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The emergence of human brain organoids (hBOs) has transformed how we study brain development, disease mechanisms, and therapy discovery. These 3D in vitro neural models closely mimic the cellular diversity, spatial structure, and functional connectivity of the human brain, providing a groundbreaking platform that outperforms traditional 2D cultures and animal models in studying neurodevelopment and neurological disorders. To further explore the potential of hBOs technology, we review current literature focusing particularly on its applications for diagnosing and treating major neurological diseases such as Alzheimer’s disease, Parkinson’s disease, and other related neurological disorders. Using patient-derived induced pluripotent stem cells combined with cutting-edge gene-editing technologies, hBOs enable highly precise mechanistic studies and scalable drug screening. Moreover, we further discuss the advantages and current limitations of hBOs. Despite these challenges, hBOs remain a transformative platform for the development of targeted neurotherapeutics. Collectively, this review offers a solid foundation for advancing neuroscience research and fostering innovative treatment strategies for neurological disorders.

Colorectal cancer (CRC) is an aggressive cancer. Isoalantolactone (IATL) has been reported to exert cytotoxicity against various cancer cells, but not CRC. In this study, we explored the anti-CRC effects and mechanism of action of IATL in vitro and in vivo . Our results demonstrated that IATL inhibited proliferation by inducing G0/G1 phase cell cycle arrest, apoptosis and autophagy in CRC cells. Repression of autophagy with autophagy inhibitors chloroquine (CQ) and Bafilomycin A1 (Baf-A1) enhanced the anti-CRC effects of IATL, suggesting that IATL induces cytoprotective autophagy in CRC cells. Mechanistic studies revealed that IATL lowered protein levels of phospho-AKT (Ser473), phospho-mTOR (Ser2448), phospho-70S6K (Thr421/Ser424) in CRC cells. Inhibition of AKT and mTOR activities using LY294002 and rapamycin, respectively, potentiated the inductive effects of IATL on autophagy and cell death. In vivo studies showed that IATL suppressed HCT116 tumor growth without affecting the body weight of mice. In consistent with the in vitro results, IATL lowered protein levels of Bcl-2, Bcl-XL, phospho-AKT (Ser473), phospho-mTOR (Ser2448), and phsopho-70S6K (Thr421/Ser424), whereas upregulated protein levels of cleaved-PARP and LC3B-II in HCT116 tumors. Collectively, our results demonstrated that in addition to inhibiting proliferation, inducing G0/G1-phase cell cycle arrest and apoptosis, IATL initiates cytoprotective autophagy in CRC cells by inhibiting the AKT/mTOR signaling pathway. These findings provide an experimental basis for the evaluation of IATL as a novel medication for CRC treatment.

Methamphetamine (MA) is one of the most harmful synthetic drugs, yet the mechanisms underlying its addiction and relapse remain incompletely understood. This study investigates how cardiomyocyte-derived exosomes carrying miRNAs facilitate heart-brain crosstalk and contribute to MA dependence. A conditioned place preference (CPP) model of MA dependence was established in rats. High-throughput sequencing were employed to identify candidate miRNAs in cardiac exosomes and brain tissues. Behavioral assessments, real-time PCR, nanoparticle tracking analysis, imaging, uptake assays, network pharmacology, and dual-luciferase reporter assays were used to explore the role of cardiomyocyte-derived exosomes in MA dependence. MA induced significant CPP in rats. miR-181a-5p was markedly upregulated in cardiac exosomes and brain tissue, with higher levels observed in cardiac exosomes. biodistribution showed that cardiomyocyte-derived exosomes cross the blood-brain barrier and accumulate in the brain. uptake assays demonstrated that SH-SY5Y cells internalized these exosomes, leading to increased miR-181a-5p expression. Tail vein injections of miR-181a-5p-enriched exosomes enhanced MA CPP behavior in rats. Network pharmacology revealed 108 potential targets of miR-181a-5p, enriched in processes such as steroid biosynthesis, amide metabolism, and apoptosis, involving pathways related to the endoplasmic reticulum, MAPK signaling, and amyotrophic lateral sclerosis. Molecular docking identified stable interactions between MA and 12 targets, including HSP90B1, TNF, and MAP2K1, with miR-181a-5p binding to the 3'-UTR regions of these targets. Dual-luciferase assays confirmed the negative regulation of six targets by miR-181a-5p. This study reveals that cardiomyocyte-derived exosomes transport miR-181a-5p, facilitating heart-brain crosstalk and exacerbating MA CPP behavior in rats. These effects are mediated through the regulation of key brain targets, including HSP90B1, TNF, and MAP2K1, providing new insights into the molecular mechanisms of MA addiction and potential therapeutic targets.

