Caspase independent cleavages of TDP-43 generates 35kD fragment that cause apoptosis of breast cancer cells.

Transactive response DNA-binding protein 43kD (TDP-43) is a major component of tau-negative and ubiquitin-positive inclusions that characterize ALS (amyotrophic lateral sclerosis) and FTLD (frontotemporal lobar degeneration). Due to its central role in neurodegenerative disease pathogenesis, most research recently has focused on its role associated with neurodegeneration disease, research on neuron and glial cell showed that pathological TDP-43 is associated with cell apoptosis which lead to loss of functional neurons and glial cells. However, little is known about its role on cancer cells, here we report a 35kD fragment of TDP-43 also plays a key role in apoptosis of breast cancer cells, and may be served as a potential therapeutic target to cure cancer.

Gastrodin facilitates recovery of neurological function of MCAO rats through upregulating miR-20a-5p/XIAP pathway via exosome.

Cerebral infarction (CI) is characterised by high morbidity, mortality, and disability rates. Recently, Chinese medicine has been widely used and has gained satisfactory results in the treatment of CI. Our previous study showed that gastrodin could facilitate the recovery of neurological function in middle cerebral artery occlusion (MCAO) rats. This study explores this mechanism. SD rats were separated into control, sham, model, and gastrodin groups. After MCAO surgery, the gastrodin group was administered gastrodin (100 mg/kg), and after 1/3/7 days, the ischaemic hemisphere and serum was collected, and then we extracted the circulating exosomes from the serum. We then tested the levels of XIAP (x-linked inhibitor of apoptosis protein), IAP binding proteins (SMAC, HtrA2, ARTs), and miR-20a-5p (a gastrodin potential effect target) in the brain tissues, circulating exosomes, and serum using various methods. Our results showed that circulating exosomes can penetrate the blood-brain barrier (BBB) and that gastrodin can upregulate the amount of miR-20a-5p in circulating exosomes. The circulating exosomes penetrate the BBB and upregulate the expression of XIAP in the ischaemic hemisphere. Gastrodin can also decrease the amount of IAP binding proteins (SMAC, HtrA2, ARTs). Gastrodin can increase the amount of miR-20a-5p in circulating exosomes, which penetrates the BBB and upregulates XIAP expression in the ischaemic hemisphere. By inhibiting apoptosis of neurones, it can facilitate the recovery of neurological function in MCAO rats.

Effect of TMAO on the incidence and prognosis of cerebral infarction: a systematic review and meta-analysis.

Objective: This study aimed to evaluate the effect of trimethylamine oxide (TMAO) on the incidence and prognosis of cerebral infarction. Methods: We searched PubMed, Embase, and Cochrane databases for all clinical studies on the association of TMAO with cerebral infarction incidence and prognosis from inception to April 2023. A systematic review and meta-analysis were conducted using the meta-analysis of observational studies in epidemiology (MOOSE) declaration list. The Newcastle-Ottawa Scale (NOS) was used to assess the quality of the study. This study protocol was registered on the PROSPERO database with the ID: CRD42023459661. The extracted data included the OR value of the effect of TMAO on the incidence and prognosis of cerebral infarction, the HR value between TMAO and underlying diseases, the RR value, 95% confidence intervals, and the AUC value of TMAO in the prediction model of cerebral infarction. Results: Fifteen studies including 40,061 patients were included. All the patients were from China or Germany. The TMAO level was significantly correlated with the Modified Rankin Score (mRS) 3 months after the onset of cerebral infarction (OR, 1.581; 95% CI, 1.259-1.987; p < 0.01). The TMAO level was significantly correlated with the rate of first-time incidence and recurrence of cerebral infarction (OR, 1.208; 95% CI, 1.085-1.344; p < 0.01 and HR, 1.167; 95% CI, 1.076-1.265; p < 0.01, respectively). The TMAO level was also highly correlated with disease severity at onset (National Institutes of Health Stroke Scale, NIHSS >5) (OR, 5.194; 95% CI, 1.206-22.363; p < 0.05), but had no significant correlation with mortality after cerebral infarction (p > 0.05). Correlation analysis of TMAO with underlying diseases in the population indicated that TMAO had a significant correlation with histories of hypertension, diabetes mellitus, coronary artery disease, and cerebral infarction (p < 0.05), but not with hyperlipidemia (p > 0.05). Six risk prediction models of TMAO for cerebral infarction reported in four studies were systematically evaluated; five of them had good predictive value (AUC ≥ 0.7). Conclusion: TMAO is an independent risk factor affecting the onset, prognosis, and severity of cerebral infarction.

Bioinformatics Analysis of Gene Expression Profiles of Sex Differences in Ischemic Stroke.

