NLRP3 inflammasome-a likely target for the treatment of immunologic conjunctivitis: A protocol for systematic review and meta-analysis.

BACKGROUND: Immune-mediated conjunctivitis is a prevalent ocular ailment characterized by inflammation and immune reactions in the conjunctiva. However, the precise causes and therapeutic approaches for this condition remain the main focus for numerous ophthalmological specialists. Recently, accumulating evidence from human and mouse experiments has demonstrated the critical involvement of the NLRP3 inflammasome, IL-1ß, and IL-18 in the development of allergic diseases. Targeting specific NLRP3 inflammasome and its related inhibitors may hold potential as therapeutic agents for immunologic conjunctivitis. Despite this, there has been no systematic review specifically addressing the treatment of immunologic conjunctivitis related to NLRP3. Therefore, this study aims to conduct a systematic review and meta-analysis of currently published randomized controlled trials (RCTs) on NLRP3-related treatments for immunologic conjunctivitis patients, with the goal of evaluating their efficacy and safety. METHODS: We will conduct a comprehensive search for relevant studies on NLRP3 inflammasome inhibitors or NLRP3-related treatments for immunologic conjunctivitis in various databases including PubMed, EMBASE, Cochrane Library, China National Knowledge Infrastructure (CNKI), VIP, and Wanfang. The search will encompass studies from their respective inception dates to July 2023. A meta-analysis will be performed using data extracted from eligible randomized controlled trials (RCTs), focusing on the clinical manifestations of immunologic conjunctivitis, levels of NLRP3-related factors in serum or tear samples, quality of life outcomes, and adverse events. Review Manager 5.4.1 software will be employed for the meta-analysis, and the results will be analyzed using either random-effects or fixed-effects models, depending on the presence of heterogeneity. The reliability and quality of evidence will be evaluated using the Grading of Recommendations, Development, and Evaluation (GRADE) system. RESULTS: The findings of this study will yield robust and high-quality evidence regarding the efficacy and safety of NLRP3-related treatments for immunologic conjunctivitis. This evidence will contribute significantly to our understanding of the potential benefits and risks associated with such treatments and will assist healthcare professionals in making informed decisions regarding the management of immunologic conjunctivitis. CONCLUSION: This study represents the first comprehensive meta-analysis aiming to evaluate the efficacy and safety of NLRP3-related treatments for immunologic conjunctivitis. The findings from this study will provide valuable evidence to guide clinical management strategies for this disease. The results are anticipated to significantly contribute to the understanding of the therapeutic potential and safety profile of NLRP3-related treatments, offering valuable insights for healthcare professionals involved in the care of patients with immunologic conjunctivitis. TRIAL REGISTRATION: Systematic review registration: PROSPERO with registration number CRD42023437076.

Anticancer efficacy of hirsuteine against colorectal cancer by opposite modulation of wild-type and mutant p53.

PURPOSE: The present study aimed to explore the anticancer activity of hirsuteine (HST), an indole alkaloid from the traditional Chinese herbal medicine Uncaria rhynchophylla, against colorectal cancer (CRC) and the underlining mechanism. METHODS: MTT, colony formation, flow cytometry and MDC staining were conducted to confirm the antiproliferative effect of HST on human CRC cells harboring different p53 status. Protein expressions were evaluated by the Western blot analysis. p53 protein half-life and the interaction between p53 and MDM2 were investigated using cycloheximide (CHX)-chase assay and Co-immunoprecipitation (Co-IP), respectively. Transcriptional activity of p53 was examined by qRT-PCR and Chromatin immunoprecipitation (ChIP). Xenograft tumor in nude mice was created to evaluate in vivo anticancer effect of HST against CRC. RESULTS: HST inhibited cell growth, arrested cell cycle and induced autophagy, showing efficient anticancer effects on CRC cells independent of p53 status. In HCT-8 cells, HST prolonged wtp53 half-life, and upregulated mRNA level of p21, suggesting that HST activated the p53 pathway through enhancement of wtp53 stability and transcriptional activity. Meanwhile in SW620 cells, HST induced MDM2-mediated proteasomal degradation of mutp53R273H, increased the DNA-binding ability of mutp53R273H at the p21 promoter, and upregulated mRNA levels of p21 and MDM2, demonstrating the depletion of mutp53R273H and restoration of its wild-type-like properties by HST. p53 knockdown by siRNA significantly impaired the growth inhibition of HST on HCT-8 and SW620 cells. Moreover, HST showed anticancer effects in xenograft tumors, accompanied with an opposite regulation of wtp53 and mutp53 R273H in mechanism. CONCLUSION: This study revealed the anticancer efficacy of HST against CRC via opposite modulation of wtp53 and mutp53 R273H, indicating the potential of HST to be a CRC drug candidate targeting p53 signaling.

