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Cannabis, derived from the Cannabis sativa plant, has historically been utilized for its medicinal properties, notably for pain management and symptom relief in various health conditions. Recent research has expanded its potential therapeutic applications, particularly in cancer treatment and chronic pain management. This paper explores the role of two primary cannabinoids, Delta9-tetrahydrocannabinol (THC) and cannabidiol (CBD), in addressing cancer-related symptoms and chronic pain. THC and CBD have demonstrated significant anti-tumor and anti-inflammatory activities, which are mediated through interactions with the endocannabinoid system (ECS). THC primarily targets CB1 receptors to modulate pain and neuroinflammation, while CBD exerts effects through a more complex mechanism involving various receptors, including CB2, TRPV1, and 5-HT1A. The paper reviews clinical and preclinical studies to elucidate the efficacy of these cannabinoids in alleviating symptoms such as pain, anxiety, and nausea in cancer patients and their role in enhancing traditional cancer treatments. Additionally, it addresses the potential risks and side effects associated with cannabinoid use, including cognitive and psychological effects linked to THC. The paper emphasizes the need for standardized dosing and formulation in cannabinoid therapies and calls for further research to optimize treatment protocols, assess long-term safety, and explore new therapeutic targets. The findings underscore the promising role of cannabinoids in improving the quality of life for cancer patients and managing chronic pain, highlighting their potential as adjunctive therapies in modern medicine.

Wnt signaling pathways are transmitted via 10 homologous frizzled receptors (FZD1-10) in humans. Reagents broadly inhibiting Wnt signaling pathways reduce growth and metastasis of many tumors, but their therapeutic development has been hampered by the side effect. Inhibitors targeting specific Wnt-FZD pair(s) enriched in cancer cells may reduce side effect, but the therapeutic effect of narrow-spectrum Wnt-FZD inhibitors remains to be established in vivo. Here, we developed a fragment of C. difficile toxin B (TcdBFBD), which recognizes and inhibits a subclass of FZDs, FZD1/2/7, and examined whether targeting this FZD subgroup may offer therapeutic benefits for treating breast cancer models in mice. Utilizing 2 basal-like and 1 luminal-like breast cancer models, we found that TcdBFBD reduces tumor-initiating cells and attenuates growth of basal-like mammary tumor organoids and xenografted tumors, without damaging Wnt-sensitive tissues such as bones in vivo. Furthermore, FZD1/2/7-positive cells are enriched in chemotherapy-resistant cells in both basal-like and luminal mammary tumors treated with cisplatin, and TcdBFBD synergizes strongly with cisplatin in inhibiting both tumor types. These data demonstrate the therapeutic value of narrow-spectrum Wnt signaling inhibitor in treating breast cancers.

Objective To explore the regulatory mechanism of microglia apoptosis in neuroinflammation. Methods LPS was used to establish mouse microglia cell line BV2 cells as a neuroinflammatory microglia model, IL-6 antagonist siltuximab was applied to treat LPS-induced BV2 cells. CCK-8 was used to detect the proliferation of cells. Cell apoptosis was detected by flow cytometry. ELISA kit was used to detect the content of pro-inflammatory related factors IL-6 and TNF-α. The expression of M1 polarization markers IL-1β, IFN-γ and M2 polarization markers CD206, Arg-1 in BV2 cell was detected by qRT-PCR. The expression of JAK-STAT3 signaling pathway key proteins and necroptosis related proteins RIP1 and RIP3 was detected by Western blot. Results After LPS induction, the proliferation of BV2 cells decreased, apoptosis increased, and the contents of inflammatory factors IL-6 and TNF-α increased (P＜0.01). The expression of M1 polarization markers IL-1β and IFN-γ increased, and the expression of M2 polarization markers CD206 and Arg-1 decreased(P＜0.01). The phosphorylation of JAK-STAT3 key protein increased, and the relative protein expression of RIP1 and RIP3 (P＜0.01). After treatment with IL-6 antagonist siltuximab, phosphorylation of JAK-STAT3 key proteins decreased, and RIP1 and RIP3 protein decreased (P＜0.01). Conclusions IL-6 may activate JAK-STAT3 signaling pathway to promote necroptosis of mouse microglia in neuroinflammation.

