Catalpol attenuates ischemic stroke by promoting neurogenesis and angiogenesis via the SDF-1α/CXCR4 pathway.

BACKGROUND: Stroke is a leading cause of disability and death worldwide. Currently, there is a lack of clinically effective treatments for the brain damage following ischemic stroke. Catalpol is a bioactive compound derived from the traditional Chinese medicine Rehmannia glutinosa and shown to be protective in various neurological diseases. However, the potential roles of catalpol against ischemic stroke are still not completely clear. PURPOSE: This study aimed to further elucidate the protective effects of catalpol against ischemic stroke. METHODS: A rat permanent middle cerebral artery occlusion (pMCAO) and oxygen-glucose deprivation (OGD) model was established to assess the effect of catalpol in vivo and in vitro, respectively. Behavioral tests were used to examine the effects of catalpol on neurological function of ischemic rats. Immunostaining was performed to evaluate the proliferation, migration and differentiation of neural stem cells (NSCs) as well as the angiogenesis in each group. The protein level of related molecules was detected by western-blot. The effects of catalpol on cultured NSCs as well as brain microvascular endothelial cells (BMECs) subjected to OGD in vitro were also examined by similar methods. RESULTS: Catalpol attenuated the neurological deficits and improved neurological function of ischemic rats. It stimulated the proliferation of NSCs in the subventricular zone (SVZ), promoted their migration to the ischemic cortex and differentiation into neurons or glial cells. At the same time, catalpol increased the cerebral vessels density and the number of proliferating cerebrovascular endothelial cells in the infracted cortex of ischemic rats. The level of SDF-1α and CXCR4 in the ischemic cortex was found to be enhanced by catalpol treatment. Catalpol was also shown to promote the proliferation and migration of cultured NSCs as well as the proliferation of BMECs subjected to OGD insult in vitro. Interestingly, the impact of catalpol on cultured cells was inhibited by CXCR4 inhibitor AMD3100. Moreover, the culture medium of BMECs containing catalpol promoted the proliferation of NSCs, which was also suppressed by AMD3100. CONCLUSION: Our data demonstrate that catalpol exerts neuroprotective effects by promoting neurogenesis and angiogenesis via the SDF-1α/CXCR4 pathway, suggesting the therapeutic potential of catalpol in treating cerebral ischemia.

Gastrodin alleviates cisplatin nephrotoxicity by inhibiting ferroptosis via the SIRT1/FOXO3A/GPX4 signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Cisplatin (CP) results in acute kidney injury (AKI) and negatively affects patients' therapy and survival. The dried rhizome of Gastrodia elata Blume has been used to treat clinical kidney diseases. Gastrodin (GAS) is an active ingredient of the G. elata tuber. It is unknown whether GAS can alleviate CP-induced AKI. AIM OF THE STUDY: This study aimed to investigate whether GAS, an active ingredient of G. elata Blume, can alleviate CP-induced AKI and to explore its underlying mechanisms. MATERIALS AND METHODS: Experiments were conducted with a CP-induced AKI mouse model and an immortalized human renal tubular epithelial cell line (HK-2). Serum creatinine, Periodic acid-Schiff staining, tissue iron, glutathione, malondialdehyde, and 4-Hydroxynonenal were detected in serum and kidney samples to observe whether GAS inhibits CP-induced tubule ferroptosis. The drug target was verified by detecting the effects of GAS on sirtuin-1 (SIRT1) activity in vitro. Transcriptional regulation of glutathione peroxidase 4 (GPX4) by forkhead box O3A (FOXO3A) was verified by siRNA knockdown, overexpression, and chromatin immunoprecipitation. The effects of FOXO3A, SIRT1, and GAS on CP-induced ferroptosis were measured with propidium iodide, dihydroethidium, monobromobimane, and dipyrromethene boron difluoride staining in HK-2 cells. The relationship between GAS and the SIRT1/FOXO3A/GPX4 pathway was studied using Western blotting. RESULTS: GAS treatment inhibited CP-induced reactive oxygen species, lipid peroxidation, and tubule death in the cell and animal models. GAS activated SIRT1 in vitro. The SIRT1 inhibitor blocked the protective role of GAS in reducing lipid peroxidation in HK-2 cells. FOXO3A transcriptionally regulated GPX4 expression and inhibited CP-induced cell ferroptosis. Compared to CP-damaged mouse kidneys, GAS-treated mice demonstrated significantly increased SIRT1 and GPX4 expression levels, decreased CP-induced acetylation of FOXO3A, and inhibited lipid peroxidation and cell death. CONCLUSIONS: GAS alleviated CP-induced AKI by inhibiting ferroptosis via the SIRT1/FOXO3A/GPX4 signaling pathway. The results offer new insights into the development of new anti-AKI drugs from traditional Chinese medicine.

