The Influence of CD40/CD40L, MMP2/MMP9 on Uterine Artery Blood Flow and Their Expression in Recurrent Miscarriage.

Objective: This study aims to investigate the expression levels of soluble CD40L (sCD40L), matrix metalloproteinase 2 (MMP2), and matrix metalloproteinase 9 (MMP9) in the serum of patients experiencing recurrent abortion and their impact on uterine artery blood flow. Methods: A cohort of 200 patients with recurrent abortion was selected for this investigation. The levels of sCD40L, MMP2, and MMP9 in serum were assessed using ELISA, while ultrasound was employed to measure the pulsatility index (PI) and resistance index (RI) in uterine artery blood flow. Pregnancy outcomes were observed, and the expression of CD40/CD40L and MMP2/MMP9 in villi tissues was compared between patients experiencing recurrent abortion failure and those with normal pregnancies. Results: In the successful pregnancy group of patients with recurrent spontaneous abortion (RSA), serum levels of sCD40L, MMP2, and MMP9 were significantly lower than those in the failed pregnancy group. Additionally, both RI and PI were notably reduced. The expression of each gene showed a correlation with RI and PI. Furthermore, the expression levels of CD40, CD40L, MMP2, and MMP9 in the pregnancy failure group were significantly higher than in the normal voluntary termination group. Conclusion: Serum levels of sCD40L, MMP2, and MMP9, along with non-invasive and easily accessible indicators such as PI and RI in uterine artery blood flow measured by ultrasound, emerge as potential predictive markers for the outcome of recurrent miscarriage pregnancies. Moreover, these indicators can serve as valuable evaluation markers in clinical practice, facilitating the monitoring of treatment effectiveness for recurrent miscarriage.

Lasiokaurin Regulates PLK1 to Induce Breast Cancer Cell G2/M Phase Block and Apoptosis.

Aim of the study: To investigate the anti-tumor effects of Lasiokaurin on breast cancer and explore its underlying molecular mechanism. Materials and methods: In this study, MTT assay, plate colony formation assays, soft agar assay, and EdU assay were employed to evaluate the anti-proliferation effects of LAS. Apoptosis and cell cycle distribution were detected by flow cytometry. The molecular mechanism was predicted by performing RNA sequencing and verified by using immunoblotting assays. Breast cancer organiods derived from patient-derived xenografts model and MDA-MB-231 xenograft mouse model were established to assess the effect of LAS. Results: Our study showed that LAS treatment significantly suppressed cell viability of 5 breast cancer cell lines, with the IC50 value of approximately 1-5 µM. LAS also inhibitied the clonogenic ability and DNA synthesis of breast cancer cells, Moreover, LAS induced apoptosis and G2/M cell cycle arrest in SK-BR-3 and MDA-MB-231 cells. Notably, transcriptomic analysis predicted the mechanistic involvement of PLK1 in LAS-suppressed breast cancer progression. Our experiment data further verified that LAS reduced PLK1 mRNA and protein expression in breast cancer, accompanied by downregulating CDC25C and AKT phosphorylation. Ultimately, we confirmed that LAS inhibit breast cancer growth via inhibiting PLK1 pathway in vivo. Conclusions: Collectively, our findings revealed that LAS inhibits breast cancer progression via regulating PLK1 pathway, which provids scientific evidence for the use of traditional Chinese medicine in cancer therapy.

Dihydrocapsaicin suppresses the STING-mediated accumulation of ROS and NLRP3 inflammasome and alleviates apoptosis after ischemia-reperfusion injury of perforator skin flap.

Avascular necrosis frequently occurs as a complication following surgery involving the distal perforator flap. Dihydrocapsaicin (DHC) can protect tissue from ischemia-reperfusion (I/R) injury, but its specific role in multizone perforator flaps remains unclear. In this study, the prospective target of DHC in the context of I/R injury was predicted using network pharmacology analysis. Flap viability was determined through survival area analysis, laser Doppler blood flow, angiograms, and histological examination. The expressions of angiogenesis, apoptosis, NLR family pyrin domain containing 3 (NLRP3) inflammasome, oxidative stress, and molecules related to cyclic guanosine monophosphate (GMP)-adenosine monophosphate synthase (cGAS)-interferon gene stimulant (STING) pathway were assessed using western blotting, immunofluorescence, TUNEL staining, and dihydroethidium (DHE) staining. Our finding revealed that DHC promoted the perforator flap survival, which involves the cGAS-STING pathway, oxidative stress, NLRP3 inflammasome, apoptosis, and angiogenesis. DHC induced oxidative stress resistance and suppressed the NLRP3 inflammasome, preventing apoptosis in vascular endothelial cells. Through regulation of STING pathway, DHC controlled oxidative stress in endothelial cells and NLRP3 levels in ischemic flaps. However, activation of the cGAS-STING pathway led to the accumulation of reactive oxygen species (ROS) and NLRP3 inflammasome, thereby diminishing the protective role of DHC. DHC enhanced the survival of multidomain perforator flaps by suppressing the cGAS-STING pathway, oxidative stress, and the formation of NLRP3 inflammasome. These findings unveil a potentially novel mechanism with clinical significance for promoting the survival of multidomain perforator flaps.

