Tumor microenvironment responsive nano-platform for overcoming sorafenib resistance of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a malignant tumor, which seriously jeopardizes human health. The 5-year relative survival rate of HCC is only about 18%. Sorafenib, a small molecule multi-targeted tyrosine kinase inhibitor (MTKI), has been classified as the first-line treatment scheme for HCC and has significantly extended the median survival time for patients with advanced HCC. Nevertheless, the emergence of sorafenib resistance has substantially hampered its further clinical application. Herein, the nano-platform based on phototherapy and small molecular targeted therapy (SMTT) was devised to overcome the sorafenib resistance and reduce the adverse effects. Hollow mesoporous manganese dioxide (H-MnO2) was prepared by hard template method, and the prepared H-MnO2 was used to load sorafenib and Chlorin e6 (Ce6). Subsequently, the nanoparticle (NPs) were modified with dopamine to optimize biocompatibility. The final prepared NPs (MCS NPs) exhibit regular spherical shape with a hydrated particle size of approximately 97.02 nm. MCS NPs can not only possess tumor microenvironment (TME) stimuli-responsive drug release performance but also can enhance the efficacy of photodynamic therapy and reverse sorafenib resistance by alleviating tumor hypoxia. Under the action of phototherapy (Ce6) combined with molecular targeted therapy (sorafenib), MCS NPs manifest a satisfactory antitumor effect for sorafenib-sensitive or sorafenib-resistant HCC cells, and retain the antiangiogenic properties of sorafenib. In the nude mouse subcutaneous tumor model constructed with sorafenib-resistant cells, MCS NPs demonstrated superior tumor imaging ability and excellent biocompatibility. The tumor inhibition rate of the MCS NPs group without laser irradiation was 53.4 %, while the MCS NPs group with laser irradiation was as high as 100 %. The novel smart TME-responsive nano-platform shows great potential for overcoming sorafenib resistance and realizes multimodality imaging and therapy of HCC.

Stand Up to Stand Out: Natural Dietary Polyphenols Curcumin, Resveratrol, and Gossypol as Potential Therapeutic Candidates against Severe Acute Respiratory Syndrome Coronavirus 2 Infection.

The COVID-19 pandemic has stimulated collaborative drug discovery efforts in academia and the industry with the aim of developing therapies and vaccines that target SARS-CoV-2. Several novel therapies have been approved and deployed in the last three years. However, their clinical application has revealed limitations due to the rapid emergence of viral variants. Therefore, the development of next-generation SARS-CoV-2 therapeutic agents with a high potency and safety profile remains a high priority for global health. Increasing awareness of the "back to nature" approach for improving human health has prompted renewed interest in natural products, especially dietary polyphenols, as an additional therapeutic strategy to treat SARS-CoV-2 patients, owing to its good safety profile, exceptional nutritional value, health-promoting benefits (including potential antiviral properties), affordability, and availability. Herein, we describe the biological properties and pleiotropic molecular mechanisms of dietary polyphenols curcumin, resveratrol, and gossypol as inhibitors against SARS-CoV-2 and its variants as observed in in vitro and in vivo studies. Based on the advantages and disadvantages of dietary polyphenols and to obtain maximal benefits, several strategies such as nanotechnology (e.g., curcumin-incorporated nanofibrous membranes with antibacterial-antiviral ability), lead optimization (e.g., a methylated analog of curcumin), combination therapies (e.g., a specific combination of plant extracts and micronutrients), and broad-spectrum activities (e.g., gossypol broadly inhibits coronaviruses) have also been emphasized as positive factors in the facilitation of anti-SARS-CoV-2 drug development to support effective long-term pandemic management and control.

Guijiajiao (Colla Carapacis et Plastri, CCP) prevents male infertility via gut microbiota modulation.