Tendon-to-bone healing after repairing full-thickness rotator cuff tear with a triple-loaded single-row method in young patients.

BACKGROUND: Arthroscopic repair is recommended for young patients with full-thickness rotator cuff tears (RCTs), but the healing rates have raised concerns. The Southern California Orthopedic Institute (SCOI) row method has been developed based on greater than 3 decades of experience with excellent clinical outcomes; however, studies with a focus on the younger patient population are limited in number. The current study assessed the short-term clinical outcome and the initial tendon-to-bone healing in a young cohort after repair of a full-thickness RCT using the SCOI row method. METHODS: A retrospective cohort study was performed. Patients < 55 years of age who had a full-thickness RCT and underwent an arthroscopic repair using the SCOI row method were reviewed. Clinical outcomes were assessed at baseline, and 3 and 6 months post-operatively. The visual analog scale (VAS), University of California at Los Angeles (UCLA) scale, and Constant-Murley score were completed to assess pain and function. Active range of motion was also examined, including abduction and flexion of the involved shoulder. A preoperative MRI was obtained to assess the condition of the torn tendon, while 3- and 6-month postoperative MRIs were obtained to assess tendon-to-bone healing. Repeated measurement ANOVA and chi-square tests were used as indicated. RESULTS: Eighty-nine patients (57 males and 32 females) with a mean age of 44.1 ± 8.6 years who met the criteria were included in the study. Compared with baseline, clinical outcomes were significantly improved 3 and 6 months postoperatively based on improvement in the VAS, UCLA score, and Constant-Murley score, as well as range of motion. Greater improvement was also noted at the 6-month postoperative assessment compared to the 3-month postoperative assessment. Three- and six-month postoperative MRIs demonstrated intact repairs in all shoulders and footprint regeneration, which supported satisfactory tendon-to-bone healing. The mean thickness of regeneration tissue was 7.35 ± 0.76 and 7.75 ± 0.79 mm as measured from the 3- and 6-month MRI (P = 0.002). The total satisfactory rate was 93.3 %. CONCLUSIONS: Arthroscopic primary rotator cuff repair of a full-thickness RCT using the SCOI row method in patients < 55 years of age yields favorable clinical outcomes and early footprint regeneration.

Less blood loss in supercapsular percutaneously assisted versus posterolateral total hip arthroplasty.

BACKGROUND: Although excellent clinical outcomes of supercapsular percutaneously assisted total hip arthroplasty (SuperPath) have been reported, the peri-operative blood loss has rarely been reported. The current study determined the blood loss during SuperPath and compared the blood loss with conventional posterolateral total hip arthroplasty (PLTH). METHODS: This retrospective study enrolled patients who underwent unilateral primary THA between January 2017 and December 2019. The demographic data, diagnoses, affected side, radiographic findings, hemoglobin concentration, hematocrit, operative time, transfusion requirements, and intra-operative blood loss were recorded. The peri-operative blood loss was calculated using the OSTHEO formula. Blood loss on the 1st, 3rd, and 5th post-operative days was calculated. Hidden blood loss (HBL) was determined by subtracting the intra-operative blood loss from the total blood loss. RESULTS: Two hundred sixty-three patients were included in the study, 85 of whom were in the SuperPath group and 178 in the posterolateral total hip arthroplasty (PLTH) group. Patient demographics, diagnoses, affected side, operative times, and pre-operative hemoglobin concentrations did not differ significantly between the two groups (all P > 0.05). Compared to the PLTH group, the SuperPath group had less blood loss, including intra-operative blood loss, 1st, 3rd, and 5th post-operative days blood loss, and HBL (all P < 0.05). Total blood loss and HBL was 790.07 ± 233.37 and 560.67 ± 195.54 mL for the SuperPath group, respectively, and 1141.26 ± 482.52 and 783.45 ± 379.24 mL for the PLTH group. PLTH led to a greater reduction in the post-operative hematocrit than SuperPath (P < 0.001). A much lower transfusion rate (P = 0.028) and transfusion volume (P = 0.019) was also noted in the SuperPath group. CONCLUSION: SuperPath resulted in less perioperative blood loss and a lower transfusion rate than conventional PLTH.

