Exploring the Therapeutic Potential of Baicalin: Mitigating Anxiety and Depression in Epileptic Rats.

BACKGROUND: Epilepsy is a serious neurological disorder that affects millions of people each year, often leading to cognitive issues and reduced quality of life. Medication is the main treatment, but many patients experience negative side effects. Male Sprague-Dawley (SD) rats were chosen as experimental animals for this experiment due to their physiological and genetic similarities to humans, cost-effectiveness, and ease of handling in a laboratory setting. AIMS: The objective of this study was to assess the neuroprotective properties of baicalin (BA) in relation to its impact on anxiety and depressive-like behaviors in the epilepsy model. METHODS: Thirty male Sprague-Dawley (SD) rats were selected for this experiment. Pentylenetetrazol (PTZ) kindling (40 mg/kg; i.p.) was utilized to establish an epilepsy model. The effect of BA (50 mg/kg; gavage) on seizure severity (assessed using the Racine scale), anxiety, and depressive- like behaviors (evaluated through open field experiments and forced swimming tests) was examined. Histological examinations, including hematoxylin and eosin (HE) staining and Nissl staining, were conducted to assess neuronal damage. Furthermore, the neuroprotective properties of BA were examined through the analysis of Doublecortin (DCX), MKI67 (KI67), and Brain-Derived Neurotrophic Factor (BDNF) levels in the hippocampus of rats. The inhibitory impact of BA on neuroinflammation was assessed via dual labeling for NOD-like receptor thermal protein domain associated protein 3 (NLRP3) and the microglial marker ionized calcium- binding adapter molecule 1 (Iba-1). The influence of BA on the expression of P2X7 receptor (P2X7R), NLRP3, and Interleukin-1ß (IL-1ß) was also assessed by reverse transcription quantitative PCR (RT-qPCR) in the brain. Finally, we employed a molecular docking model to assess the extent of receptor-ligand binding. RESULTS: Epilepsy models exhibited significant anxiety and depressive-like behaviors, and BA significantly reduced the severity of seizures in these rats while also alleviating their anxiety and depressive-like behaviors. Moreover, neuronal loss and damage were observed in the hippocampus of epileptic rats, but BA was able to effectively counteract this issue by enhancing BDNF expression and promoting neurogenesis within the hippocampus, especially in the DG region. The co-localization of Iba-1 with NLRP3 indicated the activation of NLRP3 inflammasome in microglia. Subsequent RT-PCR revealed that BA may alleviate anxiety and depressive-like behaviors in epileptic rats by activating the P2RX7/NLRP3/ IL-1ß signaling pathway. The final molecular docking results indicated that BA had a good binding affinity with proteins, such as P2RX7, NLRP3, and IL-1ß. CONCLUSION: This study confirmed the effectiveness of BA in improving anxiety and depressivelike behaviors associated with epilepsy. Moreover, it provides theoretical support for the neuroprotective role demonstrated by BA.

Development and Assessment of a Prediction Model for Alzheimer's Disease Diagnosis Based on Thermoregulation-Related Genes.

BACKGROUND: Alzheimer's disease (AD) is a prevalent neurodegenerative condition among the elderly population and the most common form of dementia, however, we lack potent interventions to arrest its inherent pathogenic vectors. Robust evidence indicates thermoregulatory perturbations during and before the onset of symptoms. Therefore, temperature-regulated biomarkers may offer clues to therapeutic targets during the presymptomatic stage. OBJECTIVE: The purpose of this study is to develop and assess a thermoregulation-related gene prediction model for Alzheimer's Disease diagnosis. METHOD: This study aims to utilize microarray bioinformatic analysis to identify the potential biomarkers of AD by analyzing four microarray datasets (GSE48350, GSE5281, GSE122063, and GSE181279) of AD patients. Furthermore, thermoregulation-associated hub genes were identified, and the expression patterns in the brain were explored. In addition, we explored the infiltration of immune cells with thermoregulation-related hub genes. Diagnostic marker validation was then performed at the single-cell level. Finally, the prediction of targeted drugs was performed based on the hub genes. RESULTS: Through the analysis of four datasets pertaining to AD, a total of five genes associated with temperature regulation were identified. Notably, CCK, CXCR4, SLC27A4, and SLC17A6 emerged as diagnostic markers indicative of AD-related brain injury. Furthermore, in the examination of peripheral blood samples from AD patients, SLC27A4 and CXCR4 were identified as pivotal diagnostic indicators. Regrettably, animal experimentation was not pursued to validate the data; rather, an assessment of temperature regulation-related genes was conducted. Future investigations will be undertaken to establish the correlation between these genes and AD pathology. CONCLUSION: Overall, CCK, CXCR4, SLC27A4, and SLC17A6 can be considered pivotal biomarkers for diagnosing the pathogenesis and molecular functions of AD.

