Potential Mechanisms Research Articles

Dapagliflozin Alleviates Myocardial Ischaemia Reperfusion Injury by Activating Mitophagy via the AMPK-PINK1/Parkin Signalling Pathway.

Myocardial ischaemia reperfusion injury (MIRI) determines infarct size and long-term outcomes after acute myocardial infarction (AMI). Dapagliflozin, a sodium-glucose cotransporter 2 inhibitor, alleviates MIRI in animal models. We investigated the potential mechanisms underlying the cardioprotective effect of dapagliflozin against MIRI, focusing on mitochondrial injury and mitophagy. MIRI mouse and H9C2 cell models were established. 2,3,5-Triphenyltetrazolium chloride (TTC) staining showed a significant alleviation of MIRI after pre-treatment of dapagliflozin compared to the model group (14.91 ± 1.76 vs. 40.47 ± 3.69%). Data from the pre-treatment dapagliflozin group showed a significant decrease in left ventricular ejection fraction (LVEF) (44.8 ± 2.7 vs. 28.5 ± 5.3%, P<0.01), left ventricular end-diastolic volume (LVEDV) (70.6 ± 9.5 vs. 93.5 ± 13.8 ul, P<0.05), and left ventricular end-systolic volume (LVESV) (39.0 ± 8.3 vs. 67.9 ± 13.7 ul, P<0.05) compared to the model group. Dapagliflozin also reduced the levels of reactive oxygen species (ROS) and fragmented mitochondrial DNA, reversed the decrease in mitochondrial membrane potential, and suppressed apoptosis. Further study showed that dapagliflozin could protect against mitochondrial injury by rapidly clearing damaged mitochondria via mitophagy in a phosphatase and tensin homologue (PTEN)-induced putative kinase 1 (PINK1)/parkindependent manner. Dapagliflozin regulated mitophagy in cardiomyocytes by suppressing the adenosine 5'monophosphate-activated protein kinase (AMPK)-PINK1/parkin signalling pathway, resulting in attenuated MIRI. Dapagliflozin alleviated MIRI by activating mitophagy via the AMPK-PINK1/parkin signalling pathway.

Who will Spend more Pollution Abatement Costs: does Size Matter?

This paper looks at the relationship between enterprise size and pollution abatement costs using firm-level datasets in China, where size-dependent distortions may exist in the distribution of enterprises of different sizes. We find that the pollution abatement costs decrease with enterprise size. Compared to the smallest size, the magnitudes of marginal decreases in pollution abatement costs per 1000 CNY of industrial output in the largest size are 3.29 CNY, 0.54 CNY and 2.60 CNY for gas, SO2 and dust, respectively. Moreover, we further explore the potential mechanisms for the decrease of pollution abatement costs from three perspectives: environmental protection-related investment, regulation intensity, and technological capability. Our findings suggest that the decrease in the intensity of environmental protection-related investment for large enterprises may be directly reduce the intensity of pollution abatement costs. Although large enterprises have low intensity of pollution abatement costs, this does not mean that they are subject to weaker environmental regulation. More importantly, we find that large enterprises may have more adoption of abatement technologies. For SO2 and dust, the pollutant removal efficiency of the largest enterprises is 4.92% and 1.82% higher than that of the smallest enterprises, respectively. Our results are robust to different specifications. These findings help us enact appropriate policies for enterprises based on their size, thereby improving the efficacy of pollution abatement and achieving the optimal level of pollution abatement for the entire society.

Persist or Perish: Can Bats Threatened with Extinction Persist and Recover from White-nose Syndrome?

Emerging mycoses are an increasing concern in wildlife and human health. Given the historical rarity of fungal pathogens in warm-bodied vertebrates, there is a need to better understand how to manage mycoses and facilitate recovery in affected host populations. We explore challenges to host survival and mechanisms of host recovery in three bat species (Myotis lucifugus, Perimyotis subflavus, and M. septentrionalis) threatened with extinction by the mycosis, white-nose syndrome (WNS) as it continues to spread across North America. We present evidence from the literature that bats surviving WNS are exhibiting mechanisms of avoidance (by selecting microclimates within roosts) and tolerance (by increasing winter fat reserves), which may help avoid costs of immunopathology incurred by a maladaptive host resistance response. We discuss management actions for facilitating species recovery that take into consideration disease pressures (e.g., environmental reservoirs) and mechanisms underlying persistence, and suggest strategies that alleviate costs of immunopathology and target mechanisms of avoidance (protect or create refugia) and tolerance (increase body condition). We also propose strategies that target population and species-level recovery, including increasing reproductive success and reducing other stressors (e.g., wind turbine mortality). The rarity of fungal pathogens paired with the increasing frequency of emerging mycoses in warm-bodied vertebrate systems, including humans, requires a need to challenge common conventions about how diseases operate, how hosts respond, and how these systems could be managed to increase probability of recovery in host populations.