Male infertility is a significant cause of psychosocial and marital distress in approximately 50% of couples who are unable to conceive, with male factors being the underlying cause. Guijiajiao (Colla Carapacis et Plastri, CCP) is a Traditional Chinese Medicine commonly used to treat male infertility. The present study aimed to investigate the potential mechanisms underlying the preventive effects of CCP on male infertility. An infertile male rat model was established using cyclophosphamide (CTX), and CCP was administered for both treatment and prevention. Fecal microbiota transplantation (FMT) was also performed to explore the role of gut microbiota in the CCP-mediated prevention of male infertility in rats. Sperm motility and concentration were determined using a semi-automatic sperm classification analyzer. Subsequently, histopathological analysis using HE staining was performed to examine the changes in the small intestine and testis. Moreover, the serum levels of lipopolysaccharide (LPS) and testosterone were measured by ELISA. In addition, immunohistochemistry was conducted to detect CD3 expression in the small intestine, while RT-qPCR was employed to assess the expressions of interleukin-1 beta (IL-1ß), cluster of differentiation 3 (CD3), Monocyte chemoattractant protein-1 (MCP-1), and C-X-C motif chemokine ligand 10 (CXCL-10) in the small intestine and epididymis. Finally, gut microbiota was analyzed by 16S rRNA sequencing. CCP improved sperm motility, number, and concentration in CTX-induced infertile male rats. CCP increased the serum testosterone level, inhibited the immune cell infiltration of the intestinal lamina propria, and promoted the aggregation of CD3+ T cells in CTX-induced male infertility rats. CCP also inhibited the expressions of MCP-1, CXCL-10, and IL-1ß in the epididymis of male infertility rats. At the genus level, CTX led to a reduction in the abundance of Lactobacillus, Clostridia_UCG.014, and Romboutsia in the intestinal tract of rats. In contrast, CCP decreased the abundance of Ruminococcus and increased the abundance of Romboutsia in infertile male rats. Additionally, FMT experiments proved that the gut microbiota of CCP-treated rats facilitated testicular tissue recovery and spermatogenesis while also reducing the serum LPS level in infertile male rats. CCP improves the spermatogenic ability of infertile male rats by restoring gut microbiota diversity and inhibiting epididymal inflammation.

An extensive pharmacological evaluation of novel anti-nociceptive and IL-6 targeted anti-inflammatory guaiane-type sesquiterpenoids from Cinnamomum migao H. W. Li through in-depth in-vitro, ADMET, and molecular docking studies.

Guaiane-type sesquiterpenoids are most prevalent in the genus Cinnamomum. Hence this study investigates the structures, anti-nociceptive and IL-6 targeted anti-inflammatory potential of three novels C-14 guaiane-type sesquiterpenoids and two new monoterpenoids, isolated from Cinnamomum migao. The structures were precisely confirmed and characterized through the modern chromatographic and spectroscopic techniques of HRESIMS, 1D NMR, 2D NMR, experimental circular dichroism (ECD), and calculated (ECD). Novel sesquiterpenoids 1 and 2 exhibited significant anti-inflammatory activities against the NO production and pro-inflammatory cytokines. Their IC50 values were determined as 9.52 and 13.42 µΜ against IL-6 mRNA, respectively. Similarly, subcutaneous injection of n-BuT and EA extracts showed a dose-dependent suppression of formalin-induced tonic biting/licking responses during the tonic antinociceptive phase. Furthermore, absorption, distribution, metabolism, excretion, and toxicity (ADMET) analysis of guaiane-type sesquiterpenoids 1 and 2 displayed that both compounds have a high level of GIT absorption, with a high zone of safety for cardiac and hepatotoxicity and no inhibition of cytochromes. In addition, molecular docking and simulation studies strengthen the anti-inflammatory potential of sesquiterpene 2 which showed a good binding affinity with IL-6 protein. Overall the inclusive results showed that the extracts and newly isolated guaiane-type sesquiterpenoids from C. migao will provide new evidence for the traditional use of this species to treat inflammation and nociception.

Arabidopsis pollen-specific glycerophosphodiester phosphodiesterase-like genes are essential for pollen tube tip growth.

