Hyperinsulinemia impairs decidualization via AKT-NR4A1 signaling: new insight into polycystic ovary syndrome (PCOS)-related infertility.

BACKGROUND: Investigating the underlying molecular mechanisms responsible for endometrial dysfunction in women with PCOS is essential, particularly focusing on the role of hyperinsulinemia. METHODS: We explored the role of insulin in the decidualization process using a synthetic decidualization assay. To dissect the effects of PI3K/AKT-NR4A signaling, we employed small interfering RNAs (siRNAs) targeting the NR4A genes and inhibitors of the PI3K/AKT pathway. We also investigated the disruption of AKT-NR4A1 signaling in the endometrium of PCOS female rats induced with dehydroepiandrosterone (DHEA). Quantitative real-time PCR (qRT-PCR) and Western blot (WB) analyses were utilized to evaluate gene expression regulation. RESULTS: Insulin was found to suppress the expression of decidualization markers in human endometrial stromal cells (hESC) in a dose-dependent manner, concurrently triggering an inappropriate activation of the PI3K/AKT pathway. Members of the NR4A family, as downstream effectors in the PI3K/AKT pathway, were implicated in the insulin-induced disruptions during the decidualization process. Moreover, the endometrium of PCOS models showed significantly elevated levels of phosphorylated (Ser473) AKT, with a corresponding reduction in Nr4a1 protein. CONCLUSIONS: Our research demonstrates that insulin negatively regulates decidualization in hESC via the PI3K/AKT-NR4A pathway. In vivo analysis revealed a significant dysregulation of the AKT-NR4A1 pathway in the endometrium of PCOS rats. These findings offer novel insights into the pathogenesis of infertility and endometrial disorders associated with hyperinsulinemia in PCOS.

Serine/threonine kinase 36 induced epithelial-mesenchymal transition promotes docetaxel resistance in prostate cancer.

To investigate the role and potential mechanism of serine/threonine kinase 36 (STK36) in docetaxel resistance-prostate cancer (PCa). The expression of STK36 in PCa and the correlation with clinicopathological characteristics of PCa patients were analyzed using the data from different databases and tissue microarrays. To investigate the role of STK36 on cell proliferation, invasion, and migration, STK36 was overexpressed and silenced in DU-145 and PC-3 cell lines. Cell counting kit-8 (CCK8) was used to test cell proliferation. Cell invasion and migration were detected by cell wound scratch assay and trans well, respectively. The expression profile of STK36, E-Cadherin, and Vimentin was analyzed by Western blot. Cell apoptosis was detected by the TUNEL assay. STK36 expression was upregulated in PCa tissue compared with adjacent benign PCa tissue; it was higher in patients with advanced stages compared with lower stages and was significantly correlated with decreased overall survival. Up-regulation of STK36 significantly promoted the proliferation, invasion, and migration of DU-145 and PC-3 cells and compensated for the suppression caused by docetaxel treatment in vitro. A striking apoptosis inhibition could be observed when dealing with docetaxel, although the apoptosis of DU-145 and PC-3 cells was not affected by the STK36 exclusive overexpression. Besides, E-Cadherin expression was restrained while the expression levels of vimentin were all enhanced. The knockdown of STK36 reversed the above process. STK36 up-regulation could accelerate the biological behavior and docetaxel resistance of PCa by epithelial-mesenchymal transition (EMT) activation. STK36 may be potentially used as a target in PCa resolvent with docetaxel.

Caspar negatively regulates anti-bacterial immunity by controlling the nuclear translocation of Relish in Chinese mitten crab (Eriocheir sinensis).