Effect of Sutellarin on Neurogenesis in Neonatal Hypoxia-Ischemia Rat Model: Potential Mechanisms of Action.

To investigate the therapeutic efficacy of Scutellarin (SCU) on neurite growth and neurological functional recovery in neonatal hypoxic-ischemic (HI) rats. Primary cortical neurons were cultured to detect the effect of SCU on cell viability of neurons under oxygen-glucose deprivation (OGD). Double immunofluorescence staining of Tuj1 and TUNEL then observed the neurite growth and cell apoptosis in vitro,and double immunofluorescence staining of NEUN and TUNEL was performed to examine the neuronal apoptosis and cell apoptosis in brain tissues after HI in vivo. Pharmacological efficacy of SCU was also evaluated in HI rats by neurobehavioral tests, triphenyl tetrazolium chloride staining, Hematoxylin and eosin staining and Nissl staining. Astrocytes and microglia expression in damaged brain tissues were detected by immunostaining of GFAP and Iba1. A quantitative real-time polymerase chain reaction and western blot were applied to investigate the genetic expression changes and the protein levels of autophagy-related proteins in the injured cortex and hippocampus after HI. We found that SCU administration preserved cell viability, promoted neurite outgrowth and suppressed apoptosis of neurons subjected to OGD both in vitroand in vivo. Meanwhile, 20 mg/kg SCU treatment improved neurological functions and decreased the expression of astrocytes and microglia in the cortex and hippocampus of HI rats. Additionally, SCU treatment depressed the elevated levels of autophagy-related proteins and the p75 neurotrophin receptor (p75NTR) in both cortex and hippocampus. This study demonstrated the potential therapeutic efficacy of SCU by enhancing neurogenesis and restoring long-term neurological dysfunctions, which might be associated with p75NTR depletion in HI rats.

Pectin reduces environmental pollutant-induced obesity in mice through regulating gut microbiota: A case study of p,p'-DDE.

BACKGROUND: The prevalence of obesity has raised global concerns. Environmental pollutants are one of the main causes of obesity. Many studies have demonstrated that dietary fiber could reduce obesity induced by high-fat diets, but whether environmental pollutant-induced obesity can be reversed is still unknown. OBJECTIVES: This study aimed to investigate the effects of pectin on obesity induced by a typical environmental pollutant p,p'-dichlorodiphenyldichloroethylene (p,p'-DDE) and explore the underlying mechanism by which pectin reversed p,p'-DDE-induced obesity. METHODS: p,p'-DDE was used to induce obesity in C57BL/6J mice and pectin was supplied during and after cessation of p,p'-DDE exposure. Body and fat weight gain, plasma lipid profile and insulin resistance of mice were assessed. Gut microbiota composition and the levels of short-chain fatty acids (SCFAs) as well as the receptor proteins and hormones in the SCFAs-related signaling pathway were analyzed. Moreover, p,p'-DDE levels in various tissues of mice were detected. RESULTS: Pectin supplementation reversed body and fat weight gain, dyslipidemia, hyperglycemia and insulin resistance in p,p'-DDE-exposed mice. Furthermore, pectin apparently altered the p,p'-DDE-induced microbial composition and then promoted the levels of SCFAs in colonic feces as well as the expression of G-protein coupled receptors and the concentration of hormone peptide YY (PYY) and glucagon like peptide-1 (GLP-1). Pectin treatment also significantly reduced p,p'-DDE accumulation in mice tissues during p,p'-DDE exposure but did not change p,p'-DDE metabolism after termination of p,p'-DDE exposure. CONCLUSIONS: Pectin had a good effect on reducing p,p'-DDE-induced obesity through regulating gut microbiota and provided a potential strategy for the treatment of environmental pollutant-caused health problems.

The biological activities of prothioconazole enantiomers and their toxicity assessment on aquatic organisms.

