Role of intracranial bone marrow mesenchymal stem cells in stroke recovery: A focus on post-stroke inflammation and mitochondrial transfer.

Stem cell therapy has become a hot research topic in the medical field in recent years, with enormous potential for treating a variety of diseases. In particular, bone marrow mesenchymal stem cells (BMSCs) have wide-ranging applications in the treatment of ischemic stroke, autoimmune diseases, tissue repair, and difficult-to-treat diseases. BMSCs can differentiate into multiple cell types and exhibit strong immunomodulatory properties. Although BMSCs can regulate the inflammatory response activated after stroke, the mechanism by which BMSCs regulate inflammation remains unclear and requires further study. Recently, stem cell therapy has emerged as a potentially effective approach for enhancing the recovery process following an ischemic stroke. For example, by regulating post-stroke inflammation and by transferring mitochondria to exert therapeutic effects. Therefore, this article reviews the therapeutic effects of intracranial BMSCs in regulating post-stroke inflammation and mitochondrial transfer in the treatment of stroke, providing a basis for further research.

Mitochondrial Transplantation and Immune Response of Human Bone Marrow Mesenchymal Stem Cells for the Therapeutic of Ischemic Stroke.

Ischemic stroke is the leading cause of death and disability worldwide, with increasing incidence and mortality, imposing a significant social and economic burden on patients and their families. However, cerebral vascular occlusion leads to acute loss of neurons and destruction of synaptic structures. The limited treatment options cannot adequately address intra-neuronal mitochondrial dysfunction due to stroke. Therefore, stem cell-derived mitochondria transplantation plays an important role in neuronal protection and recovery after stroke, when combined with the intracranial and extracranial immunoregulatory effects of stem cell therapy, revealing the mechanism of transferred mitochondria in stem cells in protecting neurological function among chronic-phase ischemic stroke by affecting the endogenous apoptotic pathway of neuronal cells. This research elaborated on the mitochondrial dysfunction in neurons after ischemic stroke, followed by human bone marrow mesenchymal stem cells (hBMSC) rescued damaged neurons by mitochondrial transfer through tunneling nanotubes (TNTs), and the immunomodulatory effect of the preferential transfer of stem cells to the spleen when transplanted into the body.which created an immune environment for nerve repair, as well as improved neurological recovery after the chronic phase of stroke. This review is expected to provide a novel idea for applying intracranial stem cell transplantation in chronic-phase ischemic stroke treatment.

Effects of exogenous melatonin on growth and physiological characteristics of Agropyron mongolicum seedlings under drought stress.

To clarify the alleviation effect of exogenous melatonin (MT) on Agropyron mongolicum under drought stress, we examined the response of A. mongolicum 'Yanchi' seedlings to simulated drought stress with polyethylene glycol 6000 (PEG-6000), by investigating the effects of exogenous addition of different concentrations (0, 1, 10, 50, 100, 150 and 200 mg·L-1) of MT on seedlings growth and physiological characteristics under drought stress. The results showed that drought stress significantly inhibited the growth of A. mongolicum seedlings, and that exogenous addition of different concentrations of MT could alleviate the growth inhibition caused by drought stress, with the strongest mitigation effect observed at MT concentration of 100 mg·L-1. Compared with the drought stress treatment alone, exogenous addition of 100 mg·L-1 MT under drought stress increased plant height, aboveground dry weight, and leaf relative water content by 58.2%, 121.2% and 48.1%. The contents of chlorophyll a, chlorophyll b, carotenoids increased by 48.7%, 80.8% and 38.3%, superoxide dismutase, peroxidase and root activity increased by 12.6%, 33.9% and 39.1%, and the contents of ascorbic acid and glutathione increased by 19.5% and 18.3%, respectively. The contents of proline, soluble sugar and soluble protein were increased by 16.2%, 32.6% and 14.3%, while that of malondialdehyde, hydrogen peroxide and superoxide anion radical were decreased by 45.8%, 65.8% and 30.8%, respectively. In summary, exogenous addition of 100 mg·L-1 MT could improve drought tolerance of A. mongolicum seedlings by promoting growth, enhancing antioxidant capacity, increasing the content of osmoregulation substances, inhibiting the excessive production of reactive oxygen, and reducing membrane peroxide level.

Genome-wide investigation and expression analysis of OSCA gene family in response to abiotic stress in alfalfa.