Effect of electroacupuncture at "Neiguan" (PC6) on pain and brain orexin 1 receptor in mice with inflammatory pain. / 电针"å† å ³"å¯¹ç‚Žæ€§ç—›å°é¼ è„‘å† é£Ÿæ¬²ç´ 1受体的影响.

OBJECTIVES: To observe the effect of electroacupuncture (EA) at "Neiguan" (PC6) on pain response in mice injected with complete Freund's adjuvant (CFA) in the hind paw, so as to investigate the mechanism of orexin 1 receptor (OX1R) -endogenous cannabinoid 1 receptor (CB1R) pathway in acupuncture analgesia. METHODS: A total of 48 male C57BL/6 mice were used in the present study. In the first part of this study, 18 mice were randomized into control, model and EA groups, with 6 mice in each group. In the second part of this study, 30 mice were randomized into control, model, EA, EA+Naloxone, EA+OX1R antagonist (SB33486) groups, with 6 mice in each group. Inflammatory pain model was established by subcutaneous injection of 20 µL CFA solution in the left hind paw. EA (2 Hz, 2 mA ) was applied to bilateral PC6 for 20 min, once a day for 5 consecutive days. The mice in the EA+Naloxone and EA+SB33486 groups were intraperitoneally injected with naloxone (10 mg/kg) or SB33486 (15 mg/kg) 15 min before EA intervention on day 5, respectively. Tail-flick method and Von Frey method were used to detect the thermal pain threshold and mechanical pain threshold of mice. Quantitative real-time PCR was used to detect the expression level of ß-endorphin mRNA in periaqueductal gray (PAG) of mice. The expression of OX1R positive cells in the lateral hypothalamic area (LH) and CB1R positive cells in the ventrolateral periaqueductal gray (vlPAG) were detected by immunofluorescence. RESULTS: Compared with the control group, the thermal pain threshold and mechanical pain threshold of the model group were decreased (P<0.001), the expression level of ß-endorphin mRNA in PAG was decreased (P<0.001), and the numbers of OX1R positive cells in LH and CB1R positive cells in vlPAG were decreased (P<0.05, P<0.001). Compared with the model group, the thermal pain threshold and mechanical pain threshold of the EA group were significantly increased (P<0.001), and the numbers of OX1R positive cells in LH and CB1R positive cells in vlPAG were increased (P<0.01, P<0.001). Compared with the EA group, the mechanical pain threshold in the EA+SB33486 group was significantly decreased (P<0.01), but there was no significant difference in the mechanical pain threshold between the EA+Naloxone group and EA group, and the numbers of OX1R positive neurons in LH and CB1R positive neurons in vlPAG were decreased in the EA+SB33486 group (P<0.001). CONCLUSIONS: EA at PC6 can achieve analgesic effect on CFA mice by activating the OX1R-CB1R pathway in the brain, and this effect is opioid-independent.

Hydrogel loaded with thiolated chitosan modified taxifolin liposome promotes osteoblast proliferation and regulates Wnt signaling pathway to repair rat skull defects.

To alleviate skull defects and enhance the biological activity of taxifolin, this study utilized the thin-film dispersion method to prepare paclitaxel liposomes (TL). Thiolated chitosan (CSSH)-modified TL (CTL) was synthesized through charge interactions. Injectable hydrogels (BLG) were then prepared as hydrogel scaffolds loaded with TAX (TG), TL (TLG), and CTL (CTLG) using a Schiff base reaction involving oxidized dextran and carboxymethyl chitosan. The study investigated the bone reparative properties of CTLG through molecular docking, western blot techniques, and transcriptome analysis. The particle sizes of CTL were measured at 248.90 ± 14.03 nm, respectively, with zeta potentials of +36.68 ± 5.43 mV, respectively. CTLG showed excellent antioxidant capacity in vitro. It also has a good inhibitory effect on Escherichia coli and Staphylococcus aureus, with inhibition rates of 93.88 ± 1.59 % and 88.56 ± 2.83 % respectively. The results of 5-ethynyl-2 '-deoxyuridine staining, alkaline phosphatase staining and alizarin red staining showed that CTLG also had the potential to promote the proliferation and differentiation of mouse embryonic osteoblasts (MC3T3-E1). The study revealed that CTLG enhances the expression of osteogenic proteins by regulating the Wnt signaling pathway, shedding light on the potential application of TAX and bone regeneration mechanisms.