Role of delay discounting in resisting in-class media multitasking under contextual control: a cluster analysis

ABSTRACT The present study examined a potential mechanism underlying college students’ resisting in-class media multitasking under contextual control from a behavioural economic perspective. Using a hierarchical cluster analysis, we first identified subgroups of students who differed in frequencies of media multitasking across two contexts (preferred and non-preferred classes). We then compared a subgroup of students who could resist media multitasking in one context but not in another context with other subgroups of students in terms of rates of delay discounting and levels of impulse control. In the delay-discounting task, participants made a series of choices between smaller amounts of hypothetical monetary rewards available immediately and a larger amount of hypothetical monetary rewards available after a delay. Impulse control was measured by a self-reported scale. The primary finding was that the subgroup of students who could resist media multitasking in preferred but not non-preferred classes showed significantly lower rates of delay discounting than the subgroup of students who frequently engaged in media multitasking in both preferred and non-preferred classes. Implications for developing effective intervention strategies from a behavioural economic perspective are discussed.

Electric-thermal-mechanics modeling for in-process phenomena during micro resistance spot welding spark plug of Pt and Inconel600

The spark plug is one of the important components in the gasoline engine's combustion chamber. To reduce vehicle emissions, the platinum spark plug is selected due to its good performance. Due to the high productivity of resistance spot welding (RSW), a micro-scale RSW process is employed to assemble the platinum tip to Inconel600 part in the production of spark plugs. In order to understand the electric-thermal-mechanics phenomena during micro resistance spot welding spark plug for controlling the welding quality and saving electric energy, a three-dimensional simulation model and the in-house finite element program JWRIAN-RSW3D were developed. The potential history and upper electrode displacement results were verified with experiments. Numerical case studies were made to investigate the influence magnitude of welding current on the electric-thermal-mechanics phenomena. The developed model reveals inside phenomena to clearly understand the welding mechanism for potential, current density, temperature, electrode displacement and their distribution/history as well as the molten zone. The comprehensive phenomena of maximum temperature distribution on both base metals and Inconel600 were clarified using a top perspective, revealing differences in distribution on the contact surface between horizontal and vertical sections. To achieve a complete welding joint, the molten zone on the contact area is required carefully in order to facilitate the bonding of both base metals. Based on simulation results for three welding conditions, the alternating current at the magnitude of 1.2 kA with the welding time of 0.1 s is recommended to obtain the welded joint with minimized energy consumption in production.

WITHDRAWN: Transdifferentiation of Human Neonatal Foreskin Fibroblasts into Keratinocyte-like Cells via Regulating the AKT/P53/WNT/LEF1 Axis

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Association of Antipsychotic Drugs with Venous Thromboembolism: Data Mining of Food and Drug Administration Adverse Event Reporting System and Mendelian Randomization Analysis.

Past observational studies have reported on the association between antipsychotic drugs and venous thromboembolism (VTE); however, the conclusions remain controversial, and its mechanisms are yet to be fully understood. Thus, in this study, we aim to determine the associations of antipsychotic drugs with VTE, including deep vein thrombosis (DVT) and pulmonary embolism (PE), and their potential mechanisms. We first mined the adverse event signals of VTE, DVT, and PE caused by antipsychotic drugs in Food and Drug Administration Adverse Event Reporting System (FAERS). Next, we used two-sample Mendelian randomization (MR) method to investigate the association of antipsychotic drug target gene expression with VTE, DVT, and PE, using single-nucleotide polymorphisms as genetic instruments. We not only used the expression of all antipsychotic drug target genes as exposure to perform MR analyses but also analyzed the effect of single target gene expression on the outcomes. In the FAERS, 1694 cases of VTE events were reported by 16 drugs. However, using the MR approach, no significant association was determined between the expression of all antipsychotic target genes and VTE, DVT, or PE, either in blood or brain tissue. Although the analysis of single gene expression data showed that the expression of nine genes was associated with VTE events, these targets lacked significant pharmacological action. Adverse event mining results have supported the claim that antipsychotic drugs can increase the risk of VTE. However, we failed to find any genetic evidence for this causal association and potential mechanisms. Thus, vigilance is still needed for antipsychotic drug-related VTE despite the limited supporting evidence.