Caspar, a homolog of the Fas-associated factor 1 (FAF1) family, contains an N-terminal ubiquitin interaction domain, a ubiquitin-like self-association domain, and a C-terminal ubiquitin regulatory domain. Caspar has been reported to be involved in the antibacterial immunity of Drosophila, which is unclear whether it is involved in the antibacterial immune process of crustaceans. In this article, we identified a Caspar gene in Eriocheir sinensis and named it EsCaspar. EsCaspar positively respond to bacterial stimulation and downregulate the expression of certain associated antimicrobial peptides by inhibiting the nuclear translocation of EsRelish. Thus, EsCaspar might be a suppressor of the immune deficiency (IMD) pathway that prevents over-activation of the immune system. Indeed, excess EsCaspar protein in crabs reduced resistance to bacterial infection. In conclusion, EsCaspar is a suppressor of the IMD pathway in crabs that plays a negative regulatory role in antimicrobial immunity.

Preparation and preliminary evaluation of SARS-CoV-2 DNA vaccine based on PLGA nanoparticles / 药学学报

We constructed and optimized the plasmid DNA (pDNA) Opt-S encoding the gene of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S) protein, using poly (lactic-co-glycolic acid) copolymer (PLGA) as a delivery carrier for pDNA. PLGA-pDNA NPs were loaded by nanoprecipitation and its properties in vitro were preliminary evaluated. The results showed that the prepared PLGA-pDNA NPs were regular morphology, clear edges, with an average particle size of (184.2 ± 2.4) nm, polydisperse index (PDI) of 0.093 ± 0.013, zeta potential of (-68.10 ± 0.36) mV, and encapsulation rate of (98.92 ± 0.22)%. The PLGA-pDNA NPs were stable at -20 ℃ for 7 months and could protect pDNA against nuclease degradation. And they also exhibited sustained release of pDNA in vitro. The PLGA-pDNA NPs have low cytotoxicity and high safety. In addition, in vitro transfection experiments showed that the SARS-CoV-2 S gene could enter cells and be expressed. These results indicate that PLGA-pDNA NPs non-viral gene vector have simple preparation process and good performance, which are expected to provide a new idea for the research and development of SARS-CoV-2 vaccine.

Research advances of adipose stem cell matrix gel in promoting wound healing / 中华烧伤杂志

In recent years, with the problem of aging population in China being prominant, the number of patients with chronic wounds such as diabetic foot, pressure ulcer, and vascular ulcer is increasing. Those diseases seriously affect the life quality of patients and increase the economy and care burden of the patients' family, which have been one of the most urgent clinical problems. Many researches have confirmed that adipose stem cells can effectively promote wound healing, while exogenous protease is needed, and there are ethical and many other problems, which limit the clinical application of adipose stem cells. Adipose stem cell matrix gel is a gel-like mixture of biologically active extracellular matrix and stromal vascular fragment obtained from adipose tissue by the principle of fluid whirlpool and flocculation precipitation. It contains rich adipose stem cells, hematopoietic stem cells, endothelial progenitor cells, and macrophages, etc. The preparation method of adipose stem cell matrix gel is simple and the preparation time is short, which is convenient for clinical application. Many studies at home and abroad showed that adipose stem cell matrix gel can effectively promote wound healing by regulating inflammatory reaction, promoting microvascular reconstruction and collagen synthesis. Therefore, this paper summarized the preparation of adipose stem cell matrix gel, the mechanism and problems of the matrix gel in promoting wound repair, in order to provide new methods and ideas for the treatment of chronic refractory wounds in clinic.