Chiral fungicide prothioconazole has a wide range of antifungal spectrum; however, little research has been conducted to evaluate prothioconazole on an enantiomeric level. Five target pathogens and three common aquatic organisms were tested for the enantioselective bioactivity and toxicity of prothioconazole in this work. The antifungal activity of the enantiomers against wheat phytoalexin, rice blast fungus, exserohilum turcicum, Alternaria triticina, and Fusarium avenaceum was determined, and it was found that (-)-prothioconazole were 85 to 2768 times more active than (+)-prothioconazole toward these target organisms. In order to reflect the risk to aquatic ecosystem, the acute toxicity of the enantiomers to Daphnia magna, Chlorella pyrenoidosa, and Lemna minor L. was assessed. It was observed that the toxicity of (-)-prothioconazole to D. magna was 2.2 times higher than (+)-prothioconazole, but it was lower to C. pyrenoidosa and L. minor L. The toxicities of (+)-enantiomer and (-)-enantiomer to D. magna and C. pyrenoidosa were synergy, indicating that the racemate had higher threat to the organisms. It could be concluded that the effects of prothioconazole on target organisms and the acute toxicity to nontarget species were enantioselective with (-)-enantiomer possessing higher efficiency and lower toxicity. Such enantiomeric differences should be taken into consideration when assessing the performance of prothioconazole.

Momordica charantia extracts protect against inhibition of endothelial angiogenesis by advanced glycation endproducts in vitro.

Diabetes mellitus characterized by hyperglycemia favors formation of advanced glycation endproducts (AGEs) capable of triggering vascular complications by interfering with imbalanced inflammation and angiogenesis to eventually impede wound-healing. Momordica charantia (MC, bitter melon) has been shown to prevent AGE formation and to promote angiogenesis in diabetic wounds in animal models. However, the mechanism underlying its effects on angiogenesis is unclear. We investigated the effects of methanolic extracts of MC pulp (MCP), flesh (MCF) and charantin (active component of MC) using an in vitro model of angiogenesis. MC extracts or low concentrations of bovine serum albumin-derived AGEs (BSA-AGEs) stimulated proliferation, migration (using wound-healing assay) and tube formation (using Matrigel™-embedded 3D culture) of bovine aortic endothelial cells (BAEC) together with increases in the phosphorylation of extracellular signal-regulated kinase (ERK)1/2, the key angiogenic signaling cytoplasmic protein. Blocking the receptor for AGEs (RAGE) inhibited low BSA-AGE- and MC extract-induced ERK1/2 phosphorylation and tube formation, indicating the crucial role of RAGE in the pro-angiogenic effects of MC extracts. Moreover, inhibitory effects of high BSA-AGE concentration on cell proliferation and migration were reduced by the addition of MC extracts, which reversed the BSA-AGE anti-angiogenic effect on tube formation. Thus, MC extracts exert direct pro-angiogenic signaling mediated via RAGE to overcome the anti-angiogenic effects of high BSA-AGEs, highlighting the biphasic RAGE-dependent mechanisms involved. This study enhances our understanding of the mechanisms underlying the pro-angiogenic effects of MC extracts in improvement of diabetes-impaired wound-healing.

[Systematic report on re-evaluating kudiezi injection].

There are few articles or reports collecting evidence about Kudiezi injection from premarketing and postmarketing research or studies systematically. This article is an exact miniature of a systematical report about Kudiezi injection. We analyzed information from four aspects, such as quality control reports, non-clinical premarketing safety experiments, postmarketing research (efficacy studies, hospital information system data and national spontaneous reporting system data), and literature analysis. All the four aspects build an evidence body for Kudiezi injection in order to inform its safety use in clinical practice and further study.

A simplified procedure for the determination of organochlorine pesticides and polychlorobiphenyls in edible vegetable oils.

A one-step extraction-purification multiresidue method for the determination of 14 organochlorine pesticides (OCPs) and 7 polychlorinated biphenyls (PCBs) in edible vegetable oils based on matrix solid-phase dispersion (MSPD) has been developed. The experimental parameters affecting the recoveries and the efficiency of the cleanup procedure were thoroughly evaluated. Under an optimised condition, 0.5 g of oil sample was blended with 3.5 g of sulfuric acid-impregnated silica and 0.8 g of silica gel was used as co-column absorbent. The PCBs and OCPs were eluted by 10 mL of n-hexane/dichloromethane (70:30, v/v) and determined by gas chromatography equipped with an electron capture detector (GC-ECD). Good recoveries were obtained in the range of 69.6-105.3% with relative standard deviations (RSD) values below 15% in most cases. The limits of detection (LOD), based on a signal-to-noise ratio (S/N) of 3, were in the range of 0.04-0.74 ng/g.