[Phylogenetic Processes and Key Driving Factors of Bacterial Communities in Jinze Reservoir].

To investigate the ecological mechanisms of the bacterial response to human disturbance in micro-polluted water ecosystems, we studied the relationship between the environmental factors and bacterial community development in the incoming water and various areas of a reservoir based on an ecological null model. The results showed that the phylogenetic clustering of bacterial communities was more dispersed than expected (the single-sample t-test of SES.MNTD has a 95% lower confidence limit of 9.79). Temperature is an important environmental factor affecting community phylogeny. The relative importance of stochastic and deterministic processes in the bacterial community succession of different samples showed seasonal characteristics. The bacterial community succession in spring, summer, and autumn samples was dominated by random and deterministic processes. NH4+-N is the main environmental factor affecting the relative importance of random and deterministic processes. When the concentration of NH4+-N is 0.06-0.40 mg ·L-1, the bacterial community succession is dominated by random processes; when the concentration is 0.40-0.80 mg ·L-1, it is dominated by both random and deterministic processes. Dispersal limitation (61.68%) and heterogeneous selection (26.65%) played important roles in bacterial community changes at different sampling points in the study area.

Biomechanical comparison between single-row with triple-loaded suture anchor and suture-bridge double-row rotator cuff repair.

BACKGROUND: Numerous biomechanical and clinical studies comparing different techniques for rotator cuff repair have been reported, yet universal consensus regarding the superior technique has not achieved. A medially-based single-row with triple-loaded suture anchor (also referred to as the Southern California Orthopedic Institute [SCOI] row) and a suture-bridge double-row (SB-DR) with Push-Locks have been shown to result in comparable improvement in treating rotator cuff tear, yet the biomechanical difference is unknown. The purpose of the current study was to determine whether a SCOI row repair had comparable initial biomechanical properties to a SB-DR repair. METHODS: Six matched pairs of fresh-frozen cadaveric shoulders with full-thickness supraspinatus tendon tears we created were included. Two different repairs were performed for each pair (SCOI row and SB-DR methods). Specimens were mounted on a material testing machine to undergo cyclic loading, which was cycled from 10 to 100 N at 1 Hz for 500 cycles. Construct gap formation was recorded at an interval of 50 cycles. Samples were then loaded to failure and modes of failure were recorded. Repeated-measures analysis of variance and pair-t test were used for statistical analyses. RESULTS: The construct gap formation did not differ between SCOI row and SB-DR repairs (P = 0.056). The last gap displacement was 1.93 ± 0.37 mm for SCOI row repair, and 1.49 ± 0.55 mm for SB-DR repair. The tensile load for 5 mm of elongation and ultimate failure were higher for SCOI row repair compared to SB-DR repair (P = 0.011 and 0.028, respectively). The ultimate failure load was 326.34 ± 11.52 N in the SCOI row group, and 299.82 ± 27.27 N in the SB-DR group. Rotator cuff repair with the SCOI row method failed primarily at the suture- tendon interface, whereas pullout of the lateral row anchors was the primary mechanism of failure for repair with the SB-DR method. CONCLUSION: Rotator cuff repair with the SCOI row method has superior biomechanical properties when compared with the SB-DR method. Therefore, SCOI row repair using a medially-based single-row technique with triple-loaded suture anchor is recommended to improve the initial strength in treating full-thickness rotator cuff tears.

Catalpol Enhances Neurogenesis And Inhibits Apoptosis Of New Neurons Via BDNF, But Not The BDNF/Trkb Pathway.

BACKGROUND: The role of catalpol in brain neurogenesis and newborn neuron survival has not been previously determined in permanent middle cerebral artery occlusion (pMCAO). METHODS: Fifty-four rats were divided into 6 groups: pMCAO (model, n=9); sham operation (NS, n=9); catalpol treatment (5 mg/kg and 10 mg/kg subgroups, n=9 each); K252a (n=9); and K252a+catalpol 5 mg/kg (n=9) with stroke. The effects of catalpol on behavior, neurogenesis surrounding the infarction ipsilateral to pMCAO, and the expression of brain-derived neurotrophic factor (BDNF) and its receptor (TrkB) were evaluated. Vehicle or, K252a (i.p.), an inhibitor of TrkB phosphorylase. RESULTS: Repeated administration of catalpol reduced neurological deficits and significantly improved neurogenesis. Catalpol increased the number of newborn immature neurons, as determined by BrdU+-Nestin+ and BrdU+-Tuj-1+ staining, and downregulated cleaved caspase 3 in Tuj-1+ cells at day 7 following stroke. Moreover, catalpol increased the protein expression of Tuj-1, MAP2, and the Bcl-2/Bax ratio, as determined using Western blot. Catalpol also significantly increased brain levels of BDNF, but not TrkB, resulting in enhanced survival of newborn neurons via inhibition of apoptosis. CONCLUSION: Catalpol may contribute to neurogenesis in infarcted brain regions and help promote the survival of newborn neurons by activating BDNF, but not BDNF/TrkB signaling.