Influencing factors of corneal epithelial punctate staining in patients wearing orthokeratology / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To investigate the influencing factors of punctate staining of corneal epithelium in patients wearing orthokeratology.METHOD: Data of 280 cases wearing orthokeratology were collected, including 185 cases in the group without corneal staining and 95 cases in the group with corneal staining. All patients were examined for general distant vision, intraocular pressure, slit lamp, fundus examination after mydriasis, comprehensive optometry, corneal topography, corneal thickness, corneal endothelium, axial length, Schirmer Ⅰtest(SⅠt)before wearing lenses, meibomian gland loss score before wearing lenses, eccentric distance, interleukin-2(IL-2)in tear, tumor necrosis factor-α(TNF-α)content analysis and so on. The influencing factors of corneal epithelium punctate staining were analyzed by univariate and multivariate Logistic regression.RESULTS: There were significant differences in preoperative diopter, preoperative meibomian gland deletion score, IL-2, TNF-α and lens sediment between the two groups(all P<0.05). Logistic regression analysis showed that diopter before wearing lenses was a protective factor for corneal epithelium punctate staining. Before wearing lenses, the loss of meibomian gland score, IL-2, TNF-α and lens deposits were the risk factors of corneal epithelium punctate staining. In the detection of corneal epithelium punctate staining, the comprehensive advantage of lens deposits was obvious, the specificity of lens deposits was higher, and the sensitivity of IL-2 was the highest. CONCLUSIONS: Before wearing lenses, diopter is the protective factor of corneal epithelium punctate staining, and the loss of meibomian gland score, IL-2, TNF-α and lens deposits are the risk factors of corneal epithelium punctate staining.

Oligodendrocytes and myelin: Active players in neurodegenerative brains?

Oligodendrocytes (OLs) are a major type of glial cells in the central nervous system that generate multiple myelin sheaths to wrap axons. Myelin ensures fast and efficient propagation of action potentials along axons and supports neurons with nourishment. The decay of OLs and myelin has been implicated in age-related neurodegenerative diseases and these changes are generally considered as an inevitable result of neuron loss and axon degeneration. Noticeably, OLs and myelin undergo dynamic changes in healthy adult brains, that is, newly formed OLs are continuously added throughout life from the differentiation of oligodendrocyte precursor cells (OPCs) and the pre-existing myelin sheaths may undergo degeneration or remodeling. Increasing evidence has shown that changes in OLs and myelin are present in the early stages of neurodegenerative diseases, and even prior to significant neuronal loss and functional deficits. More importantly, oligodendroglia-specific manipulation, by either deletion of the disease gene or enhancement of myelin renewal, can alleviate functional impairments in neurodegenerative animal models. These findings underscore the possibility that OLs and myelin are not passively but actively involved in neurodegenerative diseases and may play an important role in modulating neuronal function and survival. In this review, we summarize recent work characterizing by OLs and myelin changes in both healthy and neurodegenerative brains and discuss the potential of targeting oligodendroglial cells in treating neurodegenerative diseases.

Research progress of exosomes based targeted delivery of antitumor drugs / 药学学报

Exosomes are one of the most important ways of cell-to-cell communication in living lives. They are involved in major physiological and pathological processes, including drug resistance, infection propagation, cancer development and cardiovascular diseases. The biological functions of exosomes made it possess characteristics of low immunogenicity, high delivery efficiency, ability to cross multiple biological barriers and targeting capacity, which also encourage people to try to use it as a drug carrier to overcome the disadvantages of poor stability, low solubility, low bioavailability and high toxicity of some drugs. In this paper, the latest progress of exosomes in the delivery of antitumor drugs, including small chemotherapeutic drugs, biological macromolecules and nucleic acid drugs, is reviewed. In addition, the isolation, drug loading, and modification method and the application prospect of exosomes are also discussed.

Mechanism of intestinal flora in process of knee osteoarthritis in mice alleviated by Jiawei Duhuo Jisheng Mixture / 中国药理学通报