In angiosperms, pollen tube growth is critical for double fertilization and seed formation. Many of the factors involved in pollen tube tip growth are unknown. Here, we report the roles of pollen-specific GLYCEROPHOSPHODIESTER PHOSPHODIESTERASE-LIKE (GDPD-LIKE) genes in pollen tube tip growth. Arabidopsis thaliana GDPD-LIKE6 (AtGDPDL6) and AtGDPDL7 were specifically expressed in mature pollen grains and pollen tubes and green fluorescent protein (GFP)-AtGDPDL6 and GFP-AtGDPDL7 fusion proteins were enriched at the plasma membrane at the apex of forming pollen tubes. Atgdpdl6 Atgdpdl7 double mutants displayed severe sterility that was rescued by genetic complementation with AtGDPDL6 or AtGDPDL7. This sterility was associated with defective male gametophytic transmission. Atgdpdl6 Atgdpdl7 pollen tubes burst immediately after initiation of pollen germination in vitro and in vivo, consistent with the thin and fragile walls in their tips. Cellulose deposition was greatly reduced along the mutant pollen tube tip walls, and the localization of pollen-specific CELLULOSE SYNTHASE-LIKE D1 (CSLD1) and CSLD4 was impaired to the apex of mutant pollen tubes. A rice pollen-specific GDPD-LIKE protein also contributed to pollen tube tip growth, suggesting that members of this family have conserved functions in angiosperms. Thus, pollen-specific GDPD-LIKEs mediate pollen tube tip growth, possibly by modulating cellulose deposition in pollen tube walls.

Multifunctional Nanoplatform Based on Sunitinib for Synergistic Phototherapy and Molecular Targeted Therapy of Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is a tumor that poses a serious threat to human health, with an extremely low five-year survival rate due to its difficulty in early diagnosis and insensitivity to radiotherapy and chemotherapy. To improve the therapeutic efficiency of HCC, we developed a novel multifunctional nanoplatform (SCF NPs) with an amphiphilic polymer (Ce6-PEG2000-FA) and a multitarget tyrosine kinase inhibitor sunitinib. SCF NPs showed superior therapeutical efficiency for HCC due to the synergetic effect of molecular targeted therapy and phototherapy. The Ce6-PEG2000-FA not only serves as a nanocarrier with excellent biocompatibility but also can act as a therapeutic reagent for photothermal therapy (PTT) and photodynamic therapy (PDT). Furthermore, the folic acid group of Ce6-PEG2000-FA enhanced the active targeting performance of SCF NPs. As a multitargeted tyrosine kinase inhibitor, sunitinib in SCF NPs can play a role in molecular targeted therapies, including tumor growth inhibition and anti-angiogenesis. In vivo experiments, SCF NPs showed multimode imaging capabilities, which can be used for tumorous diagnosis and intraoperative navigation. Meanwhile, SCF NPs showed outstanding synergetic tumor inhibition ability. Tumors of SCF NPs group with laser radiation were eradicated without any recrudescence after 14 days of treatment. Such theranostic nanoparticles offer a novel therapeutic tactic for HCC.

Neoisoastilbin Ameliorates Acute Gouty Arthritis via Suppression of the NF-κB/NLRP3 Pathway.

Acute gouty arthritis (AGA) is an acute inflammatory disease, whose occurrence and development mechanism are associated with inflammatory reaction of joint tissue. This study investigated the role of neoisoastilbin (NIA) in the treatment of AGA and explored the underlying mechanisms. C57BL/6 mice underwent intraarticular injection of monosodium urate (MSU) to establish an AGA model in vivo. Enzyme-linked immunosorbent assay, histopathological hematoxylin-eosin staining, western blotting, and other methods were used to observe the therapeutic effects of NIA on AGA and investigate the role of the NF-κB/NLRP3 pathway in the treatment. We found that NIA effectively reduced MSU-induced joint swelling and inflammatory cell infiltration in a concentration-dependent manner. NIA also significantly reduced interleukin-1ß (IL-1ß), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) levels as compared with the respective values in the model mice group. In addition, administration of NIA significantly mitigated the phosphorylation of NF-κB-related proteins (IKKα, NF-κB, and IκBα) and the expression of NLRP3-related proteins (NLRP3, caspase-1, and ASC) in MSU-induced joint tissues. In conclusion, our research indicated that NIA significantly improved AGA, and its underlying mechanism was achieved by simultaneously inhibiting the NF-κB/NLRP3 pathway and the expression of inflammatory factors. This research preliminarily suggested the potential role of NIA in the treatment of AGA.

