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Buyang Huanwu Decoction (BHD), a classic traditional Chinese medicine (TCM) formula, has been used for recovering neurological dysfunctions and treating post-stroke disability in China for 200 years. In the present study, we investigated the effects of BHD on inhibiting neuronal apoptosis, promoting proliferation and differentiation of neural stem cells (NSCs) and neurite formation and enhancing learning and memory functional recovery in an experimental rat ischemic stroke model. BHD significantly reduced infarct volume and decreased cell apoptosis in the ischemic brain. BHD enhanced neuronal cell viability in vitro. BHD dose-dependently promoted the proliferation of NSCs in ischemic rat brains in vivo. Moreover, BHD promoted neuronal and astrocyte differentiation in primary cultured NSCs in vitro. Water maze test revealed that BHD promoted the recovery of learning function but not memory functions in the transient ischemic rats. We then investigated the changes of the cellular signaling molecules by using two-dimension (2D) gel electrophoresis and focused on the PI3K/Akt/Bad and Jak2/Stat3/cyclin D1signaling pathway to uncover its underlying mechanisms for its neuroprotective and neurogenetic effects. BHD significantly upregulated the expression of p-PI3K, p-Akt, and p-Bad as well as the expression of p-Jak, p-Stat3, and cyclin D1 in vitro and in vivo. In addition, BHD upregulated Hes1 and downregulated cav-1 in vitro and in vivo. Taken together, these results suggest that BHD has neuroprotective effects and neurogenesis-promoting effects via activating PI3K/Akt/Bad and Jak2/Stat3/Cyclin D1 signaling pathways.

Background Over the past few decades, the emergence and maturation of new technologies have substantially reduced the cost of genome sequencing. As a result, the amount of genomic data that needs to be stored and transmitted has grown exponentially. For the standard sequencing data format, FASTQ, compression of the quality score is a key and difficult aspect of FASTQ file compression. Throughout the literature, we found that the majority of the current quality score compression methods do not support random access. Based on the above consideration, it is reasonable to investigate a lossless quality score compressor with a high compression rate, a fast compression and decompression speed, and support for random access. Results In this paper, we propose CMIC, an adaptive and random access supported compressor for lossless compression of quality score sequences. CMIC is an acronym of the four steps (classification, mapping, indexing and compression) in the paper. Its framework consists of the following four parts: classification, mapping, indexing, and compression. The experimental results show that our compressor has good performance in terms of compression rates on all the tested datasets. The file sizes are reduced by up to 21.91% when compared with LCQS. In terms of compression speed, CMIC is better than all other compressors on most of the tested cases. In terms of random access speed, the CMIC is faster than the LCQS, which provides a random access function for compressed quality scores. Conclusions CMIC is a compressor that is especially designed for quality score sequences, which has good performance in terms of compression rate, compression speed, decompression speed, and random access speed. The CMIC can be obtained in the following way: https://github.com/Humonex/Cmic .

Stroke is the second leading cause of death and the third leading cause of disability worldwide, with limited treatment options [...].Stroke is the second leading cause of death and the third leading cause of disability worldwide, with limited treatment options [...].

Myeloperoxidase (MPO) plays critical role in the pathology of cerebral ischemia–reperfusion (I/R) injury via producing hypochlorous acid (HOCl) and inducing oxidative modification of proteins. High-mobility group box 1 (HMGB1) oxidation, particularly disulfide HMGB1 formation, facilitates the secretion and release of HMGB1 and activates neuroinflammation, aggravating cerebral I/R injury. However, the cellular sources of MPO/HOCl in ischemic brain injury are unclear yet. Whether HOCl could promote HMGB1 secretion and release remains unknown. In the present study, we investigated the roles of microglia-derived MPO/HOCl in mediating HMGB1 translocation and secretion, and aggravating the brain damage and blood-brain barrier (BBB) disruption in cerebral I/R injury. In vitro, under the co-culture conditions with microglia BV cells but not the single culture conditions, oxygen–glucose deprivation/reoxygenation (OGD/R) significantly increased MPO/HOCl expression in PC12 cells. After the cells were exposed to OGD/R, MPO-containing exosomes derived from BV2 cells were released and transferred to PC12 cells, increasing MPO/HOCl in the PC12 cells. The HOCl promoted disulfide HMGB1 translocation and secretion and aggravated OGD/R-induced apoptosis. In vivo, SD rats were subjected to 2 h of middle cerebral artery occlusion (MCAO) plus different periods of reperfusion. Increased MPO/HOCl production was observed at the reperfusion stage, accomplished with enlarged infarct volume, aggravated BBB disruption and neurological dysfunctions. Treatment of MPO inhibitor 4-aminobenzoic acid hydrazide (4-ABAH) and HOCl scavenger taurine reversed those changes. HOCl was colocalized with cytoplasm transferred HMGB1, which was blocked by taurine in rat I/R-injured brain. We finally performed a clinical investigation and found that plasma HOCl concentration was positively correlated with infarct volume and neurological deficit scores in ischemic stroke patients. Taken together, we conclude that ischemia/hypoxia could activate microglia to release MPO-containing exosomes that transfer MPO to adjacent cells for HOCl production; Subsequently, the production of HOCl could mediate the translocation and secretion of disulfide HMGB1 that aggravates cerebral I/R injury. Furthermore, plasma HOCl level could be a novel biomarker for indexing brain damage in ischemic stroke patients.