Characterization of phloroglucinol derivatives and diterpenes in Euphorbia ebracteolata Hayata by utilizing ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry.

Euphorbia ebracteolata Hayata (E. ebracteolata) is a Chinese herbal medicine used for the treatment of tumor diseases. An ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS) based chemical profiling approach was established for the rapid separation and characterization on phloroglucinol derivatives and diterpenes in E. ebracteolata. Three phloroglucinol derivatives and nine diterpenes were identified by exact mass measurement and were further confirmed by Ms2 data. In addition, the chemical profiles of six compounds were acquired by reference standards. Furthermore, the fragmentation rules of phloroglucinol derivatives and diterpenes of E. ebracteolata were analyzed, and each chromatographic peak was classified.

Muscone exerts neuroprotection in an experimental model of stroke via inhibition of the fas pathway.

Identifying small molecules that are neuroprotective against stroke injury will be highly beneficial for treatment therapies. A cell viability assay and gas chromatography-mass spectrometry were used to identify active small molecules in XingNaoJing, which is a well known Chinese medicine prescribed for the effective treatment of stroke. Studies have found that muscone is the active compound that prevents PC12 cell and cortical neuron damage following various injuries. Analysis of apoptosis indicated that muscone inhibited glutamate-induced apoptotic cell death of PC12 cells and cortical neurons. Fas and caspase-8 expression were upregulated following glutamate treatment in cortical neurons, and was markedly attenuated in the presence of muscone. Furthermore, muscone significantly reduced cerebral infarct volume, neurological dysfunction and inhibited cortical neuron apoptosis in middle cerebral artery occluded (MCAO) rats in a dose-dependent manner. Moreover, a significant decrease in Fas and caspase-8 expression in the rat cortex was observed in MCAO rats treated with muscone. Our results demonstrate that muscone may be a small active molecule with neuroprotective properties, and that inhibition of apoptosis and Fas is an important mechanism of neuroprotection by muscone. These findings suggest a potential therapeutic role for muscone in the treatment of stroke.

Targeting of the Sonic Hedgehog pathway by atractylenolides promotes chondrogenic differentiation of mesenchymal stem cells.

Molecules that enhance chondrogenic differentiation in mesenchymal stem cells (MSCs) were identified and isolated using an in vitro Gli reporter gene assay in MSCs incorporating a Sonic Hedgehog (Shh) target. Atractylenolide III, which promoted Gli1-mediated transcriptional activity, was isolated from an ethyl acetate extract of the Rhizoma, Atractylodis macrocephalae. After dehydration, atractylenolide III was transformed to atractylenolide I. Both atractylenolides were confirmed by MS, UV, IR, 1H- and 13C-NMR spectra. Atractylenolide III (which contains -OH at the 8-position) and atractylenolide I (which lacks -OH at the 8-position) were found to effectively promote the activity of the Gli promoter. While the hydroxyl group of atractylenolide III was not essential for the effect of atractylenolide, its effect was dependent on Shh signaling. Phenotypic cellular analysis indicated that atractylenolides induced MSCs to differentiate into chondrocytes, as shown by increased expression of specific chondrogenic markers including collagen II, aggrecan and the cartilage related transcription factor, Sox9. Atractylenolides significantly increased the expression of Shh and its target gene Gli-1, indicating that Shh signaling was activated by atractylenolides. Moreover, inhibition of Shh signaling reduced the effect of atractylenolides on the chondrogenic phenotype. The discovery that atractylenolides induce chondrocytes from MSCs is promising for bony disease therapy.

[Development of acupuncture in Guinea].

Guinea is the first country who established diplomatic relations with P. R. China in sub-Saharan Africa. China and Guinea have maintained good relationship for the past years. Chinese Ministry of Health has sent twenty-one medical teams to Guinea since 1968. This article describes the development of acupuncture in Guinea. Based on the status of acupuncture in the Hospital Ignace Deen, in which the author had worked, the general situation, the current problems, and the development trends of acupuncture treatment in Guinea are introduced. The problems and future development trends of acupuncture in Guinea are discussed.

