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.

Catalpol rescues LPS-induced cognitive impairment via inhibition of NF-Κb-regulated neuroinflammation and up-regulation of TrkB-mediated BDNF secretion in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Septic-associated encephalopathy (SAE) is a key manifestation of sepsis. Nevertheless, specific treatment for SAE is still lacking. Catalpol is an active component derived from Rehmanniae Radix, and has been demonstrated to be a potential neuroprotective agent. However, its effect on SAE still needs to be fully explored. AIM: To address the benefits of catalpol on post-sepsis cognitive deterioration and related mechanisms. MATERIALS AND METHODS: Novel object recognition test, temporal order task, histopathology, and immunochemistry were applied to address the benefits of catalpol on LPS-triggered post-sepsis cognitive decline in mice. Xuebijing injection (10 ml/kg) has been utilized as a positive control in the above animal studies. After treatment, the catalpol content in the hippocampus was determined using LC-MS/MS. Finally, the mechanisms of catalpol were further assessed in BV2 and PC12 cells in vitro using Western blot, RT-PCR, flow cytometry, molecular docking tests, thermal shift assay, transmission electron microscopy, and immunofluorescence analysis. RESULTS: Behavior tests showed that catalpol therapy could lessen the cognitive impairment induced by LPS damage. HE, Nissl, immunofluorescence, transmission electron microscopy, and Golgi staining further reflected that catalpol treatment could restore lymphocyte infiltration, blood-brain barrier (BBB) degradation, and the decreasing complexity of dendritic trees. According to LC-MS/MS analysis, catalpol had a 136 ng/mg concentration in the hippocampus. In vitro investigation showed that catalpol could inhibit microglia M1 polarization via blocking NF-κB phosphorylation, translocation and then reducing inflammatory cytokine release in BV2 microglia cells. Brain-derived neurotrophic factor (BDNF) release up-regulation and TrkB pathway activation were observed in the catalpol treatment group in vivo and in vitro. The effect of catalpol on enhancing BDNF expression was inhibited by the specific inhibitor of TrkB (GNF-5837) in PC12 cells. Further molecular docking tests showed that catalpol formed weak hydrophobic bonds with TrkB. Besides, thermal shift assay also reflected that catalpol incubation caused a considerable change in the melting temperature of the TrkB. CONCLUSION: Catalpol alleviates LPS-triggered post-sepsis cognitive impairment by reversing neuroinflammation via blocking the NF-κB pathway, up-regulating neurotrophic factors via the activation of TrkB pathway, and preserving BBB integrity.

Flattened chains dominate the adsorption dynamics of loosely adsorbed chains on modified planar substrates.

Herein, the adsorption of polystyrene (PS) on phenyl-modified SiO2-Si substrates was investigated. Different from those for PS adsorption on a neat SiO2-Si substrate, the growth rate (vads) in the linear regime and hads/Rg (hads, thickness of flattened and loosely adsorbed layers on the substrate; Rg, radius of gyration) declined with increasing molecular weight (Mw) of PS and the phenyl content on the modified substrates, while the thickness of the flattened layer (hflat) and its coverage increased with increasing phenyl content. The results indicated that the adsorption of loose chains was controlled by the adsorption of flattened chains, as it only occurred in the empty contact sites remaining after the adsorption of flattened chains. Before approaching quasi-equilibrium (t < tcross), the number of flattened chain contact sites increased due to an enthalpically favorable process and, correspondingly, their spatial positions dynamically changed, which perturbed the adsorption of loose chains. When the adsorption of flattened chains reached quasi-equilibrium (t > tcross), the adsorption of loose chains was determined by the empty contact sites. The coverage of flattened chains and time to reach quasi-equilibrium were increased with more phenyl groups on the substrate, enhancing π-π interfacial interactions and resulting in a decreased adsorption rate and fewer loosely adsorbed chains. Mw-dependent vads and hads/Rg differed on phenyl-modified substrates compared to the neat SiO2-Si substrate owing to fewer empty contact sites for loose chains. The study findings improve our understanding of the mechanism responsible for the formation and structure of the adsorbed layer on solid surfaces.