Aim To investigate the potential mechanism of Jiawei Duhuo Jisheng Mixture regulating intestinal flora in the treatment of knee osteoarthritis(KOA)by 16S rRNA sequencing.Methods Eight-week-old male C57 mice were randomly divided into three groups:sham group,DMM group,and model+Jiawei Duhuo Jisheng Mixture group(Mixture group),6 mice per group.KOA model was induced by destabilization of medial meniscus surgery.16.25 mL·kg-1 dose mixture was given daily to the mixture group,and normal saline was given to the sham and DMM group.After eight weeks,the knee joints and colons of mice were collected,and the knee joints were prepared into paraffin sections,and the cartilage changes were observed with Safranin O-Fast Green and immunohistochemistry staining.16S rRNA sequencing of intestinal contents was performed to observe the changes of intestinal flora.Results Compared with model group,Jiawei Duhuo Jisheng Mixture could significantly reduce cartilage wear and OARSI score(P=0.033 5,P=0.029 5).16S rRNA sequencing showed that Jiawei Duhuo Jisheng Mixtrue could change the intestinal flora richness of KOA model mice,and improve the Alpha diversity(Chao1,Simpson)and Beta diversity(PCoA,NMDS).LefSe analysis showed that there were species with significant difference in abundance among the three groups(P=0.001),mainly including Lactobacillus,Firmicutes,Proteobacteria and other species.MetaCyc analysis indicated that Jiawei Duhuo Jisheng Mixture had effects on various metabolic pathways such as fatty acid,sugar and amino acid of intestinal flora(P<0.05).Conclusions Jiawei Duhuo Jisheng Mixtrue can effectively protect the articular cartilage and delay the progression of KOA.The mechanism may be through regulating the intestinal flora structure,protecting the intestinal barrier and reducing the inflammatory response.

The Disorders of Endometrial Receptivity in PCOS and Its Mechanisms.

Polycystic ovary syndrome (PCOS) is a mysterious and complicated endocrine disease with the combination of metabolic, reproductive, psychological dysfunctions. Impaired endometrial receptivity and ovulation disorders/anovulation are both important causes of PCOS-related infertility. However, change in endometrium has never received the same attention as ovulatory dysfunction. Besides, putting emphasis on endometrial function may be more realistic for PCOS-related infertility, given the wide use of assisted reproductive technology. The present review focuses on the disorders of endometrial receptivity of patients with PCOS, summarizes the changes of the indicators of endometrial receptivity including leukemia inhibitory factor, homeobox genes A, pinopodes, αvß3-integrin, and intercellular junctions and also analyzes the possible mechanisms of decreased endometrial receptivity and its relationship with the main endocrine and metabolic disorders of PCOS such as hyperandrogenism, inflammation, insulin resistance, and obesity. Despite several biomarkers have been found to be associated with decreased endometrial receptivity in PCOS, the clinical relevance of these findings still awaits future clarification.

The Complicated Effects of Extracellular Vesicles and Their Cargos on Embryo Implantation.

As a rate-limiting step in pregnancy, embryo implantation is highly dependent on intercellular communication. Extracellular vesicles (EVs) are newly identified to be important in the course of intercellular communication. EVs have been isolated from a wide variety of biofluids and tissues, including plasma, liver, uterine, semen, embryo, etc. The present and future use of EVs not only as biomarkers, but also as targeting drug delivery system, is promisingly pave the way for advanced comprehension of implantation failure in reproductive diseases. However, as the precise mechanisms of EVs in embryo implantation has not been elucidated yet. Herein, we summarize the current knowledge on the diverse effects of EVs from various sources and their cargos such as microRNA, long non-coding RNA, protein, etc. on embryo implantation, and the potential mechanisms of EVs in reproductive diseases such as recurrent implantation failure, polycystic ovary syndrome and endometriosis. It is essential to note that many of the biologically plausible functions of EVs in embryo implantation discussed in present literatures still need further research in vivo.

Main Chemical Constituents and Modern Pharmacological Action of Schisandrae Chinensis Fructus： A Review / 中国实验方剂学杂志

Schisandrae Chinensis Fructus （SCF）， a commonly used clinical Chinese medicine， is rich in chemical components， including lignans， volatile oils， polysaccharides， organic acids， terpenoids， and flavonoids. It has a high medicinal value， which is manifested in the treatment of palpitation， insomnia， spontaneous perspiration， internal heat， consumptive thirst， fluid injury， chronic cough， asthma， frequent urination， enuresis， nocturnal emission， chronic diarrhea， etc. Modern pharmacological studies have found that SCF has sedative， hypnotic， brain invigorating， analgesic， anticonvulsant， and antidepressant effects in the central nervous system. In the digestive system， it can regulate gastrointestinal motility and protect the liver. In the immune system， it is effective in resisting tumors and human immunodeficiency virus （HIV）， and also potent in protecting the cardiovascular system， lung and kidney， reducing blood sugar， promoting reproduction， inhibiting bacteria， resisting hyperprolactinemia and osteoporosis， and protecting against embryo damage and retina injury. This study reviewed the available research on clinical pharmacological effects of SCF in recent years and provided ideas for further research on SCF and theoretical basis for its rational development and utilization， which was of great guiding significance in clinical disease treatment.