Childhood trauma, stressful life events, and depression: Exploring the mediating effect of cognitive flexibility.

Childhood trauma and stressful life events have been identified as risk factors for the development of depression. However, little is known about the potential cognitive mechanisms underlying these associations. This study aims to investigate the associations among childhood trauma, stressful life events, and depression and to test a mediating model to examine the roles of cognitive flexibility in these associations. First-year university students (n = 2627; Mage = 18.29, SDage = .86) were recruited from a medical university in Guangzhou, China. A total of 1,600 (60.9%) females and 1,027 (39.1%) males participated in the survey. Participants were administered self-report measures assessing childhood trauma, stressful life events, cognitive flexibility, and depression. Childhood trauma and stressful life events were both negative predictors of cognitive flexibility (β = -.32, β = -.19, respectively; ps < .01), which in turn was a negative predictor of depression (β = -.50, p < .01). Cognitive flexibility partially mediated the relationship between childhood trauma and depression (with the indirect effect = .161, 95% confidence interval, CI [.139, .185]) as well as the relationship between stressful life events and depression (with the indirect effect = .097, 95% CI [.078, .118]). This study reveals that childhood trauma and stressful life events not only have a direct effect on depression but also increase individuals' risk of depression by decreasing their cognitive flexibility. These findings shed light on the possible potential mechanism underlying the suicide process and highlight the important role of cognitive flexibility in suicide prevention and intervention. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Natural Polyphenols in Cancer Management: Promising Role, Mechanisms, and Chemistry.

Although cancers emerge rapidly and cancer cells divide aggressively, which affects our vital organ systems. Recently, cancer treatments are targeted immune systems mediating intrinsic cellular mechanisms. Natural efficacious polyphenols have been exhibited to help prevent most cancers and reverse the progression of cancers. Many resources have been used to know the promising role of polyphenols in preventing and treating cancers. The electronic databases include Science Direct, Google, Google Scholar, PubMed, and Scopus. The search was limited to the English language only. Polyphenols have been reported as anti-metastatic agents that explore the promising role of these compounds in cancer prevention. Such agents act through many signaling pathways, including PI3K/Akt and TNF-induced signaling pathways. The chemical modifications of polyphenols and the structure-activity relationships (SARs) between polyphenols and anticancer activities have also been discussed. Many research papers were reported to explain the anti-cancer potential of Polyphenols, The SARs between polyphenols and anti-cancer activities, which correlate structures of polyphenols with significant chemotherapeutic action. The mechanism of anti-cancer potential is to be added for searching for new anti-cancer natural products.

Fluoroquinolone and enoxacin molecules are potential urease inhibitors for treating ureolytic bacterial infections