Alfalfa is an excellent leguminous forage crop that is widely cultivated worldwide, but its yield and quality are often affected by drought and soil salinization. Hyperosmolality-gated calcium-permeable channel (OSCA) proteins are hyperosmotic calcium ion (Ca2+) receptors that play an essential role in regulating plant growth, development, and abiotic stress responses. However, no systematic analysis of the OSCA gene family has been conducted in alfalfa. In this study, a total of 14 OSCA genes were identified from the alfalfa genome and classified into three groups based on their sequence composition and phylogenetic relationships. Gene structure, conserved motifs and functional domain prediction showed that all MsOSCA genes had the same functional domain DUF221. Cis-acting element analysis showed that MsOSCA genes had many cis-regulatory elements in response to abiotic or biotic stresses and hormones. Tissue expression pattern analysis demonstrated that the MsOSCA genes had tissue-specific expression; for example, MsOSCA12 was only expressed in roots and leaves but not in stem and petiole tissues. Furthermore, RT-qPCR results indicated that the expression of MsOSCA genes was induced by abiotic stress (drought and salt) and hormones (JA, SA, and ABA). In particular, the expression levels of MsOSCA3, MsOSCA5, MsOSCA12 and MsOSCA13 were significantly increased under drought and salt stress, and MsOSCA7, MsOSCA10, MsOSCA12 and MsOSCA13 genes exhibited significant upregulation under plant hormone treatments, indicating that these genes play a positive role in drought, salt and hormone responses. Subcellular localization results showed that the MsOSCA3 protein was localized on the plasma membrane. This study provides a basis for understanding the biological information and further functional analysis of the MsOSCA gene family and provides candidate genes for stress resistance breeding in alfalfa.

Effects of long-term regular oral aspirin combined with atorvastatin to prevent ischemic stroke on human gut microbiota.

PURPOSE: Every year, there is a large number of people take aspirin and atorvastatin to prevent ischemic stroke, but the effect of these drugs on gut microbiota remains unknown. We aimed to examine the effects of long-term regular oral aspirin with atorvastatin to prevent ischemic stroke on human gut microbiota. METHODS: A cross-sectional study of 20 participants with the drugs over one year and the other 20 gender- and age-matching participants without medication were recruited from the Affiliated Hospital of Guizhou Medical University. The medication habits and dietary information were obtained using a questionnaire. Fecal samples collected from all participants were subjected to 16S rRNA sequencing of the microbiome. The datasets were analyzed using bioinformatics approaches. RESULTS: The Alpha diversity showed that compared with controls, medication participants had lower ACE and Chao1 index, while no difference in the Shannon index and Simpson index. The Beta diversity analysis revealed significant shifts in the taxonomic compositions of the two groups. Linear discriminant analysis effect size (LEfSe) analysis combined with receiver operating characteristic (ROC) curves revealed the marker bacteria associated with taking medication were g_Parabacteroides（AUC = 0.855）, g_Bifidobacterium（AUC = 0.815）, s_Bifidobacterium_longum_subsp（AUC = 0.8075）, and with no taking medication was g_Prevotella_9（AUC = 0.76）. CONCLUSIONS: Our findings indicated that long-term regular oral aspirin and atorvastatin modulate the human gut microbiota. Taking these drugs may affect the preventive effect of ischemic stroke by changing the abundance of specific gut microbiota.

Transcriptome analysis and physiological changes in the leaves of two Bromus inermis L. genotypes in response to salt stress.

Soil salinity is a major factor threatening the production of crops around the world. Smooth bromegrass (Bromus inermis L.) is a high-quality grass in northern and northwestern China. Currently, selecting and utilizing salt-tolerant genotypes is an important way to mitigate the detrimental effects of salinity on crop productivity. In our research, salt-tolerant and salt-sensitive varieties were selected from 57 accessions based on a comprehensive evaluation of 22 relevant indexes, and their salt-tolerance physiological and molecular mechanisms were further analyzed. Results showed significant differences in salt tolerance between 57 genotypes, with Q25 and Q46 considered to be the most salt-tolerant and salt-sensitive accessions, respectively, compared to other varieties. Under saline conditions, the salt-tolerant genotype Q25 not only maintained significantly higher photosynthetic performance, leaf relative water content (RWC), and proline content but also exhibited obviously lower relative conductivity and malondialdehyde (MDA) content than the salt-sensitive Q46 (p < 0.05). The transcriptome sequencing indicated 15,128 differentially expressed genes (DEGs) in Q46, of which 7,885 were upregulated and 7,243 downregulated, and 12,658 DEGs in Q25, of which 6,059 were upregulated and 6,599 downregulated. The Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that the salt response differences between Q25 and Q46 were attributed to the variable expression of genes associated with plant hormone signal transduction and MAPK signaling pathways. Furthermore, a large number of candidate genes, related to salt tolerance, were detected, which involved transcription factors (zinc finger proteins) and accumulation of compatible osmolytes (glutathione S-transferases and pyrroline-5-carboxylate reductases), etc. This study offers an important view of the physiological and molecular regulatory mechanisms of salt tolerance in two smooth bromegrass genotypes and lays the foundation for further identification of key genes linked to salt tolerance.

