Using Patient-Derived Induced Pluripotent Stem Cells to Model and Treat Epilepsies.

Human induced pluripotent stem cells (iPSCs) are transforming the fields of disease modeling and precision therapy. For the treatment of neurological disorders, iPSCs introduce the possibility for targeted cell-based therapies by deriving patient-specific neural tissue in vitro that may ultimately be used for transplantation. We review iPSC technologies and their applications that have already advanced our understanding of neurological disorders, focusing on the epilepsies. We also discuss the application of powerful new tools such as genome editing and multi-well, multi-electrode array recording platforms to iPSC disease modeling and therapy development for the epilepsies. Despite some limitations, the field of iPSCs is evolving rapidly and is quickly becoming vital for understanding mechanisms of genetic epilepsies and for future patient-specific therapeutic applications.

Enhancing treatment of lumbar disc herniation with Erxian decoction and auricular acupoint pressure: A randomized controlled trial.

OBJECTIVE: The incidence of lumbar disc herniation (LDH) is on the rise annually, with an emerging trend of affecting younger age groups. This study aims to investigate the clinical effectiveness of combining Erxian decoction with auricular acupoint pressure therapy in treating LDH. Our objective is to furnish evidence supporting the incorporation of traditional Chinese medicine (TCM) rehabilitation techniques in clinical settings. METHODS: This randomized controlled trial enrolled 102 patients diagnosed with LDH and allocated them into Control and Intervention groups. The Control group underwent a 2-week rehabilitation regimen, whereas the Intervention group received an augmented treatment comprising Erxian decoction along with auricular acupoint pressure therapy based on the Control group. Main outcome measures included 3 scales - visual analog scale (VAS), Japanese Orthopedic Association (JOA), and Oswestry Disability Index - as well as 3 inflammatory markers: C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α). Additionally, pressure pain threshold and pain tolerance threshold values were evaluated. Participants were assessed at baseline, on 14-day, and on 28-day posttreatment. RESULTS: After 2 weeks of treatment, both the Control and Intervention groups exhibited significant improvements in the VAS, JOA, ODI, CRP, IL-6, TNF-α, pressure pain threshold, and pain tolerance threshold (P < .05). These improvements persisted at the 28-day in the VAS, JOA, and ODI scores (P < .05). On 14-day, the Intervention group showed significantly better outcomes compared to the Control group in terms of the VAS, JOA, ODI, CRP, TNF-α, and pressure pain threshold (P < .05). CONCLUSION: Compared to conventional rehabilitation therapy, the combination of Erxian decoction and auricular acupoint pressure therapy demonstrates clear benefits in alleviating symptoms in patients with LDH. This approach offers fresh perspectives and substantiates evidence for future treatment strategies in managing LDH.

The experiences of Chinese colorectal cancer survivors in marital intimacy after ostomy creation: A qualitative study.

Background: Colorectal cancer (CRC) ranks as the third most prevalent cancer globally. The disease and its treatment significantly impact marital intimacy, particularly among individuals who have undergone ostomy creation. Therefore, it is necessary to explore their experiences. Objective: This study aimed to explore the experiences of colorectal cancer survivors in marital intimacy after ostomy creation and clarify the domain and sub-domain of marital intimacy in CRC survivors with ostomy. Method: This study used a qualitative descriptive design, and participants were selected by purposive sampling from two hospitals in Henan province, China. Sixteen patients participated in this research, and the data were collected through an in-depth interview from June 27 to September 27, 2023. Colaizzi's method was used to analyze the data. Results: Five themes emerged from data analysis, including physical intimacy, psychological intimacy, social intimacy, spiritual intimacy, and operational intimacy. Conclusion: By profiling the experiences of CRC survivors in marital intimacy after ostomy creation, the domain and sub-domain of marital intimacy were clarified in this cohort and revealed that ostomy had a severe effect on marital intimacy among colorectal cancer survivors. The results from this study could be used by nurses, midwives, and other healthcare professionals to design specific interventions covering all aspects of marital intimacy. Also, the findings will guide the development of a particular instrument for marital intimacy in CRC survivors with ostomy.

Challenges Threatening Agricultural Sustainability in Central Asia: Status and Prospect.

Agriculture provides humanity with the most basic products to sustain life and raw materials for production, closely linking human society and nature together. The sustainable development of agriculture, an inevitable choice to maintain long-term social stability, steady economic growth, and ecological security, is the key to the coordinated development of the economy, society, and environment in developing Central Asia economies. We attempted to evaluate the trend of agricultural sustainability in Central Asia between 2002 and 2017 by adopting analytic hierarchy process and entropy weight method in this study. It was found that the overall sustainability level of regional agriculture is rising, which is mainly driven by economic progress, with social and ecological dimensions contributing much less. Accordingly, we advanced four suggestions: enhancing water productivity, optimizing planting techniques, improving agricultural cooperatives, and promoting digital land management to boost the agricultural sustainability of the region.