Urease, a nickel-dependent metalloenzyme, has emerged as a significant therapeutic target due to its role in promoting the pathogenesis of various human health conditions. These include the development of pyelonephritis, urolithiasis, peptic ulcers, hepatic encephalopathy, and gastric ulcers. The currently available treatment involved the usage of strong antibiotics along with proton pump inhibitors to cope with the infection of urease producing bacteria. These conventional treatments are becoming less effective as bacteria are gaining multiple drug resistance. Therefore, there is a crucial need to identify alternative compounds with potential anti-urease activity and minimal side effects. Fluoroquinolones and Enoxacin derivatives offer antimicrobial, anti-inflammatory, antioxidant, anti-diabetic, and anti-urease activities. To improve the chemical diversity of urease inhibitors, different series of fluoroquinolones and Enoxacin derivatives were evaluated against urease and their antioxidant activity was also evaluated. To achieve this objective, in-silico studies were conducted utilizing molecular docking and adsorption, distribution, metabolism, excretion, and toxicology (ADMET) models. These analyses were employed to explore potential binding mechanisms and assess the drug-likeness of the compounds against urease enzymes. The inhibitory effect of docked heterocyclic compounds was also verified in-vitro against urease enzyme. Fluoroquinolones derivatives were found to be active inhibitors at high dose levels but showed minimum inhibition at low concentration. The compound EN from the Enoxacin series exhibited the highest potency as a urease inhibitor, with an IC50 of 45.86 μM, out-performing the standard drug thiourea, which had an IC50 of 52.20 μM. Additionally, compounds NOX-3 and FB-17 from the fluoroquinolone and Enoxacin series demonstrated significant DPPH free radical scavenging activity, with IC50 values of 98.17 μM and 97.98 μM, respectively. These results were comparable to the positive control ascorbic acid, which had an IC50 of 48.15 μM. This study demonstrates that Enoxacin derivatives can be further analyzed as potent urease inhibitors, while both Enoxacin and fluoroquinolone derivatives can be developed into more effective drugs to overcome oxidative stress.

Cultural mechanisms linking mothers' familism values to externalizing behaviors among Midwest U.S. Latinx adolescents.

This study was designed to examine associations among parents' familism values, adolescents' cultural resources, and externalizing behavior among Latinx youth in the Midwestern United States. Participants were 267 Latinx adolescents (M age = 15.58 years; SD = 1.28 years; 45% girls; 82.8% Mexican American) and their mothers/mother figures who completed individually administered interviews comprised of standardized measures. Structural equation modeling was used to test several alternative mediational models in which youth ethnic identity and familism values served as potential cultural mechanisms linking parents' familism values to lower levels of youth externalizing behavior. Results showed that mothers' familism values were positively associated with youth ethnic identity which was positively associated with youth familism values; in turn, youth familism values were inversely associated with externalizing behavior. The findings did not differ by youth gender or nativity (U.S.-born vs. foreign-born youth). These findings provide support for cultural resilience perspectives by highlighting the protective role of ethnic identity and familism values among U.S. Latinx adolescents. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Crosstalk of lysyl oxidase-like 1 and lysyl oxidase prolongs their half-lives and regulates liver fibrosis through Notch signal.

Lysyl oxidase (LOX) family members (LOX and LOXL1 to 4) are crucial copper-dependent enzymes responsible for cross-linking collagen and elastin. Previous studies have revealed that LOX and LOXL1 are the most dramatically dysregulated LOX isoforms during liver fibrosis. However, the crosstalk between them and the underlying mechanisms involved in the profibrotic behaviors of HSCs, as well as the progression of liver fibrosis, remain unclear. pCol9GFP-HS4,5Tg mice, Loxl1fl/flGfapCre mice, human HSC line, and primary HSCs were enrolled to study the dysregulation pattern, profibrotic roles, and the potential mechanisms of LOX and LOXL1 interaction involved in the myofibroblast-like transition of HSCs and liver fibrogenesis. LOX and LOXL1 were synergistically upregulated during liver fibrogenesis, irrespective of etiology, together orchestrating the profibrotic behaviors of HSCs. LOX and LOXL1 coregulated in HSCs, whereas LOXL1 dominated in the coregulation loop. Interestingly, the interaction between LOXL1 and LOX prolonged their half-lives, specifically enhancing the Notch signal-mediated myofibroblast-like transition of HSCs. Selective disruption of Loxl1 in Gfap+ HSCs deactivated the Notch signal, inhibited HSC activation, and relieved carbon tetrachloride-induced liver fibrosis. Our current study confirmed the synergistic roles and the underlying mechanisms of LOXL1 and LOX crosstalk in the profibrotic behaviors of HSCs and liver fibrosis progression, providing experimental evidence for further clear mechanism-based anti-LOXL1 strategy development in the therapy of liver fibrosis.

Cutaneous targets for topical pain medications in patients with neuropathic pain: individual differential expression of biomarkers supports the need for personalized medicine.