Xin-Li-Fang efficacy and safety for patients with chronic heart failure: A study protocol for a randomized, double-blind, and placebo-controlled trial.

Introduction: Xin-Li-Fang (XLF), a representative Chinese patent medicine, was derived from years of clinical experience by academician Chen Keji, and is widely used to treat chronic heart failure (CHF). However, there remains a lack of high-quality evidence to support clinical decision-making. Therefore, we designed a randomized controlled trial (RCT) to evaluate the efficacy and safety of XLF for CHF. Methods and design: This multicenter, double-blinded RCT will be conducted in China. 300 eligible participants will be randomly assigned to either an XLF group or a control group at a 1:1 ratio. Participants in the XLF group will receive XLF granules plus routine care, while those in the control group will receive placebo granules plus routine care. The study period is 26 weeks, including a 2-week run-in period, a 12-week treatment period, and a 12-week follow-up. The primary outcome is the proportion of patients whose serum NT-proBNP decreased by more than 30%. The secondary outcomes include quality of life, the NYHA classification evaluation, 6-min walking test, TCM symptom evaluations, echocardiography parameters, and clinical events (including hospitalization for worsening heart failure, all-cause death, and other major cardiovascular events). Discussion: The results of the study are expected to provide evidence of high methodological and reporting quality on the efficacy and safety of XLF for CHF. Clinical trial registration: Chinese Clinical Trial Registration Center (www.chictr.org.cn). The trial was registered on 13 April 2022 (ChiCTR2200058649).

LOX-1 Regulation in Anti-atherosclerosis of Active Compounds of Herbal Medicine: Current Knowledge and the New Insight.

Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) have recently been identified to be closely related to the occurrence and development of atherosclerosis (AS). A growing body of evidence has suggested Chinese medicine takes unique advantages in preventing and treating AS. In this review, the related research progress of AS and LOX-1 has been summarized. And the anti-AS effects of 10 active components of herbal medicine through LOX-1 regulation have been further reviewed. As a potential biomarker and target for intervention in AS, LOX-1 targeted therapy might provide a promising and novel approach to atherosclerotic prevention and treatment.

Nanomaterials based on phase change materials for antibacterial application.

Bacterial infections seriously threaten human health. Although antibiotics can significantly treat infectious diseases, antibiotics abuse has brought a series of serious problems, such as multidrug-resistant bacteria, adverse effects, and so on. Therefore, it is indispensable to develop alternative therapies with superior efficacy and minor toxicity to enhance the anti-infective outcome, overcome drug resistance and reduce adverse effects. The phase change material (PCM) is a substance that changes its physical properties with elevated temperatures. Nanoparticles based on PCM have been widely used in biomedical research due to their excellent biocompatibility, sustained release, and outstanding targeting properties. In this manuscript, the applications of PCM-based nanoparticles in the treatment of bacterial infections were summarized. Firstly, the composition and biotoxicity of PCM nanocarriers were described. Secondly, various antibacterial strategies based on PCM nanoparticles for combination therapy were highlighted. Finally, the prospects for antibacterial therapy of PCM nanomaterials were summarized.

Metabolism disorder promotes isoproterenol-induced myocardial injury in mice with high temperature and high humidity and high-fat diet.

BACKGROUND: Isoproterenol (ISO), a synthetic on selective ß-adrenergic agonist, provides a simple and non-invasive method for inducing myocardial injury with lower mortality and higher reproducibility. Phlegm-damp syndrome, as known as "Tanshi" in Chinese, is one of Traditional Chinese Medicine (TCM) syndrome differentiation, which plays an important role in the development of cardiovascular diseases. However, the underlying mechanism remains unknown. METHODS: In our present study, a myocardial injury mouse model was introduced by ISO administration combined with high temperature and high humidity and high-fat diet to simulate phlegm-damp syndrome. Nontargeted metabolomics with LC-MS/MS was adopted to reveal serum metabolism profile for elucidating the possible molecular mechanism. RESULTS: The results of our study showed that phlegm-damp syndrome promoted ISO-induced myocardial injury by aggravating left ventricular hypertrophy and fibrosis, and increasing cardiac index. Our study also confirmed the presence of specific metabolites and disturbed metabolic pathways by comparing ISO mice and Tanshi mice, mainly including glycerophospholipid metabolism, arginine-proline metabolism, and sphingolipid signaling pathway. The lysoPCs, PCs, SMs, Sphingosine, and L-Arginine were the main metabolites that showed a difference between ISO and Tanshi mice, which might be the result of the underlying mechanism in the promotion of ISO-induced myocardial injury in mice with high temperature and high humidity and high-fat diet. CONCLUSION: Our current study provides new insights into contribution of metabolism disorder in promotion of ISO-induced myocardial injury in mice with high temperature and high humidity and high-fat diet, and new targets for clinical diagnosis and pharmacologic treatment of cardiovascular disease with phlegm-damp syndrome.