[Spatio-temporal Distribution Characteristics of the Water Quality in the Jinze Reservoir and Its Inflow].

Jinze Reservoir is the main drinking water source for southwest Shanghai. The water quality in the upstream Taipu River and reservoir have an important impact on the performance of the reservoir and the quality of the water supply. Conventional water parameters were analyzed using principal component analysis (PCA) to evaluate seasonal variations in water quality in the upper reaches of Jinze Reservoir. The parallel factor (PARAFAC) was also used to analyze water-soluble dissolved organic matter (FDOM) in the upstream waters and reservoir area. Furthermore, the relationships between water fluorescence intensity and conventional water quality indicators were analyzed using correlation analysis. The results show that water quality in the upper reaches of Jinze Reservoir is worst in the winter, and water quality gradually deteriorates in the outer sections of the reservoir due to external pollution inputs. Ecological purification within the reservoir area functions to improve water quality. The water body FDOM content is mainly composed of proteinoids and humus. Protein-like substances are the main components of this material, and each component exhibits clear spatial and temporal distribution characteristics. External pollution is the main factor affecting the total fluorescence intensity of the FDOM outside of the reservoir. In the reservoir, the ecological environment affects the total fluorescence intensity of FDOM. The total fluorescence intensity of FDOM showed an increasing downstream spatial trend, which was significantly correlated with NH4+-N, petroleum, TOC, chloride, and sulfate content in the water. By detecting the total fluorescence intensity of FDOM, the rapid analysis of water quality can be achieved to inform early warning.

[Protective effect of catalpolon destruction of tight junctions of high glucose induced BMECs].

This paper aimed to observe the protective effect of catalpol on the high glucose induced destruction of tight junctions of rat primary brain microvascular endothelial cells (BMECs). Catalpol co-administrated with high glucose increased BMECs survival, decreased its ET-1 secretion, and improved transmembrane electrical resistance in a time-dependent manner. Furthermore, transmission electron microscopy was used to observe catalpol's protective effect on tight junction. Fluorescence staining displayed that catalpol reversed the rearrangement of the cytoskeleton protein F-actin and up-regulated the tight junction proteins claudin-5 and ZO-1, which were further demonstrated by the mRNA expression levels of claudin-5, occludin, ZO-1, ZO-2, ZO-3, α-actintin, vinculin and cateinins. This study indicated that catalpol reverses the disaggregation of cytoskeleton actin in BMECs and up-regulates the expression of tight junction proteins, such as claudin-5, occludin, and ZO-1, and finally alleviates the increase in high glucose-induced BMECs injury.

[Effects of Schisandrae Chinensis Fructus induced CYPs and Nrf2 activation on acute liver injury induced by acetaminophen].

Schisandra chinensis is a commonly used hepatoprotective medicine in clinic. Previous studies have showed that Schisandrae Chinensis Fructus has dual effects on the activity of CYPs. Short-term administration of Schisandrae Chinensis Fructus may inhibit CYP450s activity, while long-term administration may up-regulate CYP activity. High CYP450s activity level may increase the frequency of reactive metabolites-induced liver injury. It remains unclear how long-term administration of Schisandrae Chinensis Fructus may affect acetaminophen-induced acute hepatotoxicity. After oral administration of Schisandrae Chinensis Fructus extract (0.5-2.0 g·kg⁻¹) for 21 d, the activity of CYPs, Nrf2, HO-1, GST expressions, SOD and GST activity as well as glutathione level of SD rats were up-regulated. Besides, Schisandrae Chinensis Fructus extract ameliorated APAP (500 mg·kg⁻¹)-induced acute hepatotoxicity in a dose-dependent manner, as evidenced by decrease in ALT, AST, and MDA level and increase in GSH level (P<0.05). What's more, the liver histopathology was alleviated, and cleaved caspase-3 expression was decreased. Besides, the increase of N-acetyl-p-benzoquinoneimine-GSH (reactive metabolite of acetaminophen) formation was observed in Schisandrae Chinensis Fructus extract groups. In conclusion, the present study indicated that the effects of Schisandrae Chinensis Fructuson acetaminophen-induced hepatotoxicity may rely on the Nrf2 signal pathway activation, and less depends on the increase in CYP450s activity.