Numerous potential cutaneous targets exist for treating chronic pain with topically applied active pharmaceutical ingredients. This preliminary human skin tissue investigation was undertaken to characterize several key biomarkers in keratinocytes and provide proof-of-principle data to support clinical development of topical compounded formulations for peripheral neuropathic pain syndromes, such as postherpetic neuralgia (PHN). The study intended to identify objective biomarkers in PHN skin on a patient-by-patient personalized medicine platform. The totality of biopsy biomarker data can provide a tissue basis for directing individualized compounded topical preparations to optimize treatment efficacy. Referencing 5 of the most common actives used in topical pain relief formulations (ketamine, gabapentin, clonidine, baclofen, and lidocaine), and 3 well-established cutaneous mediators (ie, neuropeptides, cannabinoids, and vanilloids), comprehensive immunolabeling was used to quantify receptor biomarkers in skin biopsy samples taken from ipsilateral (pain) and contralateral (nonpain) dermatomes of patients with PHN. Epidermal keratinocyte labeling patterns were significantly different among the cohort for each biomarker, consistent with potential mechanisms of action among keratinocytes. Importantly, the total biomarker panel indicates that the enriched PHN cohort contains distinct subgroups. The heterogeneity of the cohort differences may explain studies that have not shown statistical group benefit from topically administered compounded therapies. Rather, the essential need for individual tissue biomarker evaluations is evident, particularly as a means to direct a more accurately targeted topical personalized medicine approach and generate positive clinical results.

Precision Education and Equity: A Participatory Framework to Advance Equitable Assessment.

Precision education (PE) may hold promise for the future of the field. Leveraging data and learning analytics to foster continuous improvement of individuals, programs, and organizations seems like a potential mechanism to advance both medical education and health care delivery systems toward a more equitable future. However, PE initiatives may also have unintended consequences and perpetuate inequities instead of ameliorating them. Although there have been some principles, ideas, and suggestions on how PE implementation may promote equity-particularly for the field of assessment-there is a lack of practical and evidence-informed guidance to support a more equitable and participatory approach to PE implementation. This paper provides actionable recommendations on how PE may advance equitable assessment. First, PE implementation must include democratizing access and ownership while enhancing literacy and transparency. Open and transparent access to both data and PE technology has the potential to enhance PE by fostering greater participation, rigor, and potential innovation. Transparency may also safeguard the use of assessment data for equitable purposes. Second, PE implementation must be cocreated with diverse learners. PE has the potential to empower learners if they are given an opportunity to participate in the development, application, and implementation of PE. Overall, a participatory approach to PE implementation has the potential to improve equitable assessment.

Skin-derived precursor conditioned medium alleviated photoaging via early activation of TGF-β/Smad signaling pathway by thrombospondin1: In vitro and in vivo studies

Photoaging is one major exogenous factor of skin aging. Efficacy and safety of current anti-photoaging therapies remained to be improved. Our previous studies indicated that skin-derived precursors (SKPs) alleviated photodamage by early activation of TGF-β/Smad signaling pathway via thrombospondin1 (TSP1). However, the research concerning SKP conditioned medium (SKP-CM) has never been reported. In the current study, we aimed to explore the anti-photoaging effects of SKP-CM both in vitro and in vivo, and to elucidate the possible mechanisms. Mouse SKP-CM (mSKP-CM) collection was optimized by a comparative method. The concentration of protein and growth factors in mSKP-CM was detected using BCA protein assay kit and growth factor protein chip. The anti-photoaging effects of mSKP-CM and its regulation of key factors in the TGF-β/Smad signaling pathway were explored using UVA + UVB photoaged mouse fibroblasts (mFBs) and nude mice dorsal skin. The research revealed that mSKP-CM contained significantly higher-concentration of protein and growth factors than mouse mesenchymal stem cell conditioned medium (mDMSC-CM). mSKP-CM alleviated mFBs photoaging by restoring cell viability and relieving senescence and death. ELISA, qRT-PCR, and western blot results implied the potential mechanisms were associated with the early activation of TGF-β/Smad signaling pathway by TSP1. In vivo experiments demonstrated that compared with the topical intradermal mDMSC-CM injection and retinoic acid cream application, the photodamaged mice dorsal skin intradermally injected with mSKP-CM showed significantly better improvement. Consistent with the in vitro results, both western blot and immunohistochemistry results confirmed that protein expression of TSP1, smad2/3, p-smad2/3, TGF-β1, and collagen I increased, and matrix metalloproteinases decreased. In summary, both in vitro and in vivo experiments demonstrated that mSKP-CM alleviated photoaging through an early activation of TGF-β/Smad signaling pathway via TSP1. SKP-CM may serve as a novel and promising cell-free therapeutical approach for anti-photoaging treatment and regenerative medicine.