Status and Prospect of Ecological Environment in the Belt and Road Initiative Regions.

With the widespread recognition and in-depth implementation of the Belt and Road Initiative (BRI), especially in the context of global climate change, the ecological environment of Belt and Road Initiative regions might be confronted with pressures and challenges with rapid socioeconomic development. In response to those potential environmental challenges, China has put forward Green BRI and enriched the new Silk Road with more environmental connotations, aiming to reduce the conflict between economic development and eco-environmental protection. Currently, there is a lack of systematic and holistic research on eco-environmental issues in BRI regions. In addition, feasible solutions to enhance BRI's contribution to the eco-environment remain insufficient. Having systematically reviewed the relevant literature on the eco-environment in BRI regions, we found that most regions along the BRI routes are in sensitive zones of climate and geological change, with fragile eco-environments and strong vulnerability to climate change, natural disasters and human activities. The main eco-environment status of the BRI regions is as follows: (1) The total water resources in BRI regions account for only 36% of the global total, with uneven distribution and complex spatial precipitation, posing higher pressure on water security. (2) Vegetation varies significantly from region to region. The vegetation in South Asia is the richest, with its mean annual NDVI exceeding 0.7. The NDVI in East Europe, Russia and South China are between 0.4 and 0.7, and that in Central Asia and West Asia are below 0.2. (3) The BRI regions are abundantly blessed with natural resources, with the total recoverable oil reserves, natural gas reserves and the total mining area reaching 66%, 65.5% and 42.31% of the world's total, respectively, but severe overexploitation and overconsumption of those resources degrade their eco-environment. Accordingly, future research directions, such as target on integrated, interdisciplinary and coordinated studies on eco-environmental issues in BRI regions, are proposed in this paper to achieve optimization of BRI's contribution to eco-environment protection in BRI regions.

Ecosystem Health and Environmental Geography in the Belt and Road Regions.

The "Belt and Road" Initiative (BRI), i.e., the official Chinese term for the "Silk Road Economic Belt" and the "21st Century Maritime Silk Road", was proposed to share China's development opportunities with BRI-related countries and achieve common prosperity. Though the BRI itself conveys rich social and economic connotations, ecosystem health and the environmental problems in the Belt and Road regions are scientific issues. In this study, papers relating to the ecological issues of the BRI between January 2013 and December 2021 were collected and analyzed via CiteSpace. We found that some ecological issues were involved with the environmental challenges posed by the BRI, whereas others were, to a certain extent, subjective assumptions. Accordingly, we identified and classified the limitations and constraints of those environmental views about the BRI. By emphasizing that scientific data is key to explaining the ecological problems, we advanced four prospects for ecosystem health and environmental geography studies in the Belt and Road regions: (1) Spatial analysis and monitoring technology for the environment; (2) Clarification of the characteristics and mechanisms of the ecosystem and environments; (3) A focus on the interaction between the economy and the environment; (4) Specific and targeted strategies and solutions to different environmental problems.

The correlation between intimate relationship, self-disclosure, and adaptability among colorectal cancer enterostomy patients.

ABSTRACT: The postoperative physiological changes and psychological pressure of cancer patients affect the patient's adaptability to the disease, and thus affect the spousal intimate relationship. This study aimed to evaluate the correlation between spousal intimate relationship, self-disclosure, and adaptability among colorectal cancer (CCI) patients with enteric stoma.This cross-sectional study selected patients with CCI in Henan Province from February 2018 to October 2020. The Marital Adjustment Test (MAT), the Distress Disclosure Index scale, and the Ostomy adjustment inventory-20 scale were used to collect relevant data of the participants. A Pearson correlation analysis was used to test the correlation between variables, and multiple stepwise regression analysis was used to test the influence of general information on the intimate relationship, self-disclosure, and adaptability.Among the respondents, 42.6% had a spousal intimate relationship problem, 58.4% had a low or moderate level of self-disclosure, and 90.8% were at a low or moderate level of adaptation. Education background, self-care ability, and postoperative time were associated with a couple's intimate relationship. Average monthly household income, gender, and place of residence were associated with self-disclosure. Self-care ability, average monthly household income, postoperative time, and educational background were associated with adaptation.Healthcare workers should provide more health education training to guide CCI enterostomy patients to express their thoughts and feelings with each other increase self-disclosure, so as to enhance their intimate relationship then improve their adoption to ostomy, finally elevate their quality of life.

Gut microbial bile acid metabolite skews macrophage polarization and contributes to high-fat diet-induced colonic inflammation.

