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ABSTRACT Background Colorectal cancer (CRC) is a commonly diagnosed malignancy with significant mortality rates worldwide. The identification of robust prognostic biomarkers for prediction of survival outcomes and recurrence can aid disease management and improve patients' quality of living. Aim This study aimed to investigate the prognostic value of cadherin 17 (CDH17) tissue expression in CRC patients by utilizing a standardized automated immunohistochemistry (IHC) platform integrated with a digitalized scoring system. Methods and Results IHC was conducted to assess CDH17 expression on tumor tissues obtained from 150 retrospective CRC cases. A computer‐assisted imaging analysis was performed to quantify CDH17 tissue expression using an IHC scoring algorithm known as the Membrane (M) Score. The relationship between CDH17 M Score and clinicopathological factors such as TNM staging, distant metastasis, and recurrence status was analyzed. The prognostic value of CDH17 M Score was determined by Kaplan–Meier curves and Cox regression analysis for overall survival (OS) and recurrence‐free survival (RFS). Comparison of M Score and pathologist visual scoring was made to assess the validity of software‐derived IHC scoring. CDH17 expression, as measured by M Score, was found to be significantly increased in tumor tissues compared to adjacent normal tissues, and its expression is associated with advanced staging and distant metastasis (normal vs. tumor, p = 0.0011; Stages IV vs. I–III, p

Objective(s): Neuroinflammation and microglial activation are pathological features in central nervous system disorders. Excess levels of reactive oxygen species (ROS) and pro-inflammatory cytokines have been implicated in exacerbation of neuronal damage during chronic activation of microglial cells. Padina australis, a brown macroalga, has been demonstrated to have various pharmacological properties such as anti-neuroinflammatory activity. However, the underlying mechanism mediating the anti-neuroinflammatory potential of P. australis remains poorly understood. We explored the use of Malaysian P. australis in attenuating lipopolysaccharide (LPS)-stimulated neuroinflammation in BV2 microglial cells. Materials and Methods: Fresh specimens of P. australis were freeze-dried and subjected to ethanol extraction. The ethanol extract (PAEE) was evaluated for its protective effects against 1 µg/ml LPS-stimulated neuroinflammation in BV2 microglial cells. Results: LPS reduced the viability of BV2 microglia cells and increased the levels of nitric oxide (NO), prostaglandin E2 (PGE2), intracellular reactive oxygen species (ROS), inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6). However, the neuroinflammatory response was reversed by 0.5–2.0 mg/ml PAEE in a dose-dependent manner. Analysis of liquid chromatography-mass spectrometry (LC-MS) of PAEE subfractions revealed five compounds; methyl α-eleostearate, ethyl α-eleostearate, niacinamide, stearamide, and linoleic acid. Conclusion: The protective effects of PAEE against LPS-stimulated neuroinflammation in BV2 microglial cells were found to be mediated by the suppression of excess levels of intracellular ROS and pro-inflammatory mediators and cytokines, denoting the protective role of P. australis in combating continuous neuroinflammation. Our findings support the use of P. australis as a possible therapeutic for neuroinflammatory and neurodegenerative diseases.

The ‘neurogenesis hypothesis of depression’ emphasizes the importance of upregulated hippocampal neurogenesis for the efficacy of antidepressant treatment. Neuromodulation is a promising therapeutic method that stimulates neural circuitries to treat neuropsychiatric illnesses. We conducted a scoping review on the neurogenic and antidepressant outcomes of neuromodulation in animal models of depression. PubMed, Web of Science, and PsycInfo were comprehensively searched for full-text English articles from inception to October 5, 2021. Data screening and extraction were conducted independently by two researchers. Seventeen eligible studies were included in this review. The majority of studies used non-invasive neuromodulation (n = 14) and assessed neurogenesis using neural proliferation (n = 16) and differentiation markers (n = 9). Limited reports (n = 2) used neurogenic inhibitors to evaluate the role of neurogenesis on the depressive-like behavioral outcomes. Overall, neuromodulation substantially effectuated both hippocampal cell proliferation and antidepressant-like behavior in animal models of depression, with some providing evidence for enhanced neuronal differentiation and maturation. The proposed neurogenic-related mechanisms mediating the neuromodulation efficacies included neurotrophic processes, anti-apoptotic pathways, and normalization of HPA axis functions. Further research is warranted to explore the role of neuromodulation-induced neurogenic effects on treatment efficacies and to elucidate the underlying molecular mechanisms.