Background Hemorrhagic transformation (HT) is a common complication of delayed tissue plasminogen activator (t-PA) treatment for ischemic stroke. Peroxynitrite plays an important role in the breakdown of blood–brain barrier (BBB) and the development of HT. We tested the hypothesis that Angong Niuhuang Wan (AGNHW), a traditional Chinese medicinal formula, could be used in conjunction with t-PA to protect the BBB, minimize HT, and improve neurological function by suppressing peroxynitrite-mediated matrix metalloproteinase-9 (MMP-9) activation. Methods We first performed quality control study and chemical identification of AGNHW by using UPLC. In animal experiments, male Sprague–Dawley rats were subjected to 5 h of middle cerebral artery occlusion (MCAO) followed by 19 h of reperfusion plus t-PA infusion (10 mg/kg) at 5 h of cerebral ischemia. AGNHW (257 mg/kg) was given orally at 2 h after MCAO. Hemorrhagic transformation was measured using hemorrhagic scores and hemoglobin levels in ischemic brains. Evans blue leakage was utilized to assess the severity of the blood–brain barrier (BBB) damage. The modified neurologic severity score (mNSS) test was used to assess neurological functions. Peroxynitrite and superoxide was detected by using fluorescent probes. MMP-9 activity and expression were examined by gelatin zymography and immunostaining. The antioxidant effects were also studied by using brain microvascular endothelial b.End3 cells exposed to 5 h of oxygen and glucose deprivation (OGD) plus 5 h of reoxygenation with t-PA treatment (20 µg/ml). Results AGNHW significantly reduced the BBB damage, brain edema, reduced hemorrhagic transformation, enhanced neurological function, and reduced mortality rate in the ischemic stroke rats with t-PA treatment. AGNHW reduced peroxynitrite and superoxide in vivo and in vitro and six active chemical compounds were identified from AGNHW with peroxynitrite scavenging activity. Furthermore, AGNHW inhibited MMP-9 activity, and preserved tight junction protein claudin-5 and collagen IV in the ischemic brains. Conclusion AGNHW could be a potential adjuvant therapy with t-PA to protect the BBB integrity, reduce HT, and improve therapeutic outcome in ischemic stroke treatment via inhibiting peroxynitrite-mediated MMP-9 activation. Graphical Abstract

Danggui-Shayao-San (DSS) is a famous Traditional Chinese Medicine formula that used for treating pain disorders and maintaining neurological health. Recent studies indicate that DSS has neuroprotective effects against ischemic brain damage but its underlining mechanisms remain unclear. Herein, we investigated the neuroprotective mechanisms of DSS for treating ischemic stroke. Adult male Sprague-Dawley (S.D.) rats were subjected to 2 h of middle cerebral artery occlusion (MCAO) plus 22 h of reperfusion. Both ethanol extract and aqueous extract of DSS (12 g/kg) were orally administrated into the rats at 30 min prior to MCAO ischemic onset. We found that 1) ethanol extract of DSS, instead of aqueous extract, reduced infarct sizes and improved neurological deficit scores in the post-ischemic stroke rats; 2) Ethanol extract of DSS down-regulated the expression of the cleaved-caspase 3 and Bax, up-regulated bcl-2 and attenuated apoptotic cell death in the ischemic brains; 3) Ethanol extract of DSS decreased the production of superoxide and peroxynitrite; 4) Ethanol extract of DSS significantly down-regulated the expression of p67 phox but has no effect on p47 phox and iNOS statistically. 5) Ethanol extract of DSS significantly up-regulated the expression of SIRT1 in the cortex and striatum of the post-ischemic brains; 6) Co-treatment of EX527, a SIRT1 inhibitor, abolished the DSS’s neuroprotective effects. Taken together, DSS could attenuate oxidative/nitrosative stress and inhibit neuronal apoptosis against cerebral ischemic-reperfusion injury via SIRT1-dependent manner.

In this Research Topic,Li et al.provided a review of the commonly used animal model of depression and antidepressant activity and the mechanism of active components in Panax Notoginseng. [...]natural products have the potential to complement stem cell therapies, offering solutions for traditional treatments-resistant disorders. In summary, this Research Topic underscores the significant promise of natural products in addressing neurological disorders and highlights the need for ongoing research and clinical exploration to fully realize their therapeutic potential.