Catalpol Alleviates Ischemic Stroke Through Promoting Angiogenesis and Facilitating Proliferation and Differentiation of Neural Stem Cells via the VEGF-A/KDR Pathway.

Stroke is one of the leading causes of disability and death globally with a lack of effective therapeutic strategies. Catalpol is a bioactive compound derived from the traditional Chinese medicine Rehmannia glutinosa and it has been shown to be protective against various neurological diseases. The potential roles of catalpol against ischemic stroke are still not completely clear. In this study, we examined the effect and mechanism of catalpol against ischemic stroke using in vivo rat distal middle cerebral artery occlusion (dMCAO) and in vitro oxygen-glucose deprivation (OGD) models. We demonstrated that catalpol indeed attenuated the neurological deficits caused by dMCAO and improved neurological function. Catalpol remarkably promoted angiogenesis, promoted proliferation and differentiation of neural stem cells (NSCs) in the subventricular zone (SVZ), and prevented neuronal loss and astrocyte activation in the ischemic cortex or hippocampal dentate gyrus (DG) in vivo. The vascular endothelial growth factor receptor 2 (KDR, VEGFR-2) inhibitor SU5416 and VEGF-A shRNA were used to investigate the underlying mechanisms. The results showed that SU5416 administration or VEGF-A-shRNA transfection both attenuated the effects of catalpol. We also found that catalpol promoted the proliferation of cultured brain microvascular endothelial cells (BMECs) and the proliferation and differentiation of NSCs subjected to OGD insult in vitro. Interestingly, the impact of catalpol on cultured cells was also inhibited by SU5416. Moreover, catalpol was shown to protect NSCs against OGD indirectly by promoting BMEC proliferation in the co-cultured system. Taken together, catalpol showed therapeutic potential in cerebral ischemia by promoting angiogenesis and NSC proliferation and differentiation. The protective effects of catalpol were mediated through VEGF-A/KDR pathway activation.

Astragalus injection ameliorates lipopolysaccharide-induced cognitive decline via relieving acute neuroinflammation and BBB damage and upregulating the BDNF-CREB pathway in mice.

CONTEXT: Post-sepsis cognitive impairment is one of the major sequelae observed in survivors of sepsis. Astragalus injection is the normally preferred treatment in sepsis in clinical settings. OBJECTIVE: This study evaluated the benefits and related mechanism of Astragalus injection on post-sepsis cognitive impairment. MATERIALS AND METHODS: C57BL/6J mice were divided into three groups: Control, LPS (2.5 mg/kg, i.p.), and LPS + Astragalus injection (5.0 mL/kg). The surviving mice from sepsis were injected with material named Astragalus injection continuously for 13 days. Behavioural tests were first conducted to evaluate the benefits. Second, inflammatory cytokines secretion, BBB integrity, neurodegeneration, and protein expression was evaluated in vivo and in vitro. RESULTS: Compared with the LPS group, mice in Astragalus injection group exhibited shorter escape latency (34.6 s versus 24.5 s) in the Morris water maze test. Treatment with Astragalus injection could reverse LPS-induced neuroinflammation in mice and BV2 cells. Continuous Astragalus injection treatment not only prevented blood-brain barrier dysfunction, but also prevented neurodegeneration. Further molecular docking tests and western blot results reflected that the main constituents of Astragalus injection could interact with TrkB (the estimated binding energy values were -7.0 to -5.0 kcal/mol) and upregulate the protein expression of BDNF/TrkB/CREB signalling pathway during the chronic stage in mice. DISCUSSION: Astragalus injection treatment could reduce neuroinflammation, reverse BBB dysfunction, prevent neurodegeneration, and upregulate BDNF-CREB pathway during LPS-induced sepsis, ultimately preventing the development of cognitive decline. CONCLUSION: Astragalus injection could be a potential preventive and therapeutic strategy for sepsis survivors in clinical settings.