Fully Integrated, Simple, and Low-Cost Electrochemical Sensor Array for in Situ Water Quality Monitoring.

Rapid, accurate and inexpensive monitoring of water quality parameters is indispensable for continued water safety, especially in resource-limited areas. Most conventional sensing systems either can only monitor one parameter at a time or lack user-friendly on-site monitoring capabilities. A fully integrated electrochemical sensor array is an excellent solution to this barrier. Electrochemical sensing methods involve transduction of water quality parameters where chemical interactions are converted to electrical signals. The challenge remains in designing low-cost, easy-to-use, and highly sensitive sensor array that can continuously monitor major water quality parameters such as pH, free chlorine, temperature along with emerging pharmaceutical contaminants, and heavy metal without the use of expensive laboratory-based techniques and trained personnel. Here, we overcame this challenge through realizing a fully integrated electrochemical sensing system that offers simultaneous monitoring of pH (57.5 mV/pH), free chlorine (186 nA/ppm), and temperature (16.9 mV/°C) and on-demand monitoring of acetaminophen and 17ß-estradiol (<10 nM) and heavy metal (<10 ppb), bridging the technological gap between signal transduction, processing, wireless transmission, and smartphone interfacing. This was achieved by merging nanomaterials and carbon nanotube-based sensors fabricated on microscopic glass slides controlled by a custom-designed readout circuit, a potentiostat, and an Android app. The sensing system can be easily modified and programmed to integrate other sensors, a capability that can be exploited to monitor a range of water quality parameters. We demonstrate the integrated system for monitoring tap, swimming pool, and lake water. This system opens the possibility for a wide range of low-cost and ubiquitous environmental monitoring applications.

The myodural bridge complex defined as a new functional structure.

PURPOSE: The connective tissue between suboccipital muscles and the cervical spinal dura mater (SDM) is known as the myodural bridge (MDB). However, the adjacent relationship of the different connective tissue fibers that form the MDB remains unclear. This information will be highly useful in exploring the function of the MDB. METHODS: The adjacent relationship of different connective tissue fibers of MDB was demonstrated based upon three-dimensional visualization model, P45 plastinated slices and histological sections of human MDB. RESULTS: We found that the MDB originating from the rectus capitis posterior minor muscle (RCPmi), rectus capitis posterior major muscle (RCPma) and obliquus capitis inferior muscle (OCI) in the suboccipital region coexists. Part of the MDB fibers originate from the ventral aspect of the RCPmi and, together with that from the cranial segment of the RCPma, pass through the posterior atlanto-occipital interspace (PAOiS) and enter into the posterior aspect of the upper cervical SDM. Also, part of the MDB fibers originate from the dorsal aspect of the RCPmi, the ventral aspect of the caudal segment of the RCPma, and the ventral aspect of the medial segment of the OCI, enter the central part of the posterior atlanto-axial interspace (PAAiS) and fuse with the vertebral dura ligament (VDL), which connects with the cervical SDM. CONCLUSIONS: Our findings prove that the MDB exists as a complex structure which we termed the 'myodural bridge complex' (MDBC). In the process of head movement, tensile forces could be transferred possibly and effectively by means of the MDBC. The concept of MDBC will be beneficial in the overall exploration of the function of the MDB.

Paraherquamide J, a new prenylated indole alkaloid from the marine-derived fungus Penicillium janthinellum HK1-6.