Objective: To investigate the therapeutic effect of petroleum ether extract of P. aculeate Miller (PEEP) on rheumatoid arthritis (RA). Methods: In vitro : The Cell Counting Kit-8 (CCK-8) was used to detect cell activity and select the optimal concentration of the extract; the effective site was screened by nitric oxide (NO) colorimetric method and Q-PCR method; the expression of p38, p-p38, p-MK2, and Tristetraprolin (TTP) in RAW 264.7 cells were detected by Western blot. In vivo : The rat model was established by complete Freund’s adjuvant (CFA). The different doses of PEEP on CFA rats were observed with life status, paw swelling, spleen index, X-ray, Hematoxylin eosin (HE) staining; the secretion of Tumor necrosis factor α (TNF-α), interleukin-6 (IL-6) and Prostaglandin E2 (PGE 2 ) were detected by Enzyme linked immunosorbent assay (ELISA); the expressions of p38, p-p38, p-MK2, and TTP in the ankle joints of CFA rats were detected by Western blot. Result: In vitro : PEEP, Ethyl Acetate Extract of P. acul eate Miller (EEEP), N-butanol Extract of P. aculeate Miller (BEEP) have no toxic effects on RAW264.7 macrophages. PEEP, EEEP, and BEEP reduce the secretion of NO in RAW264.7 cells induced by lipopolysaccharide (LPS), only PEEP significantly inhibited the mRNA expression levels of inflammatory factors TNF-α and IL-6; PEEP-dependently reduce the secretion of TNF-α and IL-6, decrease the expression of p-p38 and p-MK2, and the level of TTP phosphorylation in LPS-induced RAW264.7 cells. In vivo : PEEP improve the living conditions of CFA rats, reduce foot swelling, spleen index, bone surface erosion and joint space narrowing; reduce the formation of synovial cells, inflammatory cells and pannus in the foot and ankle joints. PEEP reduce the secretion of TNF-α, IL-6, PGE 2 in rat serum, downregulate the expression of p-p38 and p-MK2 in the ankle joint, and reduce the phosphorylation of TTP. Conclusion: PEEP improve the living conditions of CFA rats, reduce the degree of foot swelling, protect immune organs, reduce inflammatory cell infiltration, cartilage damage, pannus formation, reduce inflammation and RA damage. The mechanism through regulating the signal pathway of p38 mitogen-activated protein kinase (p38/MAPK), which reduces the release of TNF-α, IL-6, and PGE 2 in the serum.

Circular RNAs (circRNAs) are involved in cancer development via inhibition of miRNAs, which are associated with differentiation, proliferation, migration, and carcinogenicity. Curcumin has antioxidant and anti-cancer properties, and it has also been used as a radiosensitizer. In this study, we explored the potential relationships among curcumin, circRNAs, and nasopharyngeal carcinoma (NPC). We compared the differences in circRNA levels in NPC cell lines after radiotherapy and after treatment with curcumin, using a high-throughput microarray. Further, a circRNA-miRNA-mRNA interaction network between radiation resistance NPC cell lines and tumor stem cells was constructed by applying bioinformatics. Finally, it was demonstrated by reverse transcription-quantitative polymerase chain reaction assay and wound healing assay that curcumin could enhance radiosensitization of NPC cell lines via mediating regulation of tumor stem-like cells by the \"hsa_circRNA_102115\"-\"hsa-miR-335-3p\"-\"MAPK1\" interaction network.

Sinomenine is a nonaddictive alkaloid used to prevent morphine dependence, even thoughits mechanism isnot fully understood. Astrocytes aggravate the pathological process in their neighboring cellsthrough exosomes in central nervous system diseases. However, the effect of sinomenine on astrocyte-derived exosomes for the amelioration of morphine dependence has not been reported yet. In this study, we found that sinomenine prevented the morphine-induced conditionedplace preference in mice. Sinomenine reduced the levels of cAMP and intracellular Ca2+ in morphine-treated SH-SY5Y cells. Moreover, sinomenine inhibited the expressions of p-NMDAR1/NMDAR1, p-CAMKII/CAMKII, and p-CREB/CREB in the hippocampusof morphine-dependent mice and SH-SY5Y cells. Furthermore, we found that sinomenine inhibitedthe morphine-induced activation of astrocytesin vivo and in vitro. Afterwards, exosomes were isolated from cultured primary astrocytes treated with phosphate buffer saline (PBS, ctl-exo), morphine (mor-exo), or morphine and sinomenine (Sino-exo). Subsequently, morphine-treated SH-SY5Y cells were treated with ctl-exo, mor-exo, and Sino-exo. Results showed that Sino-exo reduced the level of cAMP, intracellular Ca2+, and the expression of p-CAMKII/CAMKII and p-CREB/CREB in morphine-treated SH-SY5Y cells. In conclusion, we demonstrated that sinomenine exhibited protective effects against morphine dependencein vivo and in vitro through theNMDAR1/CAMKII/CREB pathway. Sinomenine-induced alterationof the function of astrocyte-derived exosomes may contribute to the antidependence effects of sinomenine in morphine dependence.