Molecular cloning and characterization of Crmdr1, a novel MDR-type ABC transporter gene from Catharanthus roseus.

A novel gene encoding a MDR-like ABC transporter protein was cloned from Catharanthus roseus, a medicinal plant with more than 120 kinds of secondary metabolites, through rapid amplification of cDNA ends (RACE). This gene (named as Crmdr1; GenBank accession no.: DQ660356) had a total length of 4395 bp with an open reading frame of 3801 bp, and encoded a predicted polypeptide of 1266 amino acids with a molecular weight of 137.1 kDa. The CrMDR1 protein shared 59.8, 62.5, 60.0 and 58.2% identity with other MDR proteins isolated from Arabidopsis thaliana (AAD31576), Coptis japonica (CjMDR), Gossypium hirsutum (GhMDR) and Triticum aestivum (TaMDR) at amino acid level, respectively. Southern blot analysis showed that Crmdr1 was a low-copy gene. Expression pattern analysis revealed that Crmdr1 constitutively expressed in the root, stem and leaf, but with lower expression in leaf. The domains analysis showed that CrMDR1 protein possessed two transmembrane domains (TMDs) and two nucleotide binding domains (NBDs) arranging in "TMD1-NBD1-TMD2-NBD2" direction, which is consistent with other MDR transporters. Within NBDs three characteristic motifs common to all ABC transporters, "Walker A", "Walker B" and C motif, were found. These results indicate that CrMDR1 is a MDR-like ABC transporter protein that may be involved in the transport and accumulation of secondary metabolites.

[HPLC fingerprint of Danggui Buxue decoction].

OBJECTIVE: To establish the fingerprint of soup of Danggui Buxue decoction. METHODS: HPLC with Nucleodur C18 Gravity colum was used and the Acetonitrile-water (gradient elution) as a mobile phase and detecting wavelength at 203 nm. RESULTS: There were 15 main peaks in the soup of Danggui Buxue decoction. 15 come from Radix astragali and 7 come from Radix angelicae sinensis. CONCLUSION: This fingerprint can be used as a reference for stablility of soup of Danggui Buxue decoction.

Direct enantiomeric resolutions of chiral triazole pesticides by high-performance liquid chromatography.

Cellulose-tris (3,5-dimethylphenylcarbamate; CDMPC) was synthesized and coated on aminopropylsilica to prepare chiral stationary phase (CSP). Normal-phase high-performance liquid chromatography (HPLC) methods for the resolutions of five chiral triazole pesticides, diniconazole, tebuconazole, hexaconazole, triadimefon and flutriafol, on the CSP were developed. Several operating parameters such as mobile phase composition, modifier and column temperature were studied for the optimization of the resolutions. Better separations were achieved using 2% iso-butanol for diniconazole, 2% ethanol for tebuconazole, 2% iso-propanol for hexaconazole, 1% n-butanol for triadimefon and 2% n-propanol for flutriafol as modifiers in n-hexane at 0 degrees C with the resolution factors (Rs) of 1.62, 1.66, 2.46, 1.68 and 1.98, respectively. Low temperature was better for the resolutions. Validation of the methods included linearity and precision.

[Study on GC-MS fingerprint analysis in rhizome of volatile oil of Acorus tatarinowii].

OBJECTIVE: To establish the method of fingerprint analysis on volatile oil in rhizome of Acorus tatarinowii by GC-MS, and to study the main characteristic components. METHOD: The main components of 10 samples were determined by GC-MS. RESULT: The injector temperature was 250 degrees C. The interface temperature was 230 degrees C. The column flow was 1.3 mL x min(-1). The column pressure was 80 kPa. The detector volt was 1.4 kV. The temperature rate was 3 degrees C x min(-1). And the main characteristic components were composed of the methyleugenol (2.13%), cis-methylisoeugenol (4.48%), trans-methylisoeugenol (0.82%), gamma-asarone (4.51%), beta-asarone (66.15%), alpha-asarone (6.35%). And the RSD of precision and reproducibility and stability was almost in the range of 5%. CONCLUSION: The method is reliable, accurate and can be used for fingerprint analysis of volatile oil of Acorus tatarinowii.