Network Pharmacology and Intestinal Microbiota Analysis Revealing the Mechanism of Punicalagin Improving Bacterial Enteritis.

The Chinese medicine punicalagin (Pun), the most important active ingredient in pomegranate peel, has significant bacteriostatic and anti-inflammatory properties. The potential mechanisms of Pun for bacterial enteritis, however, are unknown. The goal of our research is to investigate the mechanism of Pun in the treatment of bacterial enteritis using computer-aided drug technology, as well as to investigate the intervention effect of Pun on mice with bacterial enteritis using intestinal flora sequencing. The targets of Pun and Bacterial enteritis were obtained by using the specific database, and cross-targets were screened among these targets, followed by PPI and enrichment analysis of the targets. Furthermore, the degree of binding between Pun and key targets was predicted through molecular docking. After successfully establishing the bacterial enteritis model in vivo, mice were randomly assigned to groups. They were treated for 7 days, the symptoms were observed daily, and the daily DAI and body weight change rate were calculated. Following administration, the intestinal tissue was removed, and the contents were separated. The tight junction protein expression was detected in the small intestine by the immunohistochemical method; ELISA and Western Blot (WB) were performed to detect the expressions of tumor necrosis factor-α (TNF-α) and interleukin- 6 (IL-6) in the serum and intestinal wall of mice. The 16S rRNA sequence was used to determine the composition and diversity of the intestinal flora of mice. In total, 130 intersection targets of Pun and disease were screened by network pharmacology. The enrichment analysis showed cross genes were closely related and enriched in the cancer regulation and the TNF signal pathway. The active components of Pun could specifically bind to the core targets TNF, IL-6, etc., determined from molecular docking results. In vivo experiment results showed that the symptoms in the PUN group mice were alleviated, and the expression levels of TNF-α and IL-6 were significantly reduced. A Pun can cause substantial changes in the intestinal flora of mice in terms of structure and function. Pun plays a multi-target role in alleviating bacterial enteritis by regulating intestinal flora.

Exploring the Molecular Mechanism of HongTeng Decoction against Inflammation based on Network Analysis and Experiments Validation.

HongTeng Decoction (HTD) is a traditional Chinese medicine that is widely used to treat bacterial infections and chronic inflammation. However, its pharmacological mechanism is not clear. Here, network pharmacology and experimental verification were applied to investigate the drug targets and potential mechanisms of HTD in inflammation treatment. The active ingredients of HTD were collected from the multi-source databases and clarified by Q Exactive Orbitrap analysis in the treatment of inflammation. Then, molecular docking technology was used to explore the binding ability of key active ingredients and targets in HTD. In vitro experiments, the inflammatory factors and MAPK signaling pathways are detected to verify the anti-inflammatory effect of HTD on the RAW264.7 cells. Finally, the anti-inflammatory effect of HTD was evaluated in LPS induced mice model. A total of 236 active compounds and 492 targets of HTD were obtained through database screening, and 954 potential targets of inflammation were identified. Finally, 164 possible targets of HTD acting on inflammation were obtained. The PPI analysis and KEGG enrichment analyses showed that the targets of HTD in inflammation were mostly related to the MAPK signaling pathway, the IL-17 signaling pathway, and the TNF signaling pathway. By integrating the results of the network analysis, the core targets of HTD in inflammation mainly include MAPK3, TNF, MMP9, IL6, EGFR, and NFKBIA. The molecular docking results indicated solid binding activity between MAPK3-naringenin and MAPK3-paeonol. It has been shown that HTD could inhibit the levels of inflammatory factors, IL6 and TNF-α, as well as the splenic index in the LPS-stimulated mice. Moreover, HTD could regulate protein expression levels of p-JNK1/2, and p-ERK1/2, which reflects the inhibitory effect of HTD on the MAPKS signaling pathway. Our study is expected to provide the pharmacological mechanisms by which HTD may be a promising anti-inflammatory drug for future clinical trials.