Exogenous melatonin ameliorates drought stress in Agropyron mongolicum by regulating flavonoid biosynthesis and carbohydrate metabolism.

Drought is one of the most common abiotic stressors in plants. Melatonin (MT) is a high-efficiency and low-toxicity growth regulator that plays an important role in plant responses to drought stress. As a wild relative of wheat, Agropyron mongolicum has become an important species for the improvement of degraded grasslands and the replanting of sandy grasslands. However, the physiological and molecular mechanisms by which exogenous MT regulates drought stress in A. mongolicum remain unclear. To assess the effectiveness of MT intervention (100 mg·L-1), polyethylene glycol 6000 was used to simulate drought stress, and its ameliorating effects on drought stress in A. mongolicum seedlings were investigated through physiology, transcriptomics, and metabolomics. Physiological analysis indicated that MT treatment increased the relative water content and chlorophyll content and decreased the relative conductivity of A. mongolicum seedlings. Additionally, MT decreased malondialdehyde (MDA) and reactive oxygen species (ROS) accumulation by enhancing antioxidant enzyme activities. The transcriptome and metabolite profiling analysis of A. mongolicum seedlings treated with and without MT under drought stress identified the presence of 13,466 differentially expressed genes (DEGs) and 271 differentially expressed metabolites (DEMs). The integrated analysis of transcriptomics and metabolomics showed that DEGs and DEMs participated in diverse biological processes, such as flavonoid biosynthesis and carbohydrate metabolism. Moreover, MT may be involved in regulating the correlation of DEGs and DEMs in flavonoid biosynthesis and carbohydrate metabolism during drought stress. In summary, this study revealed the physiological and molecular regulatory mechanisms of exogenous MT in alleviating drought stress in A. mongolicum seedlings, and it provides a reference for the development and utilization of MT and the genetic improvement of drought tolerance in plants from arid habitats.

[Effect of cervical paravertebral block combined with acupuncture intervention on cervicogenic headache].

OBJECTIVE: To observe the therapeutic effect of cervical paravertebral block plus acupuncture treatment for cervicogenic headache. METHODS: Sixty cases of cervicogenic headache were randomly and equally divided into cervical paravertebral block (control) group and acupuncture plus cervical paravertebral block (acupuncture) group. Paravertebral block was performed by injection of 5 mL of 0.3% lidocaine solution containing triamcinolone (10 mg) into the 2nd cervical paravertebral tissue from the cross point between the posterior border of the sternomastoid muscle and the angle of jaw, once every week for three weeks. Manual acupuncture stimulation was applied to Baihui (GV 20), unilateral Fengchi (GB 20) and Jiaosun (SJ 20), once daily for 3 weeks. The patients' headache severity was assessed by visual analogue scale (VAS) and their cervical vertebral activity assessed by range of motion (ROM) before and after the treatment. RESULTS: Compared with pre-treatment in the same one group, the scores of both VAS and ROM at time points of one, two and three weeks after the treatment were significantly decreased in the control and acupuncture groups (P < 0.05), suggesting a marked improvement of both headache and cervical motion after the treatment. Comparison between the two groups showed that the VAS and ROM scores of the acupuncture group were evidently lower than those of the control group at each time point after the treatment (P < 0.05), displaying a better therapeutic effect of acupuncture plus paravertebral block for cervicogenic headache. CONCLUSION: Acupuncture combined with cervical paravertebral block is effective in relieving cervicogenic headache and improving cervical vertebral activity in cervicogenic headache patients, and can strengthen the therapeutic effect of simple paravertebral block.