A new prenylated indole alkaloid, named paraherquamide J (1), together with four known compounds (2-5), were isolated from the mangrove rhizosphere soil-derived fungus Penicillium janthinellum HK1-6. The planar structure and relative configuration of 1 were determined by detailed analysis of the spectroscopic data especially the NOESY spectrum. The absolute configuration of 1 was determined by ECD spectra. Compound 2 was first isolated as a natural product and named as paraherquamide K. All isolated metabolites were evaluated for their antibacterial, topoisomerase I (topo I) inhibitory activities and lethality towards brine shrimp Artemia salina.

Survivin Promotes Piperlongumine Resistance in Ovarian Cancer.

Ovarian cancer is one of the most fatal female malignancies while targeting apoptosis is critical for improving ovarian cancer patients' lives. Survivin is regarded as the most robust anti-apoptosis protein, and its overexpression in ovarian cancer is related to poor survival and apoptosis resistance. Piperlongumine (PL) extracted from peppers is defined as an active alkaloid/amide and exhibits a broad spectrum of antitumor effects. Here, we demonstrate that PL induces the rapid depletion of survivin protein levels via reactive oxygen species (ROS)-mediated proteasome-dependent pathway in vitro, while exerting a remarkable inhibitory influence on the proliferation of ovarian cancer cells. Overexpression of survivin raises the survival rate of ovarian cancer cells to PL. Moreover, PL inhibits ovarian cancer cells xenograft tumor growth and downregulates survivin in vivo. Our findings reveal a previously unrecognized mechanism of PL in suppressing survivin expression as well as survivin promotes piperlongumine resistance in ovarian cancer and suggest that ROS-mediated proteasome-dependent pathway can be exploited to overcome apoptosis resistance triggered by aberrant expression of survivin.

Two new unsaturated fatty acids from the mangrove rhizosphere soil-derived fungus Penicillium javanicum HK1-22.

Two new unsaturated fatty acids, 6R,8R-dihydroxy-9Z,12Z-octadecadienoic acid (1) and methyl-6R,8R-dihydroxy-9Z,12Z-octadecadienoate (2), and two known 9Z,12Z-octadecadienoic acid analogues (3, 4) together with a known sesquiterpenoid (5) were isolated from the mangrove rhizosphere soil-derived fungus Penicillium javanicum HK1-22. An acetonide derivative (1a) from 1 was also prepared. The relative configuration of 1 was determined by analysis of the 1D and 2D NOE spectra of 1a. The absolute configuration of 1 was assigned on the basis of biogenetic considerations. The antifungal activity of the high yield compound 5 was evaluated against four strains of crop pathogens and it showed significant antifungal activities against all the tested strains.

MK-801 attenuates lesion expansion following acute brain injury in rats: a meta-analysis.

OBJECTIVE: To evaluate the efficacy and safety of MK-801 and its effect on lesion volume in rat models of acute brain injury. DATA SOURCES: Key terms were "stroke", "brain diseases", "brain injuries", "brain hemorrhage, traumatic", "acute brain injury", "dizocilpine maleate", "dizocilpine", "MK-801", "MK801", "rat", "rats", "rattus" and "murine". PubMed, Cochrane library, EMBASE, the China National Knowledge Infrastructure, WanFang database, the VIP Journal Integration Platform (VJIP) and SinoMed databases were searched from their inception dates to March 2018. DATA SELECTION: Studies were selected if they reported the effects of MK-801 in experimental acute brain injury. Two investigators independently conducted literature screening, data extraction, and methodological quality assessments. OUTCOME MEASURES: The primary outcomes included lesion volume and brain edema. The secondary outcomes included behavioral assessments with the Bederson neurological grading system and the water maze test 24 hours after brain injury. RESULTS: A total of 52 studies with 2530 samples were included in the systematic review. Seventeen of these studies had a high methodological quality. Overall, the lesion volume (34 studies, n = 966, MD = -58.31, 95% CI: -66.55 to -50.07; P < 0.00001) and degree of cerebral edema (5 studies, n = 75, MD = -1.21, 95% CI: -1.50 to -0.91; P < 0.00001) were significantly decreased in the MK-801 group compared with the control group. MK-801 improved spatial cognition assessed with the water maze test (2 studies, n = 60, MD = -10.88, 95% CI: -20.75 to -1.00; P = 0.03) and neurological function 24 hours after brain injury (11 studies, n = 335, MD = -1.04, 95% CI: -1.47 to -0.60; P < 0.00001). Subgroup analysis suggested an association of reduction in lesion volume with various injury models (34 studies, n = 966, MD = -58.31, 95% CI: -66.55 to -50.07; P = 0.004). Further network analysis showed that 0-1 mg/kg MK-801 may be the optimal dose for treatment in the middle cerebral artery occlusion animal model. CONCLUSION: MK-801 effectively reduces brain lesion volume and the degree of cerebral edema in rat models of experimental acute brain injury, providing a good neuroprotective effect. Additionally, MK-801 has a good safety profile, and its mechanism of action is well known. Thus, MK-801 may be suitable for future clinical trials and applications.