An intrinsic conflict between high deformability and rigidity hinders the development of electroactive polymer (EAP)-based soft robots. Here, we employ an external electric field to align Al 2 O 3 -coated carbon nanotubes (Al 2 O 3 @CNTs) in a poly(vinylidene fluoride-trifluoroethylene-chlorotrifluoroethylene) (P(VDF-TrFE-CTFE)) matrix. Compared with pure P(VDF-TrFE-CTFE), the thickness strain of nanocomposites with horizontally and vertically aligned Al 2 O 3 @CNTs increases by 473% and 814%, respectively. It results in a high bending angle up to 215° for their actuator beams. Importantly, the horizontally aligned Al 2 O 3 @CNTs enhance the local stiffness via ‘face-enhanced effect’, yielding a high output force per unit volume (1.25 mN/mm 3 at 30 V/μm). It is not only ~346% higher than pure P(VDF-TrFE-CTFE) but also higher than the reported ceramic actuators. Accordingly, the soft robots made by the designed nanocomposite actuators could climb slopes up to 52° and carry loads equivalent to eight times their body mass. Consequently, this modulating strategy develops a high-performance actuation for soft robots. Electroactive polymers can be used for soft robotics, though it is challenging to balance rigidity and deformability. Here the authors designed a polymer composite using an electric-field assisted tape-casting method to orient the Al 2 O 3 -coated carbon nanotubes to tailor the dielectric and mechanical properties.

Background/Objectives: Bone metastasis is a common and severe complication of lung adenocarcinoma (LUAD), impacting prognosis and treatment outcomes. Understanding the molecular mechanisms behind LUAD bone metastasis (LUADBM) is essential for developing new therapeutic strategies. The interactions between long non-coding RNAs (lncRNAs), microRNAs (miRNAs), and mRNAs in the competing endogenous RNA (ceRNA) network are crucial in cancer progression and metastasis, but the regulatory mechanisms in LUADBM remain unclear. Methods: Microarray analysis was performed on clinical samples, followed by weighted gene co-expression network analysis (WGCNA) and construction of a ceRNA network. Molecular mechanisms were validated using colony formation assays, transwell migration assays, wound healing assays to assess cell migration, and osteoclastogenesis assays to evaluate osteoclast differentiation. Potential therapeutic drugs and their binding affinities were predicted using the CMap database and Kdeep. The interaction between the small-molecule drug and its target protein was confirmed by surface plasmon resonance (SPR) and drug affinity responsive target stability (DARTS) assays. Mechanistic insights and therapeutic efficacy were further validated using patient-derived organoid (PDO) cultures, drug sensitivity assays, and in vivo drug treatments. Results: Our results identified the XLOC_006941/hsa-miR-543/NPRL3 axis as a key regulatory pathway in LUADBM. We also demonstrated that GATA3-driven Th2 cell infiltration creates an immunosuppressive microenvironment that promotes metastasis. Additionally, we confirmed that the inhibitor E7449 effectively targets NPRL3, and its combination with the IL4R-blocking antibody dupilumab resulted in improved therapeutic outcomes in LUADBM. Conclusions: These findings offer new insights into the molecular mechanisms of LUADBM and highlight potential therapeutic targets, including the XLOC_006941/miR-543/NPRL3 axis and GATA3-driven Th2 cell infiltration. The dual-target therapy combining E7449 with dupilumab shows promise for improving patient outcomes in LUADBM, warranting further clinical evaluation.

Radix Astragali (AR) is a commonly used medicinal herb for post-stroke disability in Traditional Chinese Medicine but its active compounds for promoting neurogenic effects are largely unknown. In the present study, we tested the hypothesis that Astragaloside VI could be a promising active compound from AR for adult neurogenesis and brain repair via targeting epidermal growth factor (EGF)-mediated MAPK signaling pathway in post-stroke treatment. By using cultured neural stem cells (NSCs) and experimental stroke rat model, we investigated the effects of Astragaloside VI on inducing NSCs proliferation and self-renewal in vitro, and enhancing neurogenesis for the recovery of the neurological functions in post-ischemic brains in vivo. For animal experiments, rats were undergone 1.5 h middle cerebral artery occlusion (MCAO) plus 7 days reperfusion. Astragaloside VI (2 μg/kg) was daily administrated by intravenous injection (i.v.) for 7 days. Astragaloside VI treatment promoted neurogenesis and astrogenic formation in dentate gyrus zone, subventricular zone, and cortex of the transient ischemic rat brains in vivo. Astragaloside VI treatment enhanced NSCs self-renewal and proliferation in the cultured NSCs in vitro without affecting NSCs differentiation. Western blot analysis showed that Astragaloside VI up-regulated the expression of nestin, p-EGFR and p-MAPK, and increased neurosphere sizes, whose effects were abolished by the co-treatment of EGF receptor inhibitor gefitinib and ERK inhibitor PD98059. Behavior tests revealed that Astragaloside VI promoted the spatial learning and memory and improved the impaired motor function in transient cerebral ischemic rats. Taken together, Astragaloside VI could effectively activate EGFR/MAPK signaling cascades, promote NSCs proliferation and neurogenesis in transient cerebral ischemic brains, and improve the repair of neurological functions in post-ischemic stroke rats. Astragaloside VI could be a new therapeutic drug candidate for post-stroke treatment.