High-fat diet (HFD) leads to systemic low-grade inflammation, which has been involved in the pathogenesis of diverse metabolic and inflammatory diseases. Colon is thought to be the first organ suffering from inflammation under HFD conditions due to the pro-inflammatory macrophages infiltration, however, the mechanisms concerning the induction of pro-inflammatory phenotype of colonic macrophages remains unclear. In this study, we show that HFD increased the percentage of gram-positive bacteria, especially genus Clostridium, and resulted in the significant increment of fecal deoxycholic acid (DCA), a gut microbial metabolite produced by bacteria mainly restricted to genus Clostridium. Notably, reducing gram-positive bacteria with vancomycin diminished fecal DCA and profoundly alleviated pro-inflammatory macrophage infiltration in colon, whereas DCA-supplemented feedings to vancomycin-treated mice provoked obvious pro-inflammatory macrophage infiltration and colonic inflammation. Meanwhile, intra-peritoneal administration of DCA also elicited considerable recruitment of macrophages with pro-inflammatory phenotype. Mechanistically, DCA dose-dependently promoted M1 macrophage polarization and pro-inflammatory cytokines production at least partially through toll-like receptor 2 (TLR2) transactivated by M2 muscarinic acetylcholine receptor (M2-mAchR)/Src pathway. In addition, M2-mAchR mediated increase of TLR2 transcription was mainly achieved via targeting AP-1 transcription factor. Moreover, NF-κB/ERK/JNK signalings downstream of TLR2 are involved in the DCA-induced macrophage polarization. In conclusion, our findings revealed that high level DCA induced by HFD may serve as an initiator to activate macrophages and drive colonic inflammation, thus offer a mechanistic basis that modulation of gut microbiota or intervening specific bile acid receptor signaling could be potential therapeutic approaches for HFD-related inflammatory diseases.

Deoxycholic Acid-Mediated Sphingosine-1-Phosphate Receptor 2 Signaling Exacerbates DSS-Induced Colitis through Promoting Cathepsin B Release.

We recently have proved that excessive fecal DCA caused by high-fat diet may serve as an endogenous danger-associated molecular pattern to activate NLRP3 inflammasome and thus contributes to the development of inflammatory bowel disease (IBD). Moreover, the effect of DCA on inflammasome activation is mainly mediated through bile acid receptor sphingosine-1-phosphate receptor 2 (S1PR2); however, the intermediate process remains unclear. Here, we sought to explore the detailed molecular mechanism involved and examine the effect of S1PR2 blockage in a colitis mouse model. In this study, we found that DCA could dose dependently upregulate S1PR2 expression. Meanwhile, DCA-induced NLRP3 inflammasome activation is at least partially achieved through stimulating extracellular regulated protein kinases (ERK) signaling pathway downstream of S1PR2 followed by promoting of lysosomal cathepsin B release. DCA enema significantly aggravated DSS-induced colitis in mice and S1PR2 inhibitor as well as inflammasome inhibition by cathepsin B antagonist substantially reducing the mature IL-1ß production and alleviated colonic inflammation superimposed by DCA. Therefore, our findings suggest that S1PR2/ERK1/2/cathepsin B signaling plays a critical role in triggering inflammasome activation by DCA and S1PR2 may represent a new potential therapeutic target for the management of intestinal inflammation in individuals on a high-fat diet.

Curcumin alleviates DSS-induced colitis via inhibiting NLRP3 inflammsome activation and IL-1ß production.

BACKGROUND: NLRP3 inflammasome mediates IL-1ß maturation, therefore plays a vital role in the development of IBD. Curcumin is known for possessing strong anti-inflammatory property. OBJECTIVE: The present study was to investigate the protective effects of curcumin on dextran sulfate sodium (DSS)-induced colitis through inhibiting NLRP3 inflammasome activation and IL-1ß production. METHODS: LPS-primed macrophages were treated with curcumin prior to DSS triggering NLRP3 inflammasome activation, IL-1ß secretion and ASC oligomerization were observed. The mechanisms of curcumin in the inhibition of DSS-induced inflammasome activation were explored. Curcumin or caspase-1/NLRP3 inhibitor was administrated respectively in DSS-induced colitis mouse model. The changes of body weight, disease activity index, colon length were measured. Additionally, mature IL-1ß and other inflammatory cytokines, MPO activity and histopathological damage were analyzed for the evaluation of colitis severity. RESULTS: NLRP3 inflammasome activation was dramatically inhibited by curcumin in DSS-stimulated macrophages, as evidenced by decreased IL-1ß secretion, less caspase-1 activation and ASC specks. Mechanistically, curcumin prevented DSS-induced K+ efflux, intracellular ROS formation and cathepsin B release, three major cellular events mediating NLRP3 inflammasome activation. In DSS-induced colitis, curcumin administration significantly ameliorated colitis symptoms by reducing weight loss, DAI and colon length shortening. Meanwhile, curcumin significantly decreased the expression of multiple inflammatory cytokines (including mature IL-1ß, IL-6, MCP-1), MPO activity, caspase-1 activity as well as histopathological damage. Furthermore, blockage of NLRP3 inflammasome activation in vivo with specific NLRP3 inhibitor abrogated the further inhibitory effect of curcumin on DSS-induced colitis. CONCLUSION: Curcumin could strongly suppress DSS-induced NLRP3 inflammsome activation and alleviate DSS-induced colitis in mice, thus it may be a promising candidate drug in clinical application for IBD therapy.