Unveiling the hidden pathways: Exploring astrocytes as a key target for depression therapy.

Depressive disorders are widely debilitating psychiatric disease. Despite the considerable progress in the field of depression therapy, extensive research spanning many decades has failed to uncover pathogenic pathways that might aid in the creation of long-acting and rapid-acting antidepressants. Consequently, it is imperative to reconsider existing approaches and explore other targets to improve this area of study. In contemporary times, several scholarly investigations have unveiled that persons who have received a diagnosis of depression, as well as animal models employed to study depression, demonstrate a decrease in both the quantity as well as density of astrocytes, accompanied by alterations in gene expression and morphological attributes. Astrocytes rely on a diverse array of channels and receptors to facilitate their neurotransmitter transmission inside tripartite synapses. This study aimed to investigate the potential processes behind the development of depression, specifically focusing on astrocyte-associated neuroinflammation and the involvement of several molecular components such as connexin 43, potassium channel Kir4.1, aquaporin 4, glutamatergic aspartic acid transporter protein, SLC1A2 or GLT-1, glucocorticoid receptors, 5-hydroxytryptamine receptor 2B, and autophagy, that localized on the surface of astrocytes. The study also explores novel approaches in the treatment of depression, with a focus on astrocytes, offering innovative perspectives on potential antidepressant medications.

Global trends in tumor microenvironment-related research on tumor vaccine: a review and bibliometric analysis.

Background: Tumor vaccines have become crucial in cancer immunotherapy, but, only a limited number of phase III clinical trials have demonstrated clinical efficacy. The crux of this issue is the inability of tumor vaccines to effectively harmonize the tumor microenvironment with its intricate interplay. One factor that can hinder the effectiveness of vaccines is the natural immunosuppressive element present in the tumor microenvironment. This element can lead to low rates of T-cell response specific to antigens and the development of acquired resistance. Conversely, anticancer vaccines alter the tumor microenvironment in conflicting manners, inducing both immune activation and immunological evasion. Hence, comprehending the correlation between tumor vaccines and the tumor microenvironment would establish a foundation for forthcoming tumor treatment. Objective: Our review explores the realm of research pertaining to tumor vaccinations and the tumor microenvironment. Our objective is to investigate the correlation between tumor vaccines and the tumor microenvironment within this domain. We then focus our review on the dominant international paradigms in this research field and visually illustrates the historical progression and emergent patterns observed in the past. Methods: From January 1, 1999 to February 7, 2023, 1420 articles on the interplay between tumor vaccines and the tumor microenvironment were published, according to The Clarivate Web of Science (WOS) database used in our review. A bibliometric review was designed for this collection and consisted of an evaluation. The evaluation encompassed various discernible attributes, including the year of publication, the journals in which the articles were published, the authors involved, the affiliated institutions, the geographical locations of the institutions, the references cited, and the keywords employed. Results: Between the years 1999 and 2022, publications saw a significant increase, from 3 to 265 annually. With 72 papers published, Frontiers in Immunology had the most manuscripts published. The Cancer Research publication garnered the highest number of citations, amounting to 2874 citations. The United States exerts significant dominance in the subject, with the National Cancer Institute being recognized as a prominent institution in terms of both productivity and influence. Furthermore, Elizabeth M. Jaffee was recognized as the field's most prolific and influential author with 24 publications and 1,756 citations. The co-occurrence cluster analysis was conducted on the top 197 keywords, resulting in the identification of five distinct clusters. The most recent high-frequency keywords, namely immune therapy, dendritic cell, tumor microenvironment, cancer, and vaccine, signify the emerging frontiers in the interaction between tumor vaccines and the tumor microenvironment. Conclusion: Our review uncovers insights into contemporary trends, global patterns of collaboration, fundamental knowledge, research areas of high interest, and emerging frontiers in the field of TME-targeted vaccines.

Asperulosidic Acid Restrains Hepatocellular Carcinoma Development and Enhances Chemosensitivity Through Inactivating the MEKK1/NF-κB Pathway.

Asperulosidic acid (ASPA) is a plant-extracted iridoid terpenoid with tumor-suppressive and anti-inflammatory properties. At present, the antitumor function of ASPA and its related mechanisms in hepatocellular carcinoma (HCC) cells were explored. Human normal hepatocytes HL-7702 and HCC cells (Huh7 and HCCLM3) were treated with varying concentrations (0 to 200 µg/mL) of ASPA. Cell viability, proliferation, apoptosis, migration, and invasion were checked. The expression of proteins was detected by Western blot. Furthermore, the effect of ASPA (100 µg/mL) on the sensitivity of HCC cells to chemotherapeutic agents, including doxorubicin and cisplatin, was evaluated. A subcutaneous xenografted tumor model was set up in nude mice, and the antitumor effects of ASPA were evaluated. ASPA hindered HCC cells' proliferation, migration, and invasion, and amplified their apoptosis and sensitivity to chemotherapeutic agents. Additionally, ASPA inactivated the MEKK1/NF-κB pathway. Overexpression of MEKK1 increased HCC proliferation, migration, and invasion and facilitated chemoresistance. ASPA treatment alleviated the carcinogenic effect mediated by MEKK1 overexpression. MEKK1 knockdown slowed down HCC progression. However, ASPA could not exert additional antitumor effects in MEKK1 knockdown cells. In vivo results displayed that ASPA substantially curbed tumor growth and inactivated the MEKK1/NF-κB pathway in mice. All over, ASPA exerts antitumor effects in HCC by suppressing the MEKK1/NF-κB pathway.