Ketamine is a drug of abuse worldwide and current treatments for ketamine abuse are inadequate. It is an urgent need to develop novel anti-addictive strategy. Since gut microbiota plays a crucial role in drug abuse, the present study investigates the impact and mechanisms of the gut microbiota in addictive behaviors induced by ketamine addiction. Conditioned place preference (CPP) was employed to assess addiction, followed by 16S rRNA gene sequencing to elucidate alterations in the gut microbiota. Furthermore, qRT-PCR, ELISA, and immunohistochemistry were conducted to evaluate the expression levels of crucial genes and proteins associated with the gut-brain axis. Additionally, we investigated whether ketamine addiction is regulated through the gut microbiota by orally administering antibiotics to establish pseudo-germ-free mice. We found that repeated ketamine administration (20 mg/kg) induced CPP and significantly altered gut microbiota diversity and composition, as revealed by 16S rRNA gene sequencing. Compared to the control group, ketamine exposure exhibited differences in the relative abundance of 5 microbial families, with 4 ( and ) showing increases, while one ( ) displayed a decrease. At the genus level, five genera were upregulated, while one was downregulated. Furthermore, COG analysis revealed significant differences in protein functionality between the two groups. Additionally, axis series studies showed that ketamine dependence reduced levels of tight junction proteins, GABA and GABRA1, while increasing BDNF and 5-HT. Moreover, an oral antibiotic cocktail simulating pseudo germ-free conditions in mice did not enhance the addictive behavior induced by ketamine. Our study supports the hypothesis that ketamine-induced CPP is mediated through the gut microbiota. The present study provides new insights into improvement of efficient strategy for addiction treatment.

Traditional Chinese Medicine Preparations (TCMPs) contain massive numbers of ingredients responsible for their multiple efficacies. An absorption–based quality control method for complicated TCMPs using Hu–gan–kang–yuan Capsule (HGKYC) as an example was developed. To select proper chemical markers for quality control of HGKYC, an ultra–fast liquid chromatography (UFLC) coupled with electrospray ionization quadrupole time–off light mass spectrometry (UFLC–QTOF–MS/MS) method was used for the rapid separation and structural identification of the constituents in the HGKYC extract and the rat serum after oral administration of HGKYC. As a result, one hundred and seven prototype constituents including flavonoids, organic acid, phenylpropanoids, anthraquinones, saponins, alkaloids, terpenes, phenols and amino acids in HGKYC extract, and 43 compounds found in rat serum after oral administration of HGKYC were unambiguously identified or tentatively characterized by comparing retention times and MS information with those of authentic standards or available literature references. Finally, a simple, low–cost and effective method of simultaneous determination for baicalein, wogonin, paeonol and emodin in HGKYC was developed using high performance liquid chromatography coupled with a diode array detector. In conclusion, an absorption–based quality control pattern was developed and successfully used for evaluating HGKYC.

Morphine abuse is a global public health problem. Increasing evidence has shown that gut microbiota dysbiosis plays an important role in several central nervous system diseases. However, whether there is an association between gut microbiota and morphine dependence remains unclear. In this study, the effects of isorhynchophylline on morphine dependence were evaluated based on the microbiota-gut-brain axis (MGBA). The results showed that isorhynchophylline could reverse the changes in alpha and beta diversity, composition, and richness of the intestinal flora occurring in morphine-dependent zebrafish, as well as the morphine-induced changes in the expression of MGBA-related genes in BV2 cells and the brain and intestine of zebrafish. Based on the results, we then used antibiotics to evaluate whether disrupting the gut microbiota would affect morphine addiction in zebrafish. The results showed that the antibiotic-induced intestinal floral imbalance changed the behavior of morphine-dependent zebrafish, the characteristics of the zebrafish intestinal flora, and the expression of MGBA-related genes in the zebrafish brain and intestine. Importantly, we also show that, following antibiotic administration, the ameliorative effects of isorhynchophylline on morphine addiction were lost. Together, our results indicate that the gut microbiota interacts with the brain, and dysbiosis of the intestinal flora may affect the efficacy of isorhynchophylline in the body. Our findings provide a novel framework for understanding the mechanisms of morphine addiction through the MGBA and may provide new therapeutic strategies for the use of Chinese medicines in the prevention of drug addiction.

Chinese herbal medicines have long been used to treat various illnesses by modulating the human immune response. In this study, we investigate the immuno-modulating effect and antitumor activity of Alocasia Cucullata (AC), a Chinese herb traditionally used to treat infection and cancer. We found that the whole water extract of AC roots could significantly attenuate tumor growth in mouse tumor models. The median survival time of the AC-treated mice was 43 days, 16 days longer than that of the control group. Moreover, the AC-treated mice showed substantially higher induction of key antitumor cytokines, such as IL-2, IFN-γ, and TNF-α, indicating that AC may exert antitumor effect by activating antitumor immunity. To further pinpoint the cellular and molecular mechanism of AC, we studied the dose response of a human monocytic cell line, THP-1, to the whole water extract of AC. Treatment of the AC extract significantly induced THP-1 differentiation into macrophage-like cells and the differentiated THP-1 showed expression of specific macrophage surface markers, such as CD11b and CD14, as well as productions of antitumor cytokines, e.g. IFN-γ and TNF-α. Our data thus point to AC as potentially a new, alternative immuno-modulating herbal remedy for anticancer treatment.