Feasibility of Catalpol Intranasal Administration and Its Protective Effect on Acute Cerebral Ischemia in Rats via Anti-Oxidative and Anti-Apoptotic Mechanisms.

PURPOSE: Catalpol is the main active component of Rehmannia glutinosa, which has a variety of pharmacological activities, including anti-inflammatory and anti-oxidative effects. This study investigates the feasibility of catalpol intranasal administration and its protective effect on acute cerebral ischemia in rats via anti-oxidative and anti-apoptotic mechanisms. PATIENTS AND METHODS: This study investigates the method of catalpol intranasal administration to evaluate the nasal mucosal toxicity, brain targeting and pharmacokinetics of catalpol. The protective effect of catalpol of intranasal administration on stroke-induced brain injury in rats and its mechanisms on oxidative stress pathway Nrf2/HO-1 and apoptosis were also investigated using middle cerebral artery occlusion (MCAO). RESULTS: The results showed that catalpol intranasal administration was safe and feasible with no hemolysis, no bad effect on the maxillary ciliary movement of bullfrog. After intranasal administration, the brain targeting index (DTI) of catalpol was greater than 1, which indicated that catalpol had good brain targeting after intranasal administration. The bioavailability of catalpol administered intranasally was higher than that of in plasma. In MACO model, catalpol intranasal administration could significantly reduce cerebral infarction volume, neurological dysfunction and brain edema. In addition, catalpol intranasal administration can also reduce the brain cell's occurrence of apoptosis, promote the expression of Bcl-2 protein and inhibit the expression of Bax protein, reduce oxidative stress damage via up-regulating expression of Nrf2 and HO-1, increasing the activities of SOD and decreasing the activities of MDA. CONCLUSION: Collectively, catalpol intranasal administration has good safety, stability and brain targeting. It can effectively protect the brain injury of the rat model of acute cerebral ischemia and provide the possibility of drug administration in the acute stage of cerebral ischemia, especially before entering the hospital.

Green Synthesized Gold Nanoparticles Using Viola betonicifolia Leaves Extract: Characterization, Antimicrobial, Antioxidant, and Cytobiocompatible Activities.

INTRODUCTION: Viola betonicifolia is a rich source of numerous secondary metabolites, such as alkaloids, flavonoids, tannins, phenolic compounds, saponins, triterpenoids, and so on, that are biologically active towards different potential biomedical applications. To broaden the potential use of Viola betonicifolia in the realm of bionanotechnology, we investigated the plant's ability to synthesize gold nanoparticles (Au NPs) in a green and efficient manner for the very first time. METHODS: The gold nanoparticles (VB-Au NPs) were synthesized using the leaves extract of Viola betonicifolia, in which plant's secondary metabolites function as both reducing and capping agents. The VB-Au NPs were successfully characterized with spectroscopic techniques. The antimicrobial properties of the VB-Au NPs were further explored against bacterial and mycological species. Additionally, their antioxidant, cytotoxic, and cytobiocompatibility properties were examined in vitro against linoleic acid peroxidation, MCF-7 cancer cells, and human mesenchymal stem cells (hMSCs), respectively. RESULTS: Results demonstrated that VB-Au NPs presented excellent antibacterial, antifungal, and biofilm inhibition performance against all the tested microbial species compared to plant leaves extract and commercially purchased chemically synthesized gold NPs (CH-Au NPs). Moreover, they also exhibited significant antioxidant potential, comparable to the external standard. The VB-Au NPs displayed good cytobiocompatibility with hMSCs and demonstrated excellent cytotoxic potential against MCF-7 cancer cells compared to CH-Au NPs. The current work presents a green method for synthesizing VB-Au NPs with enhanced antioxidant, antimicrobial, cytotoxic and biofilm inhibition efficacy compared to CH-Au NPs might be attributed to the synergistic effect of the nanoparticle's physical properties and the adsorbed biologically active phytomolecules from the plant leaves extract on their surface. CONCLUSION: Thus, our study establishes a novel ecologically acceptable route for nanomaterials' fabrication with increased and/or extra medicinal functions derived from their herbal origins.