Astragaloside IV inhibits hepatocellular carcinoma by continually suppressing the development of fibrosis and regulating pSmad3C/3L and Nrf2/HO-1 pathways.

ETHNOPHARMACOLOGICAL RELEVANCE: Astragalus is a medicinal herb used in China for the prevention and treatment of diseases such as diabetes and cancer. As one of the main active ingredients of astragalus, Astragaloside IV (AS-IV) has a wide range of pharmacological effects, including anti-inflammation and anti-cancer effects. AIM OF THE STUDY: Different phosphorylated forms of Smad3 differentially regulate the progression of hepatic carcinoma. The phosphorylation of the COOH-terminal of Smad3 (pSmad3C) and activation of the Nrf2/HO-1 pathway inhibits hepatic carcinoma, while phosphorylation of the linker region of Smad3 (pSmad3L) promotes progression. Thus, pSmad3C/3L and Nrf2/HO-1 pathways are potential targets for drug of anti-cancer development. AS-IV is anti-apoptotic and can inhibit hepatocellular carcinoma cell (HCC) proliferation, invasion, and tumor growth in nude mice. However, it is not clear whether AS-IV has a therapeutic effect on inhibiting the progression of primary liver cancer by regulating the pSmad3C/3L and Nrf2/HO-1 pathway. The purpose of this study is to investigate whether AS-IV inhibits hepatocellular carcinoma by regulating pSmad3C/3L and Nrf2/HO-1 pathway. MATERIALS AND METHODS: primary liver cancer in mice induced by DEN/CCl4/C2H5OH (DCC) and HSC-T6/HepG2 cell models activated by TGF-ß1 was investigated for the mechanisms of AS-IV. In vivo assays included liver biopsy, histopathology and post-mortem analysis included immunohistochemistry, immunofluorescent, and Western blotting analysis, and in vitro assays included immunofluorescent, and Western blotting analysis. RESULTS: AS-IV significantly inhibited the development of primary liver cancer, reflecting improved liver biopsy, histopathology. The incidence and multiplicity of primary liver cancer were markedly decreased by AS-IV treatment at the 20th week. AS-IV had observable effects on the TGF-ß1/Smad and Nrf2/HO-1 expression in vivo, especially up-regulated pSmad3C, pNrf2, HO-1, and NQO1, while it down-regulated pSmad2C, pSmad2L, pSmad3L, PAI-1, and α-SMA at the 12th week and the 20th week. Furthermore, in vitro analysis further confirmed that AS-IV regulated the expression of pSmad3C/3L and Nrf2/HO-1 pathway in HSC-T6 and HepG2 cells activated by TGF-ß1. CONCLUSION: AS-IV administration delays the occurrence of primary liver cancer by continually suppressing the development of fibrosis, the mechanism of the therapeutic effect involving the regulation of the pSmad3C/3L and Nrf2/HO-1 pathways, especially in regulation reversibility and antagonism of pSmad3C and pSmad3L and promoting the phosphorylation of Nrf2.

Chemical profiling of Dioscorea septemloba by High Performance Liquid Chromatography Coupled to Electrospray Ionization and Quadrupole Time-of-Flight Mass Spectrometry.