Heterogeneous changes in gut and tumor microbiota in patients with pancreatic cancer: insights from clinical evidence.

BACKGROUND: Pancreatic cancer is the foremost contributor to cancer-related deaths globally, and its prevalence continues to rise annually. Nevertheless, the underlying mechanisms behind its development remain unclear and necessitate comprehensive investigation. METHODS: In this study, a total of 29 fresh stool samples were collected from patients diagnosed with pancreatic cancer. The gut microbial data of healthy controls were obtained from the SRA database (SRA data number: SRP150089). Additionally, 28 serum samples and diseased tissues were collected from 14 patients with confirmed pancreatic cancer and 14 patients with chronic pancreatitis. Informed consent was obtained from both groups of patients. Microbial sequencing was performed using 16s rRNA. RESULTS: The results showed that compared with healthy controls, the species abundance index of intestinal flora in patients with pancreatic cancer was increased (P < 0.05), and the number of beneficial bacteria at the genus level was reduced (P < 0.05). Compared with patients with chronic pancreatitis, the expression levels of CA242 and CA199 in the serum of patients with pancreatic cancer were increased (P < 0.05). The bacterial richness index of tumor microorganisms in patients with pancreatic cancer increased, while the diversity index decreased(P < 0.05). Furthermore, there was a change in the species composition at the genus level. Additionally, the expression level of CA242 was found to be significantly positively correlated with the relative abundance of Acinetobacter(P < 0.05). CONCLUSION: Over all, the expression levels of serum tumor markers CA242 and CA19-9 in patients with pancreatic cancer are increased, while the beneficial bacteria in the intestine and tumor microenvironment are reduced and pathogenic bacteria are increased. Acinetobacter is a specific bacterial genus highly expressed in pancreatic cancer tissue.

Metabolic Heterogeneity and Potential Immunotherapeutic Responses Revealed by Single-Cell Transcriptomics of Breast Cancer.

BACKGROUND: Breast cancer (BC) exhibits remarkable heterogeneity. However, the transcriptomic heterogeneity of BC at the single-cell level has not been fully elucidated. METHODS: We acquired BC samples from 14 patients. Single-cell RNA sequencing (scRNA-seq), bioinformatic analyses, along with immunohistochemistry (IHC) and immunofluorescence (IF) assays were carried out. RESULTS: According to the scRNA-seq results, 10 different cell types were identified. We found that Cancer-Associated Fibroblasts (CAFs) exhibited distinct biological functions and may promote resistance to therapy. Metabolic analysis of tumor cells revealed heterogeneity in glycolysis, gluconeogenesis, and fatty acid synthetase reprogramming, which led to chemotherapy resistance. Furthermore, patients with multiple metastases and progression were predicted to benefit from immunotherapy based on a heterogeneity analysis of T cells and tumor cells. CONCLUSIONS: Our findings provide a comprehensive understanding of the heterogeneity of BC, provide comprehensive insight into the correlation between cancer metabolism and chemotherapy resistance, and enable the prediction of immunotherapy responses based on T-cell heterogeneity.

Safety assessment of Acori Tatarinowii Rhizoma: acute and subacute oral toxicity.

Introduction: Acori Tatarinowii Rhizoma (ATR) is a well-known traditional Chinese medicine that is used for treating neuropathic diseases. However, there is little information about the safety of ATR. Methods: The present study evaluated the acute and subacute oral toxicity of a water extract of ATR in Institute of Cancer Research (ICR) mice. In acute trials, a single administration of extract at a dose 5,000 mg/kg body weight led to no clinical signs of toxicity or mortality, indicating that the lethal dose (LD50) exceeded 5,000 mg/kg. A subacute toxicity test was done using daily doses of 1,250, 2,500, and 5,000 mg/kg of the ATR extract for 28 days, which did not show any adverse clinical symptoms or mortality. However, the male renal organ index and urea level in mice given 5,000 mg/kg was obviously abnormal, which was consistent with pathological results and suggested that this dose might cause kidney injury. Results: Doses of ATR lower than 2,500 mg/kg could be regarded as safe, although the potential cumulative effects of long-term use of high doses of ATR need to be considered. Discussion: The study highlights the function of ATR in reducing blood lipids and provides a new idea for its widespread clinical use in the future.