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.

Network Pharmacology-Based Prediction of Catalpol and Mechanisms against Stroke.

AIM: To apply the network pharmacology method to screen the target of catalpol prevention and treatment of stroke, and explore the pharmacological mechanism of Catalpol prevention and treatment of stroke. METHODS: PharmMapper, GeneCards, DAVID, and other databases were used to find key targets. We selected hub protein and catalpol which were screened for molecular docking verification. Based on the results of molecular docking, the ITC was used to determine the binding coefficient between the highest scoring protein and catalpol. The GEO database and ROC curve were used to evaluate the correlation between key targets. RESULTS: 27 key targets were obtained by mapping the predicted catalpol-related targets to the disease. Hub genes (ALB, CASP3, MAPK1 (14), MMP9, ACE, KDR, etc.) were obtained in the key target PPI network. The results of KEGG enrichment analysis showed that its signal pathway was involved in angiogenic remodeling such as VEGF, neurotrophic factors, and inflammation. The results of molecular docking showed that ACE had the highest docking score. Therefore, the ITC was used for the titration of ACE and catalpol. The results showed that catalpol had a strong binding force with ACE. CONCLUSION: Network pharmacology combined with molecular docking predicts key genes, proteins, and signaling pathways for catalpol in treating stroke. The strong binding force between catalpol and ACE was obtained by using ITC, and the results of molecular docking were verified to lay the foundation for further research on the effect of catalpol on ACE. ROC results showed that the AUC values of the key targets are all >0.5. This article uses network pharmacology to provide a reference for a more in-depth study of catalpol's mechanism and experimental design.

The Pivotal Role of Microbiota in Modulating the Neuronal-Glial-Epithelial Unit.

The enteric nervous system (ENS) consists of enteric neurons and enteric glial cells (EGCs) and controls the function of the epithelial barrier. Thus, a novel concept of neuronal-glial-epithelial unit in the gut was put forward by analogy with neuronal-glial-endothelial unit in the brain. The environment in the gastrointestinal (GI) tract is complex as it harbours millions of bacteria, which extensively attach with intestinal epithelium. The cross-talk between the neuronal-glial-endothelial unit and microbiota plays a pivotal role in modulating the epithelial barrier's permeability, intestinal development and immune response. And evidence shows dysbiosis is the potent risk factor in the pathologic process of Parkinson's disease (PD) and inflammatory bowel disease (IBD). In this review, we summarize the compelling results in favor of microbiota serving as the key modulator in the neuronal-glial-epithelial unit development and function, with profound effects on intestinal homeostasis.

The Impact of Gut Microbiota Disorders on the Blood-Brain Barrier.

The gut microbiota is symbiotic with the human host and has been extensively studied in recent years resulting in increasing awareness of the effects of the gut microbiota on human health. In this review, we summarize the current evidence for the effects of gut microbes on the integrity of the cerebral blood-brain barrier (BBB), focusing on the pathogenic impact of gut microbiota disorders. Based on our description and summarization of the effects of the gut microbiota and its metabolites on the nervous, endocrine, and immune systems and related signaling pathways and the resulting destruction of the BBB, we suggest that regulating and supplementing the intestinal microbiota as well as targeting immune cells and inflammatory mediators are required to protect the BBB.

[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.

Mutual environmental drivers of the community composition, functional attributes and co-occurrence patterns of bacterioplankton in the composite aquatic ecosystem of Taihu watershed in China.