Objective(s): The involvement of tetratricopeptide repeat domain 9A (TTC9A) in anxiety-like behaviors through estrogen action has been reported in female mice, this study further investigated its effects on social anxiety and aggressive behaviors.Materials and sMethods: Using female Ttc9a knockout (Ttc9a-/-) mice, the role of TTC9A in anxiety was investigated in non-social and social environments through home-cage emergence and social interaction tests, respectively, whereas aggressive behaviors were examined under the female intruder test. Results: We observed significant social behavioral deficits with pronounced social and non-social anxiogenic phenotypes in female Ttc9a-/- mice. When tested for aggressive-like behaviors, we found a reduction in offense in Ttc9a-/- animals, suggesting that TTC9A deficiency impairs the offense responses in female mice. Conclusion: Future study investigating mechanisms underlying the social anxiety-like behavioral changes in Ttc9a-/- mice may promote the understanding of social and anxiety disorders.

Background: Given that visual impairment is bi-directionally associated with depression, we examined whether transcorneal electrical stimulation (TES), a non-invasive treatment for visual disorders, can ameliorate depressive symptoms. Objective: The putative antidepressant-like effects of TES and the underlying mechanisms were investigated in an S334ter-line-3 rat model of retinal degeneration and a rat model of chronic unpredictable stress (CUS). Methods: TES was administered daily for 1 week in S334ter-line-3 and CUS rats. The effects of TES on behavioral parameters, plasma corticosterone levels, and different aspects of neuroplasticity, including neurogenesis, synaptic plasticity, and apoptosis, were examined. Results: In S334ter-line-3 rats, TES induced anxiolytic and antidepressant-like behaviors in the cylinder, open field, home cage emergence, and forced swim tests. In the CUS rat model, TES induced hedonic-like behavior and decreased behavioral despair, which were accompanied by reduced plasma corticosterone levels and upregulated expression of neurogenesis-related genes. Treatment with the neurogenesis blocker temozolomide only inhibited the hedonic-like effect of TES, suggesting the antidepressant-like effects of TES were mediated through both neurogenesis-dependent and -independent mechanisms. Furthermore, TES was found to normalize the protein expression of synaptic markers and apoptotic Bcl-2-associated X protein in the hippocampus and amygdala in the CUS rat model. The improvements in neuroplasticity may involve protein kinase B (AKT) and protein kinase A (PKA) signaling pathways in the hippocampus and amygdala, respectively, as demonstrated by the altered pAKT/AKT and pPKA/PKA ratios. Conclusion: The overall findings suggest a possible neuroplasticity mechanism of the antidepressant-like effects of TES.

Alzheimer’s disease (AD) is a neurodegenerative disorder, and no effective treatments are available to treat this disorder. Therefore, researchers have been investigating Hericium erinaceus, or the monkey head mushroom, an edible medicinal mushroom, as a possible treatment for AD. In this narrative review, we evaluated six preclinical and three clinical studies of the therapeutic effects of Hericium erinaceus on AD. Preclinical trials have successfully demonstrated that extracts and bioactive compounds of Hericium erinaceus have potential beneficial effects in ameliorating cognitive functioning and behavioral deficits in animal models of AD. A limited number of clinical studies have been conducted and several clinical trials are ongoing, which have thus far shown analogous outcomes to the preclinical studies. Nonetheless, future research on Hericium erinaceus needs to focus on elucidating the specific neuroprotective mechanisms and the target sites in AD. Additionally, standardized treatment parameters and universal regulatory systems need to be established to further ensure treatment safety and efficacy. In conclusion, Hericium erinaceus has therapeutic potential and may facilitate memory enhancement in patients with AD.

