclusions The expression of immunosuppressive and cholinergic markers may increase the risk of recurrence of CRC. These markers might be used in determining prognosis and treatment regimens for CRC patients. Blocking cholinergic signaling may be a potential therapeutic for CRC through anti-proliferation and anti-migration via inhibition of EGFR and phosphorylation of ERK. These effects allow the immune system to recognize and eliminate cancer cells.

The neuroimaging literature on dual-task gait clearly demonstrates increased prefrontal cortex (PFC) involvement when performing a cognitive task while walking. However, findings from direct comparisons of the cerebral oxygenation patterns of younger (YA) and older (OA) adults during dual-task walking are mixed and it is unclear how YA and OA respond to increasing cognitive load (difficulty) while walking. This functional near infra-red (fNIRS) study examined cerebral oxygenation of YA and OA during self-paced dual-task treadmill walking at two different levels of cognitive load (auditory n-back). Changes in accuracy (%) as well as oxygenated (HbO) and deoxygenated (HbR) hemoglobin were examined. For the HbO and HbR measures, eight regions of interest (ROIs) were assessed: the anterior and posterior dorsolateral and ventrolateral PFC (aDLPFC, pDLPFC, aVLPFC, pVLPFC) in each hemisphere. Nineteen YA ( = 21.83 years) and 14 OA ( = 66.85 years) walked at a self-selected pace while performing auditory 1-back and 2-back tasks. Walking alone (single motor: SM) and performing the cognitive tasks alone (single cognitive: SC) were compared to dual-task walking (DT = SM + SC). In the behavioural data, participants were more accurate in the lowest level of load (1-back) compared to the highest (2-back; < 0.001). YA were more accurate than OA overall ( = 0.009), and particularly in the 2-back task ( = 0.048). In the fNIRS data, both younger and older adults had task effects (SM < DT) in specific ROIs for ΔHbO (three YA, one OA) and ΔHbR (seven YA, eight OA). After controlling for walk speed differences, direct comparisons between YA and OA did not reveal significant age differences, but did reveal a difficulty effect in HbO in the left aDLPFC ( = 0.028) and significant task effects (SM < DT) in HbR for six of the eight ROIs. Findings suggest that YA and OA respond similarly to manipulations of cognitive load when walking on a treadmill at a self-selected pace.

ObjectiveIn order to better understand the barriers that limit the social participation of older people with low vision, the aim of this study was to describe and clarify the factors that shape the social participation of older adults with vision loss.MethodsAs part of a study on rehabilitation access barriers, six qualitative focus groups were conducted in a private room in a hospital, with 21 individuals with low vision (aged 38–92 years) who had or had not accessed low vision services. During the focus groups, participants often spoke of the challenges they faced when interacting with people with ‘normal’ vision; this discussion led to a modification of the interview guide in order to capture barriers to social participation. Focus group discussions were audiotaped and transcribed, and content analysis was conducted.ResultsContent analysis revealed that personal as well as environmental factors influenced the social participation of older adults with low vision. Four themes emerged: 1) experiencing the onset of impairment and degenerating ability, 2) the physical environment, 3) attitudes and responses from others and 4) individual internal attitude and responses during social interactions. Lived and perceived stigma from the perspective of the insider (person living with low vision) interacting with an outsider (person with ‘normal’ vision) and difficult environmental contexts were described as barriers to social participation and optimal functioning.ConclusionAt a personal level, transitioning from an outsider to an insider influenced self-identity and social participation. Further, insiders experiencing stereotypes associated with older adults who are blind had a negative impact on their social participation. Findings highlight the importance of stigma and stereotyping in the lived experience of older adults with low vision. Stigma is persistent, but strategies to reduce stigma will ultimately facilitate the social participation of older adults with low vision.