This study aimed to determine the environmental and ecological factors influencing the planktonic prokaryotic community profiles in the composite ecosystem comprising Taihu Lake, Taipu River and Jinze Reservoir in the Taihu Watershed in China. A total of 42 water samples were intermittently collected from different sites in 6 months across four seasons. Physicochemical characteristics of the ecosystem, bacterioplankton diversity and composition, the presence of co-occurrence patterns, and environmental predictors of ecological modules in the bacterioplankton network were determined. The central species played a more important role in regulating the structure and function of the bacterioplankton community and in responding to environmental contamination than the entire community. The relative abundance of the phylum Proteobacteria and the class Betaproteobacteria varied significantly between months and locations, which were identified as core functional taxa. A non-random co-occurrence pattern and function-driven modular structure were observed in the bacterioplankton co-occurrence network. Dissolved oxygen and ammonium nitrogen were the major and mutual environmental predictors of the bacterioplankton community composition, functional attributes and relative abundance of ecological modules. The results improve our understanding of the impact of anthropogenic contamination on bacterioplankton diversity and biogeochemical cycles and the formulation of strategies for bioremediation of the Taihu Watershed.

Interference from haloacetamides during the determination of haloacetic acids using gas chromatography.

Haloacetic acids (HAAs) are the second largest class of disinfection by-products (DBPs) by weight in water and are more cytotoxic and genotoxic to mammalian cells than trihalomethanes, the first largest class of DBPs. Gas chromatography (GC) is the most widely used technique for determining HAAs. Due to their polar nature, derivatization prior to GC analysis is required. Typically, derivatization is undertaken with acidic methanol, which converts HAAs to the corresponding methyl ester (haloacetic acid methyl esters, abbreviated as HAAMEs), and HAAs are quantified by measuring HAAMEs. In this study, the interference from two other groups of DBPs, the haloacetonitriles (HANs) and haloacetamides (HAMs), on the determination of HAAs was investigated. HANs and HAMs at a range of concentrations (0, 20, 40, 60, 80, and 100 µg/L) were subjected to the same derivatization and analytical procedures as HAAs. The stability of HANs and HAMs under strongly acidic conditions was assessed and the operative mechanism of interference was investigated. The results showed that HAMs significantly interfered with the determination of the corresponding HAAs and the transformation rates of HAMs (representing the extent of HAMs transforming to corresponding HAAMEs) ranged from 6.5 to 45.7%, while the impact of HANs can be neglected. The stability of HANs and HAMs under strongly acidic conditions indicated that hydrolysis was not the cause of the interference. Instead, it was proposed that HAMs react with methyl alcohol, to generate the same corresponding HAAMEs that was generated when HAAs reacted with methyl alcohol. A method for revising HAA concentrations in the presence of HAMs is suggested.

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.

Catalpol may improve axonal growth via regulating miR-124 regulated PI3K/AKT/mTOR pathway in neurons after ischemia.

BACKGROUND: MicroRNA-124 (miR-124) is a brain-specific miRNA molecule, the highest expression in the cortex and is associated with neuronal protection after stroke. This study aimed to investigate whether catalpol could affect miR-124 to regulate PI3K/AKT/mTOR pathway, promoting axonal growth in stroke rats. METHODS: Cells were divided into three groups: control group, miRNA124 agomir group, and miRNA124 antagomir group. To explore the mechanism, cells were divided into seven groups: control group, OGD group (OGD/R), miRNA124 agomir group, miRNA124 agomir plus catalpol group, miRNA124 antagomir group, miRNA124 antagomir plus catalpol group, and catalpol group. Before OGD/R, miRNA124 antagomir and microRNA124 agomir were transfected into neurons for 6 h by using ribo FECT nd Consumablesn/reper transfection kit. Cell survival and cell death were detected by MTT and LDH assay. Axonal growth was assessed by MAP-2 immunofluorescence staining. Western blotting and qPCR were used to detect the expression of molecules in the PI3K/AKT/mTOR pathway. RESULTS: Inhibition of miR-124 activated PI3K/AKT/mTOR pathway and promoted neuronal survival and axonal growth. The expression of miR-124 increased after OGD/R, and catalpol could inhibit miR-124 to activate PI3K/AKT/mTOR pathway to further promote axonal growth. CONCLUSIONS: It is concluded that catalpol may inhibit miR-124 to activate PI3K/AKT/mTOR pathway, promoting axonal growth.