Interpersonal Problem Profiles of Personality and Psychopathology Constructs in Chinese Undergraduates and Offenders.

The interpersonal problem circumplex is extensively used in the field as an assessment framework for understanding the interpersonal implications of a range of personality and psychopathology constructs. The vast majority of this large literature has been conducted in Western convenience and clinical samples. We computed interpersonal problem structural summary parameters for a range of personality and psychopathology variables in two Chinese offender samples (N = 424 and N = 555) and one undergraduate sample (N = 511) to test how well findings from Western samples generalize to Chinese undergraduates and offenders. The results showed that findings in Western samples generalized reasonably well to Chinese young adult and forensic contexts, although the interpersonal profiles of external variables were less specific in Chinese samples. Compared with undergraduates, interpersonal distress has stronger associations with the mental health of offenders. This study further elaborates the interpersonal correlates of individual differences in personality and psychopathology across cultures and assessment contexts, and it also extends the literature examining interpersonal problems in forensic settings.

XPS Analysis of FexNiyPS3 vdW Materials Used in the Hydrogen Evolution Processes.

In response to the global demand for sustainable energy solutions, the quest for stable and cost-effective hydrogen production has garnered significant attention in recent decades. Here, the emergence of layered metal phosphorus trichalcogenides (MPX3, M: transition metal, X: chalcogen) materials and their two-dimensional counterparts with customizable composition and electronic structure holds great promise for such purposes. In the present study, we successfully synthesized large-scale and high-quality FePS3, NiPS3, and an alloyed counterpart, Fe0.5Ni0.5PS3. Subsequent systematic investigations were conducted to probe their respective electronic structures and assess their hydrogen evolution reaction (HER) properties. Remarkably, our results unveiled the successful modulation of the bandgap for FexNiyPS3, ultimately bestowing it with the most favorable HER performance for Fe0.5Ni0.5PS3 when compared to the other two samples. Furthermore, our exploration into the evolution of the X-ray photoelectron spectroscopy (XPS) spectra demonstrated that the charge conversions of metal cations play a pivotal role in the HER reactions. This critical insight further enriches our understanding of the fundamental mechanisms governing the performance of the prepared layered MPX3-based electrocatalysts, thus facilitating a comprehensive and detailed analysis of the pre- and post-HER reactions. This work not only sheds light on the intricate interplay between composition, electronic structure, and catalytic performance in the realm of novel electrocatalysts, but also contributes to the broader scientific community's pursuit of sustainable and efficient hydrogen production.

Historical and dispersal processes drive community assembly of multiple aquatic taxa in glacierized catchments in the Qinghai-Tibet plateau.

Understanding the relative role of dispersal dynamics and niche constraints is not only a core task in community ecology, but also becomes an important prerequisite for bioassessment. Despite the recent progress in our knowledge of community assembly in space and time, patterns and processes underlying biotic communities in alpine glacierized catchments remain mostly ignored. To fill this knowledge gap, we combined the recently proposed dispersal-niche continuum index (DNCI) with traditional constrained ordinations and idealized patterns of species distributions to unravel community assembly mechanisms of different key groups of primary producers and consumers (i.e., phytoplankton, epiphytic algae, zooplankton, macroinvertebrates, and fishes) in rivers in the Qinghai-Tibet Plateau, the World's Third Pole. We tested whether organismal groups with contrasting body sizes differed in their assembly processes, and discussed their applicability in bioassessment in alpine zones. We found that community structure of alpine river biotas was always predominantly explained in terms of dispersal dynamics and historical biogeography. These patterns are most likely the result of differences in species-specific functional attributes, the stochastic colonization-extinction dynamics driven by multi-year glacier disturbances and the repeated hydrodynamic separation among alpine catchments after the rising of the Qilian mountains. Additionally, we found that the strength of dispersal dynamics and niche constraints was partially mediated by organismal body sizes, with dispersal processes being more influential for microscopic primary producers. Finding that zooplankton and macroinvertebrate communities followed clumped species replacement structures (i.e., Clementsian gradients) supports the notion that environmental filtering also contributes to the structure of high-altitude animal communities in glacierized catchments. In terms of the applied fields, we argue that freshwater bioassessment in glacierized catchments can benefit from incorporating the metacommunity perspective and applying novel approaches to (i) detect the optimal spatial scale for species sorting and (ii) identify and eliminate the species that are sensitive to dispersal-related processes.