The rhizomes of Dioscorea septemloba (DS) is one of traditional Chinese medicine, which can be used for treatments of urethral and renal infections, as well as rheumatism. Nevertheless, detailed information on DS chemical compositions is still scarce. Therefore, the present work is aimed at investigating the phytochemical components of DS using high performance liquid chromatography coupled to electrospray ionization and quadrupole time-of-flight mass spectrometry in negative ion mode. The proposed method provided tentative identification of 32 components, 6 of which were determined to be new. The present study highlighted the importance of DS as a promising source of medicinal ingredients and provides valuable information on the new potential components in DS.

Fe-Doped Polyoxometalate as Acid-Aggregated Nanoplatform for NIR-II Photothermal-Enhanced Chemodynamic Therapy.

The combination of reactive oxygen species-involved chemodynamic therapy (CDT) and photothermal therapy (PTT) holds great promise in enhancing anticancer effects. Herein, a multifunctional Fe-doped polyoxometalate (Fe-POM) cluster is fabricated via a simple method. The Fe-POM can not only be utilized as PTT agents to generate a hyperthermia effect for cancer cell killing under near-infrared (NIR) II laser (1060 nm) irradiation, but also can be used as CDT agents to convert endogenous less-reactive H2 O2 into harmful ·OH and simultaneously deplete glutathione for an amplified CDT effect. Notably, the hyperthermia induced by PTT can further enhance the CDT effect, achieving a synergistic PTT/CDT effect. Owing to the self-assembling properties at lowered pH values, the Fe-POM exhibits high tumor accumulation as revealed by photoacoustic imaging. More importantly, Fe-POM enables effective destruction of tumors without inducing noticeable damage to normal tissues under 1060 nm laser irradiation. The work presents a new type of multifunctional agent with high PTT/CDT efficacy, providing promising methods for PTT-enhanced CDT in a NIR-II biowindow.

Near-Infrared Light-Harvesting Fullerene-Based Nanoparticles for Promoted Synergetic Tumor Phototheranostics.

A synergetic phototheranostic system, combining diagnostic photo-imaging and phototherapies [such as photothermal therapy and photodynamic therapy (PDT)], shows great potential in today's tumor precise therapy. Herein, we fabricate near-infrared (NIR) light-harvesting fullerene-based nanoparticles (DAF NPs) for photoacoustic (PA) imaging-guided synergetic tumor photothermal and PDT. The fullerene derivatives (DAF) absorbing in the NIR region have been synthesized by conjugating NIR-absorbing antenna with fullerene. In addition, DAF NPs with good biocompatibility have been fabricated via a nanoprecipitation approach. The as-prepared DAF NPs can accumulate and generate PA signals around the tumor site 6 h post injection via enhanced permeability and retention effect in vivo. More importantly, the DAF NPs exhibit better reactive oxygen species and heat generation efficacy compared with fullerene and antenna nanoparticles (DA NPs), respectively. Further in vitro and in vivo studies demonstrate that DAF NPs can effectively inhibit tumor growth through synergetic photodynamic and photothermal therapies, which provides a new sight of photosensitizer design for enhanced cancer phototheranostics.

Selenium-Modified Microgels as Bio-Inspired Oxidation Catalysts.

Active colloidal catalysts inspired by glutathione peroxidase (GPx) were synthesized by integration of catalytically active selenium (Se) moieties into aqueous microgels. A diselenide crosslinker (Se X-linker) was successfully synthesized and incorporated into microgels through precipitation polymerization, along with the conventional crosslinker N,N'-methylenebis(acrylamide) (BIS). Diselenide bonds within the microgels were cleaved through oxidation by H2 O2 and converted to seleninic acid whilst maintaining the intact microgel microstructure. Through this approach catalytically active microgels with variable amounts of seleninic acid were synthesized. Remarkably, the microgels exhibited higher catalytic activity and selectivity at low reaction temperatures than the molecular Se catalyst in a model oxidation reaction of acrolein to acrylic acid and methyl acrylate.

Stretchable Transparent Electrode Arrays for Simultaneous Electrical and Optical Interrogation of Neural Circuits in Vivo.