Terpenoids and Triterpenoid Saponins: Future Treatment for Depression

Background: Depression is a crippling mental disorder with high prevalence around the world. The available clinical antidepressants have been effective to a certain degree, and different side effects have limited their application. This leads to the necessity of finding new treatments. Herbal plants are a substantial source of new drug leads. Terpenoid compounds are secondary metabolites representing an enormous category of structures found commonly in plants either as aglycones or attached to sugar moieties. These phytochemicals have been extensively studied for their various biological effects, and several have been investigated for potential therapeutic effects in the treatment of depression. Aim: This review aims to highlight the current knowledge on some terpenoids and triterpenoid saponins as potential antidepressant agents and their mechanisms of action, which may provide a better understanding of the potential antidepressant-like effects of these compounds and lead to the development of auspicious molecules with high efficiency and low side effects for depressive disorders treatment. Methods: A total of 16 plants containing antidepressant agents are reviewed in this article. 9 terpenoids and 23 triterpenoid saponins compounds have been reported to becommonly found in plant extracts, indicating potential use for depression. To enhance the datum of this review, the mechanism of action for the candidate compounds has been predicted via functional enrichment analysis. Results: The behavioural and neurochemical effects, as well as the possible mechanisms of action, have been evaluated in rodents by different predictive models of depression, mainly the acute stress models of the forced swimming test (FST) and tail suspension test (TST). The involved mechanisms include enhancing monoamine neurotransmitters, ameliorating brain-derived neurotrophic factor (BDNF), and normalizing the hypothalamus-pituitary-adrenal (HPA) axis. Preclinical studies support the potential antidepressant activities of some terpenoid compounds. Furthermore, the functional enrichment analysis has confirmed the previous pre-clinical findings and predicted further mechanisms of action, including cellular calcium ion homeostasis, cellular response to dopamine, endocrine resistance, and regulating GABAergic, serotonergic, glutamatergic, and dopaminergic synapse, bedsides neurotransmitter reuptake. Conclusion: Terpenoids and triterpenoid saponins provide a large number of natural compounds. This review sheds light on terpenoids and triterpenoid saponins compounds with antidepressantlike activity and their potential mechanisms of action. However, more evaluations are required to confirm that these compounds are promising for discovering antidepressant drugs.

Dementia Disorders: A Narrative Review

This narrative review of research includes summaries of 40 papers on dementia disorders that were published during 2023. The publications of this period are primarily randomized controlled trials and systematic reviews/ meta-analyses of randomized controlled trials. A few of these are focused on the prevalence of dementia which approximated one per cent of the world’s population. Only a few studies focused on effects of dementia disorders including memory loss, discrimination, pain, depression and suicidality. Most of the studies addressed predictors of dementia disorders including neurotic personality, frequent tv/computer use and excessive exposure to metals. Loss of short-term memory and other negative experiences including negative life events, loneliness, stress and depression were also significant predictor variables in this recent literature. Physical conditions that were predictive of dementia included pain, hypertension, atrial fibrillation, multi-morbidities, inflammation, encephalitis and neuropathology. Potential underlying mechanisms included dysfunctional neurotransmitter systems (serotonergic, noradrenergic and dopaminergic) and gray matter loss in prefrontal, temporal and other regions associated with memory. Several research groups reported on effective interventions including a Mediterranean diet, plant-based diets, medicinal plants, psychedelics, second generation antidepressants, blood pressure medication, music therapy, aromatherapy and other alternative therapies. Methodological problems relate to the variability in the assessments of dementia disorders, the self-report measures and the cross-sectional data that are not definitive about directionality of predictors and effects of dementia disorders.

Children’s perceptions of animals in animal assisted interventions: a thematic synthesis

ABSTRACT There is growing interest in the animal assisted intervention (AAI) field to identify how participants benefit from their interaction with animals in these services. Although children frequently participate in these interventions, rarely have they been actively involved in research to explore how they experience the presence of an animal in AAI. This thematic synthesis pulls the few qualitative studies available that directly ask children who struggle with social and emotional difficulties abour their perception of their interactions with animals. Through the analysis of the findings of these studeis, a conceptual model is developed that identifies potential mechanisms that may influence the formation of a relationship between children and animals in AAI.