Impacts of Selenium-Chitosan Treatment on Color of "Red Globe" Grapes during Low-Temperature Storage.

Maintaining the vibrant color of fruit is a longstanding challenge in fruit and vegetable preservation. Chitosan and selenium, known for their protective and antioxidant properties, have been applied to preserve these produce. This study aimed to investigate the influence of selenium-chitosan treatment (comprising 25 mg L-1 selenium and 1.0% chitosan) on the color of "Red Globe" grapes and to analyze the relative expression of genes associated with anthocyanin synthesis enzymes (VvCHS, VvCHI, VvF3H, VvF3'H, VvF3'5'H, VvDFR, VvLDOX, VvUFGT, VvOMT, Vv5GT, and VvGST) using RT-qPCR. Our goal was to uncover the regulatory mechanisms governing grape color. Comparing various treatments, we observed that selenium-chitosan treatment had a significant effect in reducing decay, maintaining the soluble solids content of grape flesh, and preserving the vivid color of grape. This research indicated that selenium-chitosan treatment slowed down browning and prevented the reduction in total phenolic, flavonoids, and anthocyanin in the grape. Moreover, gene expression analysis revealed that selenium-chitosan treatment increased the expression of VvCHS, VvF3H, VvF'3'H, VvLDOX, and Vv5GT, while also stabilized the expression of VvCHI, VvF3'H, and VvDFR in grape skins. These findings shed light on the potential mechanism by which selenium-chitosan impacts grape color. This study established a theoretical foundation for investigating the molecular mechanisms behind selenium-chitosan's ability to slow down grape browning and provides a novel approach to enhancing fruit and vegetable preservation techniques.

Injectable hydrogel-based combination therapy for myocardial infarction: a systematic review and Meta-analysis of preclinical trials.

INTRODUCTION: This study evaluates the effectiveness of a combined regimen involving injectable hydrogels for the treatment of experimental myocardial infarction. PATIENT CONCERNS: Myocardial infarction is an acute illness that negatively affects quality of life and increases mortality rates. Experimental models of myocardial infarction can aid in disease research by allowing for the development of therapies that effectively manage disease progression and promote tissue repair. DIAGNOSIS: Experimental animal models of myocardial infarction were established using the ligation method on the anterior descending branch of the left coronary artery (LAD). INTERVENTIONS: The efficacy of intracardiac injection of hydrogels, combined with cells, drugs, cytokines, extracellular vesicles, or nucleic acid therapies, was evaluated to assess the functional and morphological improvements in the post-infarction heart achieved through the combined hydrogel regimen. OUTCOMES: A literature review was conducted using PubMed, Web of Science, Scopus, and Cochrane databases. A total of 83 papers, including studies on 1332 experimental animals (rats, mice, rabbits, sheep, and pigs), were included in the meta-analysis based on the inclusion and exclusion criteria. The overall effect size observed in the group receiving combined hydrogel therapy, compared to the group receiving hydrogel treatment alone, resulted in an ejection fraction (EF) improvement of 8.87% [95% confidence interval (CI): 7.53, 10.21] and a fractional shortening (FS) improvement of 6.31% [95% CI: 5.94, 6.67] in rat models, while in mice models, the improvements were 16.45% [95% CI: 11.29, 21.61] for EF and 5.68% [95% CI: 5.15, 6.22] for FS. The most significant improvements in EF (rats: MD = 9.63% [95% CI: 4.02, 15.23]; mice: MD = 23.93% [95% CI: 17.52, 30.84]) and FS (rats: MD = 8.55% [95% CI: 2.54, 14.56]; mice: MD = 5.68% [95% CI: 5.15, 6.22]) were observed when extracellular vesicle therapy was used. Although there have been significant results in large animal experiments, the number of studies conducted in this area is limited. CONCLUSION: The present study demonstrates that combining hydrogel with other therapies effectively improves heart function and morphology. Further preclinical research using large animal models is necessary for additional study and validation.

