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Tetrahydropalmatine (THP), a tetrahydroproberine isoquinoline alkaloid, is widely present in some botanical drugs, such as Stephania epigaea H.S. Lo (Menispermaceae; Radix stephaniae epigaeae), Corydalis yanhusuo (Y.H.Chou & Chun C.Hsu) W.T. Wang ex Z.Y. Su and C.Y. Wu (Papaveraceae; Corydalis rhizoma), and Phellodendron chinense C.K.Schneid (Berberidaceae; Phellodendri chinensis cortex). THP has attracted considerable attention because of its diverse pharmacological activities. In this review, the chemical properties, plant sources, pharmacological activities, pharmacokinetic and toxicological characteristics of THP were systematically summarized for the first time. The results indicated that THP mainly existed in Papaveraceae and Menispermaceae families. Its pharmacological activities include anti-addiction, anti-inflammatory, analgesic, neuroprotective, and antitumor effects. Pharmacokinetic studies showed that THP was inadequately absorbed in the intestine and had rapid clearance and low bioavailability in vivo , as well as self-microemulsifying drug delivery systems, which could increase the absorption level and absorption rate of THP and improve its bioavailability. In addition, THP may have potential cardiac and neurological toxicity, but toxicity studies of THP are limited, especially its long-duration and acute toxicity tests. In summary, THP, as a natural alkaloid, has application prospects and potential development value, which is promising to be a novel drug for the treatment of pain, inflammation, and other related diseases. Further research on its potential target, molecular mechanism, toxicity, and oral utilization should need to be strengthened in the future.

As a central player in neuroinflammation, macrophages play multifaceted roles such as antigen presentation, phagocytosis, production of cytokines/chemokines, and growth/neurotrophic factors. Our previous work demonstrated that ocular infection with a recombinant herpes simplex virus type 1 (HSV-1) expressing interleukin-2 (HSV-IL-2) causes CNS pathology, independently of macrophages in different mouse strains. In contrast, wild type (WT) HSV-1 infection induces CNS demyelination in a macrophage-dependent manner. Therefore, in this study, we have two mouse models infected with either HSV-IL-2 or WT HSV-1 to examine the outcome of the absence of IL-17A, FoxP3, macrophages, or combined macrophage and FoxP3 depletion on CNS demyelination. Our data reveals several notable findings: deletion of FoxP3 alone in mice infected with either HSV-IL-2 or WT HSV-1 did not induce CNS demyelination. However, combined depletion of macrophages and FoxP3 in HSV-IL-2-infected mice triggered CNS demyelination, whereas the same combined depletion in WT HSV-1 infection prevented demyelination. Additionally, macrophage depletion alone in WT HSV-1-infected mice induced CNS demyelination, highlighting the non-redundant protective role of macrophages in this model. To further elucidate the role of macrophages in CNS demyelination, we investigated which macrophage subtype is responsible for modulating demyelination using M1 and M2 knockout mice. Our results indicate that M1 macrophages are key drivers of plaque formation, as infection with either HSV-IL-2 or WT HSV-1 failed to cause CNS demyelination in the absence of M1 macrophages. Conversely, M2-deficient mice exhibited demyelination, suggesting a protective role for M2 macrophages. Finally, depletion of macrophages in IL-17A-deficient mice infected with HSV-IL-2 did not restore CNS demyelination, indicating that, unlike the macrophage-FoxP3 double depletion in the HSV-IL-2 model, the IL-17A–macrophage absence is beneficial. Taken together, these findings highlight the distinct and non-redundant roles of FoxP3, IL-17A, and macrophage subsets in modulating CNS pathology during HSV-1 infection and suggest that targeting M1 macrophage activation may be a promising strategy for limiting demyelination.

Cell death regulation is essential for tissue homeostasis and its dysregulation often underlies cancer development. Understanding the different pathways of cell death can provide novel therapeutic strategies for battling cancer. This review explores several key cell death mechanisms of apoptosis, necroptosis, autophagic cell death, ferroptosis, and pyroptosis. The research gap addressed involves a thorough analysis of how these cell death pathways can be precisely targeted for cancer therapy, considering tumor heterogeneity and adaptation. It delves into genetic and epigenetic factors and signaling cascades like the phosphatidylinositol 3‐kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) and mitogen‐activated protein kinase/extracellular signal‐regulated kinase (MAPK/ERK) pathways, which are critical for the regulation of cell death. Additionally, the interaction of the microenvironment with tumor cells, and particularly the influence of hypoxia, nutrient deprivation, and immune cellular interactions, are explored. Emphasizing therapeutic strategies, this review highlights emerging modulators and inducers such as B cell lymphoma 2 (BCL2) homology domain 3 (BH3) mimetics, tumour necrosis factor‐related apoptosis‐inducing ligand (TRAIL), chloroquine, and innovative approaches to induce ferroptosis and pyroptosis. This review provides insights into cancer therapy's future direction, focusing on multifaceted approaches to influence cell death pathways and circumvent drug resistance. This examination of evolving strategies underlines the considerable clinical potential and the continuous necessity for in‐depth exploration within this scientific domain. This graphical provides a comprehensive view of therapeutic strategies for studying cell death pathways in cancer.