Acquired brain injury (ABI) is an injury that affects the brain structure and function. Traditional ABI treatment strategies, including medications and rehabilitation therapy, exhibit their ability to improve its impairments in cognition, emotion, and physical activity. Recently, near-infrared (NIR) photobiomodulation (PBM) has emerged as a promising physical intervention method for ABI, demonstrating that low-level light therapy can modulate cellular metabolic processes, reduce the inflammation and reactive oxygen species of ABI microenvironments, and promote neural repair and regeneration. Preclinical studies using ABI models have been carried out, revealing the potential of PBM in promoting brain injury recovery although its clinical application is still in its early stages. In this review, we first inspected the possible physical and biological mechanisms of NIR-PBM, and then reported the pathophysiology and physiology of ABI underlying NIR-PBM intervention. Therefore, the potential of NIR-PBM as a therapeutic intervention in ABI was demonstrated and it is also expected that further work can facilitate its clinical applications. [ABSTRACT FROM AUTHOR]

Human cytomegalovirus (HCMV) is a herpes virus with a long replication cycle. HCMV encoded long non-coding RNA termed RNA2.7 is the dominant transcript with a length of about 2.5kb, accounting for 25% of total viral transcripts. Studies have shown that HCMV RNA2.7 inhibits apoptosis caused by infection. The effect of RNA2.7 on other forms of cell death is still unclear. In this work, we found that RNA2.7 deletion significantly decreased the viability of HCMV-infected cells, while treatment with ferroptosis inhibitor Fer-1 rescued the infection-induced cell death, demonstrating an anti-ferroptosis role of RNA2.7. The results further showed that RNA2.7 inhibited ferroptosis via enhancing Ferritin Heavy Chain 1 (FTH1) and Solute Carrier Family 7 Member 11 (SLC7A11) expression in Erastin treated cells without involving other viral components. Pooled Genome-wide CRISPR screening revealed zinc finger protein 395 (ZNF395) as a new regulator repressing the expression of FTH1 and SLC7A11. HCMV RNA2.7 promoted proteasome-mediated degradation of ZNF395 that resulted in upregulation of FTH1 and SLC7A11 to inhibit ferroptosis, therefore maintain survival in host cells and complete replication of virus. Author summary: Human cytomegalovirus (HCMV) exhibits a latency that persists throughout life following the primary infection. Approximately 0.6% of newborns are HCMV-congenitally infected, 20–25% of which are symptomatic at birth or will develop long-term sequelae with a substantial public health impact. HCMV is slow-replicating virus that maintains the survival of the host cell to ensure virus replication. Several HCMV encoded proteins have been found to inhibit apoptosis and necroptosis following viral infection. However, the role of HCMV in other types of programmed cell death such as ferroptosis has not been clarified. In this study, we found that HCMV RNA2.7 inhibited ferroptosis independent on other viral components. Then we tried to explore how RNA2.7 inhibit ferroptosis and found RNA2.7 effectively increased ferritin and GSH contents to dampen ferroptosis. However, the regulation of RNA2.7 on ferritin and GSH contents was not depend on any previously reported regulators. Therefore, a pooled genome-wide CRISPR was employed and ZNF395 was determined as a newly regulator that promoted ferroptosis. Then, we confirmed that HCMV RNA2.7 promoted proteasome-mediated degradation of ZNF395 that resulted in upregulation of FTH1 and SLC7A11 to inhibit ferroptosis, therefore maintain survival in host cells and complete replication of virus. [ABSTRACT FROM AUTHOR]

In this paper, a joint scheduling method of peak shaving and frequency regulation using hybrid energy storage system considering degeneration characteristic is proposed. Firstly, incorporating degradation costs of the hybrid energy storage system with respect to the depth of discharge and cycle lifetime, long‐term costs of battery energy storage and flywheel energy storage are modelled and transformed to short‐term costs related to real‐time operation. Then, a joint scheduling model is proposed for hybrid energy storage system to perform peak shaving and frequency regulation services to coordinate and optimize the output strategies of battery energy storage and flywheel energy storage, and minimize the total operation cost of microgrid. In addition, three optimal dispatching strategies for hybrid energy storage system to participate in the auxiliary service of power grid are proposed based on the established auxiliary service model. Simulation studies demonstrate that the proposed joint scheduling method can optimize the power of different energy storage, alleviate the degradation process of battery energy storage. Compared with the scenario without scheduling hybrid energy storage system, scheduling hybrid energy storage system can reduce the total operation cost, and the electricity cost of microgrid is reduced by 13.13%. [ABSTRACT FROM AUTHOR]