Sodium alginate/polyvinyl alcohol nanofibers loaded with Shikonin for diabetic wound healing: In vivo and in vitro evaluation.

Diabetic wounds are typically chronic wounds and the healing process is limited by problems such as high blood glucose levels, bacterial infections, and other issues that make wound healing difficult. Designing drug-loaded wound dressings is an effective way to promote diabetic wound healing. In this study, we developed an SA/PVA nanofiber (SPS) containing Shikonin (SK) for the treatment of diabetic wounds. The prepared nanofibers were uniform in diameter, had good hydrophilicity and high water vapor permeability, and effectively promoted gas exchange between the wound site and the outside world. The results of in vitro experiments showed that SPS was effective in antimicrobial, antioxidant, and biocompatible. In vivo tests showed that the wound healing rate of mice treated with SPS reached 85.5 %. Immunohistochemical staining results showed that SPS was involved in the diabetic wound healing process through the up-regulation of growth factors (CD31, HIF-1α) and the down-regulation of inflammatory factors (CD68). Western blotting experiments showed that SPS attenuated the inflammation through the inhibition of the IκBα/NF-κB signaling pathway. These results suggest that SPS is a promising candidate for future clinical application of chronic wound dressings.

Dopamine-grafted oxidized hyaluronic acid/gelatin/cordycepin nanofiber membranes modulate the TLR4/NF-kB signaling pathway to promote diabetic wound healing.

Due to impaired immune function, diabetic wounds are highly susceptible to the development of excessive inflammatory responses and prolonged recurrent bacterial infections that impede diabetic wound healing. Therefore, it is necessary to design and develop a wound dressing that controls bacterial infection and inhibits excessive inflammatory response. In this study, hyaluronic acid (HA) was modified using dopamine (DA). Subsequently, cordycepin (COR) was loaded into dopamine-modified hyaluronic acid (OHDA)/gelatin (GEL) nanofiber wound dressing by electrostatic spinning technique. The constructed COR/OHDA/GEL nanofiber membrane has good thermal stability, hydrophilicity, and air permeability. In vitro experiments showed that the obtained COR/OHDA/GEL nanofiber membranes had good antimicrobial efficacy (S. aureus: 95.60 ± 0.99 %, E. coli: 71.17 ± 6.87 %), antioxidant activity (>90 %), and biocompatibility. In vivo experiments showed that COR/OHDA/GEL nanofiber membranes could promote wound tissue remodeling, collagen deposition, and granulation tissue regeneration. Western blot experiments showed that COR/OHDA/GEL nanofibrous membranes could inhibit the excessive inflammatory response of wounds through the TLR4/NF-κB signaling pathway. Therefore, COR/OHDA/GEL nanofiber membranes could promote diabetic wound healing by modulating the inflammatory response. The results showed that the designed nanofiber wound dressing is expected to provide a new strategy for treating chronic wounds.

Effect of photobiomodulation on alleviating primary dysmenorrhea caused by PGF2α.

Photobiomodulation (PBM) has attracted widespread attention in suppressing various pain and inflammation. Primary dysmenorrhea (PD) primarily occurs in adolescents and adult females, and the limited effectiveness and side effects of conventional treatments have highlighted the urgent need to develop and identify new adjunct therapeutic strategies. In this work, the results of pain and PGs demonstrated that 850 nm, 630 nm, and 460 nm all exhibited pain inhibition, decreased PGF2α and upregulated PGE2, while 630 nm PBM has better effectiveness. Then to explore the underlying biological mechanisms of red light PBM on PD, we irradiated prostaglandin-F2α induced HUSM cells and found that low-level irradiance can restore intracellular calcium ion, ROS, ATP, and MMP levels to normal levels. And, red light enhanced cell viability and promoted cell proliferation for normal HUSM cells. Therefore, this study proposes that red light PBM may be a promising approach for the future clinical treatment of PD.

Hotspot Analysis and Frontier Exploration of Stem Cell Research in Intervertebral Disc Regeneration and Repair: A Bibliometric and Visualization Study.