New Naphtho-γ-Pyrones Isolated from Marine-Derived Fungus Penicillium sp. HK1-22 and Their Antimicrobial Activities.

Three novel monomeric naphtho-γ-pyrones, peninaphones A-C (compounds 1-3), along with two known bis-naphtho-γ-pyrones (compounds 4 and 5) were isolated from mangrove rhizosphere soil-derived fungus Penicillium sp. HK1-22. The absolute configurations of compounds 1 and 2 were determined by electronic circular dichroism (ECD) spectra, and the structure of compound 3 was confirmed by single-crystal X-ray diffraction analysis. Compounds 4 and 5 are a pair of hindered rotation isomers. A hypothetical biosynthetic pathway for the isolated monomeric and dimeric naphtho-γ-pyrones is also discussed in this study. Compounds 1-3 showed antibacterial activity against Staphylococcus aureus (ATCC 43300, 33591, 29213, and 25923) with minimum inhibitory concentration (MIC) values in the range of 12.5-50 µg/mL. Compound 3 exhibited significant activity against the rice sheath blight pathogen Rhizoctonia solani.

Riluzole promotes neurological function recovery and inhibits damage extension in rats following spinal cord injury: a meta-analysis and systematic review.

Spinal cord injury (SCI) is a devastating condition that has few treatment options. Riluzole, a sodium channel blocker used to treat amyotrophic lateral sclerosis, has been initially trialed in human SCI. We performed a systematic review to critically assess the efficacy of riluzole in locomotor recovery and damage extension in SCI rat models, and the potential for clinical translation. PubMed, Embase, Cochrane Library, and Chinese databases were searched from their inception date to March 2018. Two reviewers independently selected animal studies that evaluated neurological recovery and lesion area following riluzole treatment in SCI rat models, extracted data and assessed methodological quality. Pairwise meta-analysis, subgroup analysis, and network meta-analysis were performed to assess the effects of riluzole on SCI. Ten eligible studies were included. Two studies had high methodological quality. Overall, the Basso, Beattie, and Bresnahan scores were increased in riluzole-treated animals versus controls, and effect sizes showed a gradual increase from the 1st (five studies, n = 104, mean difference = 1.24, 95% CI = 0.11 to 2.37, p = 0.03) to 6th week after treatment (five studies, n = 120, mean difference = 2.34, 95% CI = 1.26 to 3.42, p < 0.0001). Riluzole was associated with improved outcomes in the inclined plane test and the tissue preservation area. Subgroup analyses suggested an association of locomotor recovery with riluzole dose. Network meta-analysis showed that 5 mg/kg riluzole exhibited greater protection than 2.5 and 8 mg/kg riluzole. Collectively, this review suggests that riluzole has a protective effect on SCI, with good safety and a clear mechanism of action and may be suitable for future clinical trials or applications. However, animal results should be interpreted with caution given the known limitations in animal experimental design and methodological quality.