Ischemic stroke (IS) is a complex disease with sex differences in epidemiology, presentations, and outcomes. However, the sex-specific mechanism underlying IS remains unclear. The purpose of this study was to identify key genes contributing to biological differences between sexes. First, we downloaded the gene expression data of GSE22255 from Gene Expression Omnibus (GEO). Differentially expressed genes (DEGs) were identified using R software and related packages. Second, DEGs were separately analyzed by Gene Ontology enrichment and pathways analyses. Third, protein-protein interaction (PPI) network was constructed to further investigate the interactions of DEGs. A total of 123 DEGs were identified between sexes, including 8 upregulated and 115 downregulated genes. In the PPI network, ten key genes were identified, including IL1α, IL1ß, IL6, IL8, CXCL1, CXCL2, CXCL20, CCL4, ICAM1, and PTGS2. Functional enrichment analysis revealed that these genes were mainly enriched in biological processes of immune response and apoptotic process, also in pathways of TNF and NOD-like receptor signaling. In conclusion, the above ten genes may have a protective effect on IS females through their direct or indirect involvement in biological processes of immune response and apoptotic process, as well as in TNF and NOD-like receptor signaling pathways. The results of this study may help to gain new insights into the sex-specific mechanisms underlying IS females and may suggest potential therapeutic targets for disease treatment.

Gastrodin improves the neurological score in MCAO rats by inhibiting inflammation and apoptosis, promoting revascularization.

Gastrodin (GAS) is an active constituent of Chinese herbal medicine tianma (Gastrodia elata), which is commonly used to extinguish wind (TCM term). Tianma is also widely used to treat various neurological diseases such as stroke, dizziness, epilepsy, etc. Its clinical effect is quite satisfactory. However, the underlying mechanism has not been fully explored. In the present study, we choose a permanent cerebral occlusion model, MCAO, and used multiple methods to investigate the medicine. Our results show a significant improvement in neurological score after 3 days of GAS treatment. In addition, neurons in the hippocampus were rescued within after 7 days GAS treatment. Then we explore the drug's mechanism in the acute phase of stroke. CRP and IL-1ß are common inflammatory factors. Elisa showed GAS can reduce these inflammatory factors in serum in the acute phase of stroke. What's more, GAS can up-regulate the expression of Bcl-2 and down-regulate the expression of BAX in the ischemic hemisphere, and the same result is observed in the protein level. The expression of Caspase-3 is also suppressed, indicating GAS has ability to inhibit apoptosis during the acute phase of stroke. On the other hand, GAS can up-regulate the expression of VEGF, thusly promoting micro-vacsular regeneration. In conclusion, our results demonstrate that GAS can alleviate the symptoms of stroke through various mechanisms. GAS might also serve as a potential candidate to treat acute cerebral infarction.

The Study of Dynamic Characteristic of Acupoints Based on the Primary Dysmenorrhea Patients with the Tenderness Reflection on Diji (SP 8).

In TCM theory, acupoint is not a fixed point but a portal with dynamic characteristics where the channel qi enters and flows out. The dynamic characteristics have been verified primarily by detecting the tenderness reaction on Diji (SP 8) in primary dysmenorrhea patients. In this study, finger pressing and algometer were applied in Diji (SP 8) area of participants in menstrual period and nonmenstrual period, respectively, to detect the tenderness occurrence rate, the VAS score of the tenderest point, the tenderness threshold of the tenderest point, and the location of the tenderest point. The result suggests that the acupoint may not be a fixed location but a point in a dynamic state within a certain range in time and space varying with different physiological and pathological status.

Staurosporine induced apoptosis rapidly downregulates TDP- 43 in glioma cells.

TDP-43 is a ubiquitously expressed DNA/RNA binding protein that has recently attracted attention for its involvement in neurodegenerative diseases. While TDP-43 has been found to participate in various important cellular activities including stress and apoptosis, little is known about its role in cancer cells. Here we report that staurosporine (STS) induced apoptosis in U87 glioma cells is associated with rapid downregulation of TDP-43 at both mRNA and protein levels. The latter is dependent on activation of caspase 3. More importantly, we have shown that knockdown of TDP-43 by specific siRNA dramatically enhanced cytotoxicity of STS. These results suggest that normal level of TDP-43 may be protective for cancer cells under apoptotic insult.

Appraisal of the Deqi Concept among Contemporary Chinese Acupuncturists.

Deqi, an important component of the traditional theory of acupuncture and moxibustion, is the key factor in determining clinical therapeutic effect of acupuncture. In this paper, based on the digging up, arrangement, and in-depth analysis of the famous contemporary Chinese acupuncturists' perspectives of deqi, the authors summarize the concept and manifestation, as well as the properties of deqi, and correlativity of deqi with acupuncture manipulation through reviewing modern clinical research. Proposals for more scientific and standardized acupuncture research are introduced to reexamine and restore the implication of deqi in combination with the clinical practice.