BACKGROUND: Stem cells have shown tremendous potential and vast prospects in the research of intervertebral disc (IVD) regeneration and repair, attracting considerable attention in recent years. In this study, a bibliometric analysis and visualization techniques were employed to probe and analyze the hotspots and frontiers of stem cell research in IVD regeneration and repair, aiming to provide valuable references and insights for further investigations. METHODS: This study utilized the Science Citation Index Expanded from the Web of Science Core Collection database to retrieve and extract relevant literature records as research samples. Visual analysis tools such as VOSviewer 1.6.19, CiteSpace 6.2.R4, and bibliometric online analysis platforms were employed to construct scientific knowledge maps, providing a comprehensive and systematic exposition from various perspectives including collaboration networks, cocitation networks, and co-occurrence networks. RESULTS: A total of 1075 relevant studies have been published in 303 journals by 4181 authors from 1198 institutions across 54 countries/regions. Over the past 20 years, the field of research has witnessed a significant growth in annual publications and citations. China and the United States have emerged as the primary participants and contributors, with the AO Research Institute Davos, Zhejiang University, and Tokai University being the top 3 leading research institutions. The most productive and highly cited author is Sakai D, who is regarded as a key leader in this research field. The journals with the highest number of publications and citations are Spine and Biomaterials, which are considered to be high-quality and authoritative core journals in this field. The current research focuses primarily on the sources and selection of stem cells, optimization of transplantation strategies, mechanisms of IVD regeneration, and the combined application of stem cells and biomaterials. However, there are still some challenges that need to be addressed, including posttransplantation stability, assessment of regenerative effects, and translation into clinical applications. Future research will concentrate on the diversity of stem cell sources, the application of novel biomaterials, personalized treatments, and the development of gene editing technologies, among other cutting-edge directions. CONCLUSIONS: This study utilized bibliometric analysis and visualization techniques to unveil the hotspots and frontiers in the research on stem cells for IVD regeneration and repair. These research findings provide essential guidance and references for further experimental design and clinical applications. However, additional experiments and clinical studies are still needed to address the challenges and difficulties faced in the field of IVD regeneration and repair, thus offering novel strategies and approaches for the treatment of IVD diseases.

Polyvinyl alcohol/carboxymethyl chitosan-based hydrogels loaded with taxifolin liposomes promote diabetic wound healing by inhibiting inflammation and regulating autophagy.

With the improvement of modern living standards, the challenge of diabetic wound healing has significantly impacted the public health system. In this study, our objective was to enhance the bioactivity of taxifolin (TAX) by encapsulating it in liposomes using a thin film dispersion method. Additionally, polyvinyl alcohol/carboxymethyl chitosan-based hydrogels were prepared through repeated freeze-thawing. In vitro and in vivo experiments were conducted to investigate the properties of the hydrogel and its effectiveness in promoting wound healing in diabetic mice. The results of the experiments revealed that the encapsulation efficiency of taxifolin liposomes (TL) was 89.80 ± 4.10 %, with a drug loading capacity of 17.58 ± 2.04 %. Scanning electron microscopy analysis demonstrated that the prepared hydrogels possessed a porous structure, facilitating gas exchange and the absorption of wound exudates. Furthermore, the wound repair experiments in diabetic mice showed that the TL-loaded hydrogels (TL-Gels) could expedite wound healing by suppressing the inflammatory response and promoting the expression of autophagy-related proteins. Overall, this study highlights that TL-Gels effectively reduce wound healing time by modulating the inflammatory response and autophagy-related protein expression, thus offering promising prospects for the treatment of hard-to-heal wounds induced by diabetes.

The role of histone H1.2 in pancreatic cancer metastasis and chemoresistance.

AIMS: Pancreatic cancer (PC) is a highly metastatic malignant tumor of the digestive system. Drug resistance frequently occurs during cancer treatment process. This study aimed to explore the link between chemoresistance and tumor metastasis in PC and its possible molecular and cellular mechanisms. METHODS: A Metastasis and Chemoresistance Signature (MCS) scoring system was built and validated based on metastasis- and chemoresistance-related genes using gene expression data of PC, and the model was applied to single-cell RNA sequencing data. The influence of linker histone H1.2 (H1-2) on PC was explored through in vitro and in vivo experiments including proliferation, invasion, migration, drug sensitivity, rescue experiments and immunohistochemistry, emphasizing its regulation with c-MYC signaling pathway. RESULTS: A novel MCS scoring system accurately predicted PC patient survival and was linked to chemoresistance and epithelial-mesenchymal transition (EMT) in PC single-cell RNA sequencing data. H1-2 emerged as a significant prognostic factor, with its high expression indicating increased chemoresistance and EMT. This upregulation was mediated by c-MYC, which was also found to be highly expressed in PC tissues. CONCLUSION: The MCS scoring system offers insights into PC chemoresistance and metastasis potential. Targeting H1-2 could enhance therapeutic strategies and improve PC patient outcomes.