Manzamine A (MA), a bioactive compound derived from the marine sponge Haliclona sp., shows considerable therapeutic potential, particularly in the treatment of various cancer types. Extracted with acetone and purified through chromatography, MA exhibits a bioavailability of 20.6% when administered orally in rats, underscoring its feasibility for therapeutic use. This compound disrupts key cellular mechanisms essential for cancer progression, including microtubule dynamics and DNA replication enzymes, demonstrating strong anti-proliferative effects against multiple cancer cell lines while sparing normal cells. Additionally, network pharmacology and molecular docking studies reveal MA’s interactions with important targets related to lung cancer progression, such as EGFR and SRC, bolstering its potential as a novel anti-lung cancer agent. Pathway analyses further indicate that MA influences critical signaling pathways involved in tumor growth and metastasis. Given the urgent need for effective treatments against drug-resistant cancers and the limited toxicity profile of MA, further exploration of its pharmacological benefits and mechanism could pave the way for new therapeutic strategies in lung cancer.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) readily infects a variety of cell types impacting the function of vital organ systems, with particularly severe impact on respiratory function. Neurological symptoms, which range in severity, accompany as many as one-third of COVID-19 cases, indicating a potential vulnerability of neural cell types. To assess whether human cortical cells can be directly infected by SARS-CoV-2, we utilized stem-cell-derived cortical organoids as well as primary human cortical tissue, both from developmental and adult stages. We find significant and predominant infection in cortical astrocytes in both primary tissue and organoid cultures, with minimal infection of other cortical populations. Infected and bystander astrocytes have a corresponding increase in inflammatory gene expression, reactivity characteristics, increased cytokine and growth factor signaling, and cellular stress. Although human cortical cells, particularly astrocytes, have no observable ACE2 expression, we find high levels of coronavirus coreceptors in infected astrocytes, including CD147 and DPP4. Decreasing coreceptor abundance and activity reduces overall infection rate, and increasing expression is sufficient to promote infection. Thus, we find tropism of SARS-CoV-2 for human astrocytes resulting in inflammatory gliosis-type injury that is dependent on coronavirus coreceptors.

Background: Herbs originating from the Aconitum L. (Ranunculaceae), such as Aconitum carmichaelii Debeaux. (Wutou), Aconitum pendulum Busch. (Tiebangchui), and Aconitum kusnezoffii Reichb. (Caowu), etc. are highly valued for their medicinal properties. The roots and tubers of these herbs are commonly used to treat an array of ailments, including joint pain and tumors. The alkaloids present in them are the primary active components, with aconitine being the most notable. Aconitine has gained attention for its exceptional anti-inflammatory and analgesic properties, as well as its potential as an anti-tumor and cardiotonic agent. However, the exact process through which aconitine hinders the growth of cancerous cells and triggers their programmed cell death remains unclear. Therefore, we have undertaken a comprehensive systematic review and meta-analysis of the current research on the potential antitumor properties of aconitine. Methods: We conducted a thorough search of relevant preclinical studies in databases including PubMed, Web of Science, VIP, WanFang Data, CNKI, Embase, Cochrane Library, and National Center for Biotechnology Information (NCBI). The search was conducted up until 15 September 2022, and the data were statistically analyzed using RevMan 5.4 software. The number of tumor cell value-added, tumor cell apoptosis rate, thymus index (TI), and Bcl-2 gene expression level were the main indicators to be analyzed. Results: After applying the final inclusion criteria, a total of thirty-seven studies, comprising both in vivo and in vitro research were analyzed. The results showed that treatment with aconitine led to a significant reduction in tumor cell proliferation, a noteworthy increase in the rate of apoptosis among tumor cells, a decrease in the thymus index, and a reduction in the expression level of Bcl-2. These results suggested that aconitine could inhibit the proliferation, invasion, and migration abilities of tumor cells by regulating Bcl-2 etc., thereby enhancing the anti-tumor effects. Conclusion: In summary, our present study demonstrated that aconitine effectively reduced tumor size and volume, indicating a strong anti-tumor effect. Additionally, aconitine could increase the expression levels of caspase-3, Bax and other targets. Mechanistically, it may regulate the expression levels of Bax and Bcl-2 through the NF-κB signaling pathway, ultimately inhibiting tumor cell proliferation through autophagy.