Recent developments of transparent electrode arrays provide a unique capability for simultaneous optical and electrical interrogation of neural circuits in the brain. However, none of these electrode arrays possess the stretchability highly desired for interfacing with mechanically active neural systems, such as the brain under injury, the spinal cord, and the peripheral nervous system (PNS). Here, we report a stretchable transparent electrode array from carbon nanotube (CNT) web-like thin films that retains excellent electrochemical performance and broad-band optical transparency under stretching and is highly durable under cyclic stretching deformation. We show that the CNT electrodes record well-defined neuronal response signals with negligible light-induced artifacts from cortical surfaces under optogenetic stimulation. Simultaneous two-photon calcium imaging through the transparent CNT electrodes from cortical surfaces of GCaMP-expressing mice with epilepsy shows individual activated neurons in brain regions from which the concurrent electrical recording is taken, thus providing complementary cellular information in addition to the high-temporal-resolution electrical recording. Notably, the studies on rats show that the CNT electrodes remain operational during and after brain contusion that involves the rapid deformation of both the electrode array and brain tissue. This enables real-time, continuous electrophysiological monitoring of cortical activity under traumatic brain injury. These results highlight the potential application of the stretchable transparent CNT electrode arrays in combining electrical and optical modalities to study neural circuits, especially under mechanically active conditions, which could potentially provide important new insights into the local circuit dynamics of the spinal cord and PNS as well as the mechanism underlying traumatic injuries of the nervous system.

1,3,7-Trihydroxyxanthone, derived from Polygalae Radix, a herbal medicine, stimulates the expression of neurotrophic factors in rat astrocyte primary cultures via cAMP- and ERK-dependent pathways.

1,3,7-Trihydroxyxanthone is a compound isolated from Polygalae Radix, a medicinal herb frequently applied for treatment of psychiatric disordres with symptoms of forgetfulness and depression in ancient China. In current research, this compound was applied onto rat astrocyte primary cultures in exploring the action mechanisms of 1,3,7-trihydroxyxanthone on regulating synthesis of neurotrophic factors. It was found that 1,3,7-trihydroxyxanthone could significantly stimulate the expression of NGF and BDNF in dose-dependent manners: the stimulation was both in mRNA and protein levels. Furthermore, 1,3,7-trihydroxyxanthone might fulfill this effect by regulating critical enzymes, such as plasminogen, tissue plasminogen activator, neuroserpin and tissue inhibitor of metalloproteinases in metabolic pathway of neurotrophic factors. Besides, inhibitors of cAMP- and ERK-dependent pathways, which implied the possible signaling pathway, could reverse this inducing effect. These results might support the potentiality of 1,3,7-trihydroxyxanthone in drug development in treating psychiatric disorders.

A20 prevents obesity-induced development of cardiac dysfunction.

Obesity and an increased free fatty acid (FFA) level are tightly linked, leading to aberrant oxidative stress, inflammation, apoptosis, and progression to cardiovascular disorders. A20 is a ubiquitin-modifying enzyme that plays a significant role in the negative regulation of inflammatory response. Here, we study the role of A20 in obesity-induced heart injury and explore the underlying mechanisms. A20 expression was first increased in mouse hearts after 4 weeks of a high-fat diet (HFD) and then was gradually decreased in the following 20 weeks. Cardiac-specific supplementation with A20 via recombinant adeno-associated virus subtype 9 (rAAV9) could reverse myocardial dysfunction, hypertrophy and fibrosis in mice exposed to 24 weeks of HFD, along with reduced cardiac apoptosis and inflammation. The beneficial actions of A20 were closely associated with its ability to repress TAK1 activation and the downstream inhibition of P38, JNK1/2, and the NF-κB pathway. TAK1 over-expression could efficiently retard the above-mentioned positive effects of A20. Therefore, our data uncovered a novel function of A20 in obesity-induced heart injury and presented a therapeutic approach for the treatment of obesity-related cardiovascular disorders. KEY MESSAGES: A20 expression is downregulated in obesity-related hearts. A20 ameliorates HFD-induced lipid accumulation, ROS, inflammation, apoptosis, hypertrophy, fibrosis, and cardiac dysfunction. A20 represses TAK1 activation and the downstream inhibition of P38, JNK1/2, and the NF-κB pathway. TAK1 overexpression retards the beneficial effects of A20.