The eukaryotic ribosome is a large ribonucleoprotein complex consisting of four types of ribosomal RNA (rRNA) and approximately 80 ribosomal proteins (RPs), forming the 40S and 60S subunits. In all living cells, its primary function is to produce proteins by converting messenger RNA (mRNA) into polypeptides. In addition to their canonical role in protein synthesis, RPs are crucial in controlling vital cellular processes such as cell cycle progression, cellular proliferation, differentiation, DNA damage repair, genome structure maintenance, and the cellular stress response. Viruses, as obligate intracellular parasites, depend completely on the machinery of the host cell for their replication and survival. During viral infection, RPs have been demonstrated to perform a variety of extra-ribosomal activities, which are especially important in viral disease processes. These functions cover a wide range of activities, ranging from controlling inflammatory responses and antiviral immunity to promoting viral replication and increasing viral pathogenicity. Deciphering the regulatory mechanisms used by RPs in response to viral infections has greatly expanded our understanding of their functions outside of the ribosome. Furthermore, these findings highlight the promising role of RPs as targets for the advancement of antiviral therapies and the development of novel antiviral approaches. This review comprehensively examines the many functions of RPs outside of the ribosome during viral infections and provides a foundation for future research on the host–virus interaction. [ABSTRACT FROM AUTHOR]

Background: Attention deficits are notable in Lewy body dementia (LBD) and in Alzheimer's disease (AD). In this study, we combined functional magnetic resonance imaging (fMRI) and electroencephalograph (EEG) to detect neural correlates of attention dysfunctions in LBD and AD. Methods: We recruited 33 patients with LBD, 15 patients with AD and 19 elderly healthy controls. The participants performed the modified Attention Network Task (ANT) to investigate the attention dysfunctions. Results: We found that LBD had alerting attention deficits and AD showed apparent orienting attention dysfunctions, while LBD and AD maintained relatively normal executive/conflict attention. Based on source-level EEG analyses, LBD had frontal-central deficits for alerting attention while AD showed inferior frontal and precentral impairments for orienting attention. In addition, the insular and inferior frontal areas were hyper-activated in LBD and AD for executive/conflict attention. Apart from these areas, LBD showed activity in the complementary temporal-central-occipital network for the modified ANT task. Furthermore, the oscillational sources for the ANT effects indicated that the alpha and theta bands were partly impaired in dementia patients. Conclusions: In summary, using source-localised EEG, we found that attention dysfunctions in LBD and AD engaged different neural networks. [ABSTRACT FROM AUTHOR]

This study aims to understand and address the health education needs of family caregivers of people living with epilepsy, irrespective of the patient's age. It seeks to construct and implement a targeted health education program informed by empowerment education theory and evaluate its effectiveness. Methods: Through semi-structured interviews, we explored the diverse health education needs of family caregivers of people with epilepsy, identifying key themes and constructing a responsive health education plan. The program's effectiveness was assessed through a quasi-experimental study. The control group received routine health education, while the intervention group participated in an empowerment-based education program in addition to the standard protocol. We evaluated changes in caregivers' disease management capabilities, knowledge about epilepsy, and quality of life at baseline, one month, and three months post-intervention using appropriate statistical analyses to confirm significance. Results: Sixty-five family caregivers participated, with 32 in the intervention group and 33 in the control group. Guided by phenomenological research, four main themes were identified. Significant improvements in disease management, epilepsy knowledge, and quality of life were observed in the intervention group, exceeding those in the control group at both follow-up intervals (p< 0.05). Conclusion: An empowerment-based health education program significantly enhances caregivers' competencies across age groups in managing epilepsy, underscoring its effectiveness as an intervention model. [ABSTRACT FROM AUTHOR]

This study looked at how desalinated seawater, which has low minerals and high boron, could affect bone health. Prior research suggests that low mineral water may harm bone health and boron could be beneficial, but the overall impact on bone health is still unclear. Eighty-nine-week-old male Balb/C mice were allocated into eight groups and administered either tap water or purified water with varying boron concentrations (0, 5, 40, and 200 mg/L). They were kept in an environment mimicking tropical conditions (35–40 °C, 70–80% humidity) and underwent daily treadmill exercise for 13 weeks. At the 14th week, serum, femora, and lumbar vertebrae were collected for mineral metabolism, bone biomarker, microstructure, and biomechanics evaluation. Boron exposure improved bone formation, microstructure, and biomechanics initially but the benefits weakened with higher levels of exposure (p < 0.05). Co-exposure to purified water elevated serum boron but weakened the promotion of boron on bone minerals and the bone benefits of boron compared to tap water (p < 0.05). Thus, when studying the health effects of boron in desalinated seawater, it is crucial to look at various health effects beyond bone health. Furthermore, it is important to consider the mineral composition of drinking water when using boron for bone health benefits. [ABSTRACT FROM AUTHOR]