Ellagic acid (EA), a naturally occurring polyphenolic compound, is detected in free form or linked to polyols or sugars, constituting hydrolysable tannins or ellagitannins in distinct fruits, nuts, and herbs. Today, a considerable number of botanicals and enriched foods containing EA are commercially available as nutraceuticals and used to prevent mild cognitive impairment (MCI) due to the excellent neuroprotective capacity of EA. Here, this study aims to provide an overview of the physicochemical properties, source, and pharmacokinetics of EA, and to emphasize the importance and mechanisms of EA in the prevention and management of MCI. To date, preclinical studies of EA and its derivatives in various cell lines and animal models have advanced the idea of dietary EA as a feasible agent capable of specifically targeting and improving MCI. The molecular mechanisms of EA and its derivatives to prevent or reduce MCI are mainly through reducing neuroinflammation, oxidative stress, neuronal apoptosis, synaptic dysfunction and loss, and defective mitochondrial functions. Nevertheless, well-designed and correctly large randomized controlled trials in the human population need to be performed to reinforce the scientific facticity on the beneficial effects of EA against MCI. Synchronously, the mechanism of EA against MCI is least provided cynosure and expects more attention from the emerging research community.

Mapping wall-to-wall forest aboveground biomass (AGB) at large scales is critical for understanding global climate change and the carbon cycle. In previous studies, a regression-based method was commonly used to map the spatially continuous distribution of forest AGB with the aid of optical images, which may suffer from the saturation effect. The Global Ecosystem Dynamics Investigation (GEDI) can collect forest vertical structure information with high precision on a global scale. In this study, we proposed a collaborative kriging (co-kriging) interpolation-based method for mapping spatially continuous forest AGB by integrating GEDI and Sentinel-2 data. First, by fusing spectral features from Sentinel-2 images with vertical structure features from GEDI, the optimal estimation model for footprint-level AGB was determined by comparing different machine-learning algorithms. Second, footprint-level predicted AGB was used as the main variable, with rh95 and B12 as covariates, to build a co-kriging guided interpolation model. Finally, the interpolation model was employed to map wall-to-wall forest AGB. The results showed the following: (1) For footprint-level AGB, CatBoost achieved the highest accuracy by fusing features from GEDI and Sentinel-2 data (R2 = 0.87, RMSE = 49.56 Mg/ha, rRMSE = 27.06%). (2) The mapping results based on the interpolation method exhibited relatively high accuracy and mitigated the saturation effect in areas with higher forest AGB (R2 = 0.69, RMSE = 81.56 Mg/ha, rRMSE = 40.98%, bias = −3.236 Mg/ha). The mapping result demonstrates that the proposed method based on interpolation combined with multi-source data can be a promising solution for monitoring spatially continuous forest AGB.

Rheumatoid arthritis (RA), an autoimmune disease of unknown etiology, is a serious threat to the health of middle-aged and elderly people. Although western medicine, traditional medicine such as traditional Chinese medicine, Tibetan medicine and other ethnic medicine have shown certain advantages in the diagnosis and treatment of RA, there are still some practical shortcomings, such as delayed diagnosis, improper treatment scheme and unclear drug mechanism. At present, the applications of artificial intelligence (AI)-based deep learning and cloud computing has aroused wide attention in the medical and health field, especially in screening potential active ingredients, targets and action pathways of single drugs or prescriptions in traditional medicine and optimizing disease diagnosis and treatment models. Integrated information and analysis of RA patients based on AI and medical big data will unquestionably benefit more RA patients worldwide. In this review, we mainly elaborated the application status and prospect of AI-assisted deep learning and cloud computation-oriented western medicine and traditional medicine on the diagnosis and treatment of RA in different stages. It can be predicted that with the help of AI, more pharmacological mechanisms of effective ethnic drugs against RA will be elucidated and more accurate solutions will be provided for the treatment and diagnosis of RA in the future.

We previously reported that knocking out signal peptide peptidase (SPP), a glycoprotein K (gK) binding partner, in mouse peripheral sensory neurons reduced latency-reactivation in infected mice without affecting primary virus replication or eye disease. Since virus replication in the eye plays an essential role in eye disease, we generated a conditional knockout mouse lacking SPP expression in the eye by crossing Pax6 (paired box 6)-Cre mice that have intact Pax6 expression with SPP flox/flox mice. Significantly less SPP protein expression was detected in the eyes of Pax6-SPP -/- mice than in WT control mice. HSV-1 replication in the eyes of Pax6-SPP -/- mice was significantly lower than in WT control mice. Levels of gB, gK, and ICP0 transcripts in corneas, but not trigeminal ganglia (TG), of Pax6-SPP -/- infected mice were also significantly lower than in WT mice. Corneal scarring and angiogenesis were significantly lower in Pax6-SPP -/- mice than in WT control mice, while corneal sensitivity was significantly higher in Pax6-SPP -/- mice compared with WT control mice. During acute viral infection, absence of SPP in the eye did not affect CD4 expression but did affect CD8α and IFNγ expression in the eye. However, in the absence of SPP, latency-reactivation was similar in Pax6-SPP -/- and WT control groups. Overall, our results showed that deleting SPP expression in the eyes reduced primary virus replication in the eyes, reduced CD8α and IFNγ mRNA expression, reduced eye disease and reduced angiogenesis but did not alter corneal sensitivity or latency reactivation to HSV-1 infection. Thus, blocking gK binding to SPP in the eye may have therapeutic potential by reducing both virus replication in the eye and eye disease associated with virus replication.