Autosomal recessive cerebellar ataxias (ARCAs) are a heterogeneous group of rare neurodegenerative inherited disorders. The resulting motor incoordination and progressive functional disabilities lead to reduced lifespan. There is currently no cure for ARCAs, likely attributed to the lack of understanding of the multifaceted roles of antioxidant defense and the underlying mechanisms. This systematic review aims to evaluate the extant literature on the current developments of therapeutic strategies that target oxidative stress for the management of ARCAs. We searched PubMed, Web of Science, and Science Direct Scopus for relevant peer-reviewed articles published from 1 January 2016 onwards. A total of 28 preclinical studies fulfilled the eligibility criteria for inclusion in this systematic review. We first evaluated the altered cellular processes, abnormal signaling cascades, and disrupted protein quality control underlying the pathogenesis of ARCA. We then examined the current potential therapeutic strategies for ARCAs, including aromatic, organic and pharmacological compounds, gene therapy, natural products, and nanotechnology, as well as their associated antioxidant pathways and modes of action. We then discussed their potential as antioxidant therapeutics for ARCAs, with the long-term view toward their possible translation to clinical practice. In conclusion, our current understanding is that these antioxidant therapies show promise in improving or halting the progression of ARCAs. Tailoring the therapies to specific disease stages could greatly facilitate the management of ARCAs.

BackgroundIn recent years, telehealth has become a common channel for health care professionals to use to promote health and provide distance care. COVID-19 has further fostered the widespread use of this new technology, which can improve access to care while protecting the community from exposure to infection by direct personal contact, and reduce the time and cost of traveling for both health care users and providers. This is especially true for community-dwelling older adults who have multiple chronic diseases and require frequent hospital visits. Nurses are globally recognized as health care professionals who provide effective community-based care to older adults, facilitating their desire to age in place. However, to date, it is unclear whether the use of telehealth can facilitate their work of promoting self-care to community-dwelling older adults. ObjectiveThis review aims to summarize findings from randomized controlled trials on the effect of nurse-led telehealth self-care promotion programs compared with the usual on-site or face-to-face services on the quality of life (QoL), self-efficacy, depression, and hospital admissions among community-dwelling older adults. MethodsA search of 6 major databases was undertaken of relevant studies published from May 2011 to April 2021. Standardized mean differences (SMDs) and their 95% CIs were calculated from postintervention outcomes for continuous data, while the odds ratio was obtained for dichotomous data using the Mantel–Haenszel test. ResultsFrom 1173 possible publications, 13 trials involving a total of 4097 participants were included in this meta-analysis. Compared with the control groups, the intervention groups of community-dwelling older adults significantly improved in overall QoL (SMD 0.12; 95% CI 0.03 to 0.20; P=.006; I2=21%), self-efficacy (SMD 0.19; 95% CI 0.08 to 0.30; P

Transcorneal electrical stimulation (TES) has emerged as a non-invasive neuromodulation approach that exerts neuroprotection via diverse mechanisms, including neurotrophic, neuroplastic, anti-inflammatory, anti-apoptotic, anti-glutamatergic, and vasodilation mechanisms. Although current studies of TES have mainly focused on its applications in ophthalmology, several lines of evidence point towards its putative use in treating depression. Apart from stimulating visual-related structures and promoting visual restoration, TES has also been shown to activate brain regions that are involved in mood alterations and can induce antidepressant-like behaviour in animals. The beneficial effects of TES in depression were further supported by its shared mechanisms with FDA-approved antidepressant treatments, including its neuroprotective properties against apoptosis and inflammation, and its ability to enhance the neurotrophic expression. This article critically reviews the current findings on the neuroprotective effects of TES and provides evidence to support our hypothesis that TES possesses antidepressant effects.