Effect of electroacupuncture on inflammatory response and immune cells in mice with chronic inflammatory pain. / ç”µé’ˆå¯¹æ ¢æ€§ç‚Žæ€§ç—›å°é¼ ç‚Žæ€§ååº”å’Œå ç–«ç»†èƒžçš„å½±å“.

OBJECTIVES: To observe the effects of electroacupuncture(EA) on local inflammatory mediators and macrophage polarization, and immune cells in the spleen of mice with chronic inflammatory pain induced by complete Freund's adjuvant (CFA) in the hind paw, so as to investigate the immunoinflammatory regulatory mechanisms of EA in relieving pain and swelling in mice with chronic inflammatory pain. METHODS: Thirty C57BL/6 mice were randomly divided into control, model, and EA groups, with 10 mice in each group. Chronic inflammatory pain model were established by subcutaneous injection of 20 µL CFA solution in the left hind paw for 7 consecutive days. After modeling, mice in the EA group received EA at bilateral "Zusanli"(ST36) for 20 min (2 Hz/100 Hz, 1 mA) once a day for 18 consecutive days. Mechanical pain threshold, heat pain thresholds, and paw thickness were measured before and after mode-ling, and after interventions. Western blot was used to detect the expression of tumor necrosis factor-alpha (TNF-α), interleukin (IL)-1ß, and NOD-like receptor protein 3 (NLRP3) in the paw tissue. Immunohistochemistry was used to detect the positive expression of M1-type macrophage marker inducible nitric oride synthase (iNOS) and M2-type marker CD206 in the paw, and flow cytometry was used to detect the proportion of F4/80+ CD11b+ macrophages, Ly6G+ CD11b+ neutrophils, and CD25+ Foxp3+ regulatory T cells (Treg) in the spleen. RESULTS: Compared with the control group, mechanical pain and heat pain thresholds were significantly reduced(P<0.000 1), while paw thickness, expressions of IL-1ß, TNF-α, and NLRP3 in the paw, and positive expression of M1 macrophage marker iNOS in the paw, the proportions of macrophages and neutrophils in the spleen were significantly increased (P<0.000 1, P<0.001) in the model group. Compared with the model group, mechanical pain threshold and heat pain thresholds, CD206 positive expression in the paw, and Treg cell proportion in spleen were significantly increased (P<0.01), while paw thickness, the expressions of IL-1ß, TNF-α and NLRP3 in the paw, as well as the positive expression of M1 macrophage marker iNOS in the paw, the proportions of macrophages and neutrophils in the spleen were significantly reduced (P<0.001, P<0.01, P<0.05)in mice of the EA group after intervention. CONCLUSIONS: EA may alleviate pain and swelling in mice with chronic inflammatory pain by regulating the numbers of macrophages, neutrophils, and Treg cells, as well as promoting M2 polarization of local macrophages and inhibiting the release of pro-inflammatory cytokines.

A dihydromyricetin-loaded phellinus igniarius polysaccharide/l-arginine modified chitosan-based hydrogel for promoting wound recovery in diabetic mice via JNK and TGF-ß/Smad signaling pathway.

The wound of diabetes has long-term excessive inflammation leading to wound fibrosis and scar formation. In the process of diabetic wound healing, good wound dressing is required for intervention. In this study, we designed a dihydromyricetin-loaded hydrogel (PCD) based on phellinus igniarius polysaccharide and l-arginine modified chitosan as an alternative material to promote diabetes wound healing. PCD had a uniform porous structure, good thermal stability, excellent mechanical properties, high water absorption, excellent antioxidant and anti-inflammatory activities and good biocompatibility and biodegradability. In addition, in the full-thickness skin trauma model of diabetes, PCD significantly inhibited the JNK signaling pathway to reduce inflammatory response, and significantly down-regulated the expression of TGF-ß1, Smad2, Smad3 and Smad4 to directly inhibit the TGF-ß/Smad signaling pathway to accelerate wound healing and slow down scar formation in diabetes mice. Therefore, PCD has a broad application prospect in promoting diabetes wound healing.