Catalpol increases brain angiogenesis and up-regulates VEGF and EPO in the rat after permanent middle cerebral artery occlusion.

To investigate the role and mechanism of catalpol in brain angiogenesis in a rat model of stroke, the effect of catalpol (5 mg/kg; i.p) or vehicle administered 24 hours after permanent middle cerebral artery occlusion (pMCAO) on behavior, angiogenesis, ultra-structural integrity of brain capillary endothelial cells, and expression of EPO and VEGF were assessed. Repeated treatments with Catalpol reduced neurological deficits and significantly improved angiogenesis, while significantly increasing brain levels of EPO and VEGF without worsening BBB edema. These results suggested that catalpol might contribute to infarcted-brain angiogenesis and ameliorate the edema of brain capillary endothelial cells (BCECs) by upregulating VEGF and EPO coordinately.

[Recent advances of Drynaria fortunei].

Drynaria fortunei (Kunze) is a common medicine in department of orthopaedics and traumaology, more researches about it recently, including basic theory, pharmaco and clinical study.

[Effects of Rehmannia root decoction serum on cell proliferation and EPO expression in cultured human umbilical vein endothelial cells].

OBJECTIVE: To explore the efficacy of the rehmannia root decoction containing serum in enhencing the proliferation of HUVECs-1 and EPO expression and to give libratory evidence for the tonifying blood and kidney therapy with rehmannia root. METHOD: Twenty-four male Sprague-Dawley rats were randomly devided into 4 group and administrered by gastrogavage rehmannia root decoction of 3, 6, 10 g x kg(-1) once a day for 1 weeks. Using serum pharmacologic method, the proliferation of HUVECs-1 cell was determined by MTT chromatometry at 48 h points by co-culturing with medicated serum containing different concentration of rehmannia root decoction. The expression of EPO on HUVECs-1 were observed by immunity cytochemistry and Western blot. NS serum was taken as control. RESULT: After the HUVECs-1 cultivating with medicated serum for 48 h, compared with NS serum, 20% serum containing rehmannia root (6 g x kg(-1)) could obviously increase proliferation of HUVEC-1 (P < 0.05) and increase the level of the expression of EPO on HUVECs-1 (P < 0.05). CONCLUSION: Rehmannia root extract has good actions of proliferation of HUVECs-1 and increase EPO expression, which is the mechanisms of nourishing yin and blood and tonifying essence of rehmannia root.

[Study of catalpol promoting axonal growth for cultured cortical neurons from rats].

OBJECTIVE: To explore the effects of different concentration of catalpol on the cell survival and axonal growth of cortical neurons cultured in vitro from 24 h newly born rat. METHOD: Primary cultured cortical neurons from 24 h newly born rat were dissociated and cultured. The different concentration of catalpol and 1 mg mL(-1) citicoline were added to the culture plates for 48 h, and the final of catalpol concentration were 0.25, 0.5, 1, 2.5, 5 mg mL(-1), respectively. The cortical neuron was identified by NF-200 antigen and its survival activity detected by MTT assay. The axonal growth of cultured cortical neuron were observed by inverted microscopy with micrometer. RESULT: Immunocytochemistry demonstrated more than 95% of the primary cultured cortical neurons were positive for NF-200 antigen, which indicated the cultured cells were neurons. Neurons survived growing on the concentration of 0.25, 0.5, 1, 2.5, 5 mg mL(-1). Compared with blank and 1 mg mL(-1) citicoline group,neurons survival rates were not statistical significant difference. However, it demonstrated that catalpol significantly promoted axonal growth from 1-5 mg mL(-1) (P <0.05). Interestedly, compared with the dose of 2.5 mg mL(-1), axonal growth was shorter at the dose of 5 mg mL(-1), and 2.5 mg mL(-1) catalpol showed the strongest promotion effect. CONCLUSION: The catalpol can enhance cortical neuron axonal growth, but not promote cortical neuron survival.