Neurological and metabolic related pathophysiologies and treatment of comorbid diabetes with depression.

BACKGROUND: The comorbidity between diabetes mellitus and depression was revealed, and diabetes mellitus increased the prevalence of depressive disorder, which ranked 13th in the leading causes of disability-adjusted life-years. Insulin resistance, which is common in diabetes mellitus, has increased the risk of depressive symptoms in both humans and animals. However, the mechanisms behind the comorbidity are multi-factorial and complicated. There is still no causal chain to explain the comorbidity exactly. Moreover, Selective serotonin reuptake inhibitors, insulin and metformin, which are recommended for treating diabetes mellitus-induced depression, were found to be a risk factor in some complications of diabetes. AIMS: Given these problems, many researchers made remarkable efforts to analyze diabetes complicating depression from different aspects, including insulin resistance, stress and Hypothalamic-Pituitary-Adrenal axis, neurological system, oxidative stress, and inflammation. Drug therapy, such as Hydrogen Sulfide, Cannabidiol, Ascorbic Acid and Hesperidin, are conducive to alleviating diabetes mellitus and depression. Here, we reviewed the exact pathophysiology underlying the comorbidity between depressive disorder and diabetes mellitus and drug therapy. METHODS: The review refers to the available literature in PubMed and Web of Science, searching critical terms related to diabetes mellitus, depression and drug therapy. RESULTS: In this review, we found that brain structure and function, neurogenesis, brain-derived neurotrophic factor and glucose and lipid metabolism were involved in the pathophysiology of the comorbidity. Obesity might lead to diabetes mellitus and depression through reduced adiponectin and increased leptin and resistin. In addition, drug therapy displayed in this review could expand the region of potential therapy. CONCLUSIONS: The review summarizes the mechanisms underlying the comorbidity. It also overviews drug therapy with anti-diabetic and anti-depressant effects.

Global trends in COVID-19 Alzheimer's related research: a bibliometric analysis.

Background: The COVID-19 pandemic has significantly impacted public health, putting people with Alzheimer's disease at significant risk. This study used bibliometric analysis method to conduct in-depth research on the relationship between COVID-19 and Alzheimer's disease, as well as to predict its development trends. Methods: The Web of Science Core Collection was searched for relevant literature on Alzheimer's and Coronavirus-19 during 2019-2023. We used a search query string in our advanced search. Using Microsoft Excel 2021 and VOSviewer software, a statistical analysis of primary high-yield authors, research institutions, countries, and journals was performed. Knowledge networks, collaboration maps, hotspots, and regional trends were analyzed using VOSviewer and CiteSpace. Results: During 2020-2023, 866 academic studies were published in international journals. United States, Italy, and the United Kingdom rank top three in the survey; in terms of productivity, the top three schools were Harvard Medical School, the University of Padua, and the University of Oxford; Bonanni, Laura, from Gabriele d'Annunzio University (Italy), Tedeschi, Gioacchino from the University of Campania Luigi Vanvitelli (Italy), Vanacore, Nicola from Natl Ctr Dis Prevent and Health Promot (Italy), Reddy, P. Hemachandra from Texas Tech University (USA), and El Haj, Mohamad from University of Nantes (France) were the authors who published the most articles; The Journal of Alzheimer's Disease is the journals with the most published articles; "COVID-19," "Alzheimer's disease," "neurodegenerative diseases," "cognitive impairment," "neuroinflammation," "quality of life," and "neurological complications" have been the focus of attention in the last 3 years. Conclusion: The disease caused by the COVID-19 virus infection related to Alzheimer's disease has attracted significant attention worldwide. The major hot topics in 2020 were: "Alzheimer' disease," COVID-19," risk factors," care," and "Parkinson's disease." During the 2 years 2021 and 2022, researchers were also interested in "neurodegenerative diseases," "cognitive impairment," and "quality of life," which require further investigation.

The benefits of hesperidin in central nervous system disorders, based on the neuroprotective effect.

Disorders of central nervous system (CNS) disorders are considered serious health issues. The most common CNS diseases include neurodegenerative diseases, mental disorders, demyelinating disease, ischemia-reperfusion injury, and neuroinflammation. As a natural phenolic compound, hesperidin is a flavanone glycoside with various biological effects. Increasing evidence show that the growth of CNS diseases is hindered by hesperidin. Here, we have reviewed the related literature on neuropharmacological mechanisms for the preventive and therapeutic effects of hesperidin on CNS diseases. Several cellular and animal models have been developed to evaluate the underlying neuropharmacological mechanisms of hesperidin. Additionally, clinical evidence has confirmed its neuroprotective function. Hesperidin exerts its neuroprotective properties by decreasing neuro-inflammatory and apoptotic pathways. Hesperidin function has been studied in preclinical models for CNS diseases, but little is known about its definite effect in humans. Hesperidin can effectively alleviate depression and improve cognition and memory. It is urgent to explore and discover clinical trials for further confirmation of the neuroprotective efficacy of hesperidin and to evaluate its safety profile.