Targeting the PHF8/YY1 axis suppresses cancer cell growth through modulation of ROS.

High levels of mitochondrial reactive oxygen species (mROS) are linked to cancer development, which is tightly controlled by the electron transport chain (ETC). However, the epigenetic mechanisms governing ETC gene transcription to drive mROS production and cancer cell growth remain to be fully characterized. Here, we report that protein demethylase PHF8 is overexpressed in many types of cancers, including colon and lung cancer, and is negatively correlated with ETC gene expression. While it is well known to demethylate histones to activate transcription, PHF8 demethylates transcription factor YY1, functioning as a co-repressor for a large set of nuclear-coded ETC genes to drive mROS production and cancer development. In addition to genetically ablating PHF8, pharmacologically targeting PHF8 with a specific chemical inhibitor, iPHF8, is potent in regulating YY1 methylation, ETC gene transcription, mROS production, and cell growth in colon and lung cancer cells. iPHF8 exhibits potency and safety in suppressing tumor growth in cell-line- and patient-derived xenografts in vivo. Our data uncover a key epigenetic mechanism underlying ETC gene transcriptional regulation, demonstrating that targeting the PHF8/YY1 axis has great potential to treat cancers.

[Analysis of efficacy and prognosis of neoadjuvant chemotherapy and （or） surgery plus radiotherapy for hypopharyngeal squamous cell carcinoma].

Objective:To analyze the risk factors that affect the prognosis of patients with hypopharyngeal squamous cell carcinoma（HPSCC） and to compare the efficacy of surgical resection followed by adjuvant radiotherapy（SR） with that of neoadjuvant therapy consisting of platinum-based chemotherapy and fluorouracil combined with either cetuximab or nimotuzumab, followed by SR. The study also aimed to evaluate the overall survival（OS） of patients, their postoperative eating function, tracheostomy decannulation rate, and tumor response to the two neoadjuvant chemotherapies. Methods:A retrospective analysis was performed on the medical records of HPSCC patients who received SR or neoadjuvant therapy followed by SR treatment at the Shanghai General Hospital from 2012 to 2019 and had not undergone any prior treatment. The prognostic factors were analyzed, and the survival analysis of patients who underwent SR treatment with two neoadjuvant chemotherapy regimens was performed. Results:A total of 108 patients were included in the study. The results of the univariate analysis showed that gender（P=0.850） had no significant correlation with the survival rate of HPSCC patients who underwent SR. However, age, smoking history, alcohol consumption history, platelet-to-lymphocyte ratio（PLR）, neutrophil-to-lymphocyte ratio（NLR）, T stage, N stage, neoadjuvant therapy with either cetuximab or nimotuzumab combined with platinum-based chemotherapy and fluorouracil, and histological grade were significantly associated with prognosis（P<0.05）. The multivariate analysis revealed that smoking history, histological grade, and neoadjuvant therapy with either cetuximab or nimotuzumab combined with platinum-based chemotherapy and fluorouracil were independent risk factors affecting the prognosis of HPSCC（P<0.05）. Patients who received neoadjuvant therapy had longer OS than those who underwent SR only（P<0.001）. There was no significant difference in tumor response to the two neoadjuvant therapies and in OS（P>0.05）, and there was no significant difference in the rate of oral feeding and tracheostomy decannulation among the three treatment groups（P>0.05）. Conclusion:Univariate analysis showed that age at tumor onset, smoking history, alcohol consumption history, NLR, PLR, T stage, N stage, whether receiving neoadjuvant chemotherapy, and pathological grade were associated with the prognosis of HPSCC patients receiving SR treatment. Multivariate analysis showed that smoking history, pathological grade, and neoadjuvant chemotherapy were independent risk factors affecting the prognosis. Neoadjuvant chemotherapy with cetuximab or nimotuzumab can prolong the OS of patients, providing a certain basis and reference for the treatment of HPSCC.

Baicalin promotes random-pattern skin flap survival by inducing autophagy via AMPK-regulated TFEB nuclear transcription.

The random-pattern skin flap is a generally used technique to cover the soft tissue defect, while its application is often constrained by complications after the flap transplant. Necrosis of the flap remains a principal obstacle. The purpose of this study was to investigate the effect of Baicalin on skin flap survival and its mechanism. First of all, we discovered that administering Baicalin stimulated cell migration and boosted the formation of capillary tubes in human umbilical vein endothelial cells. Then, we detected that Baicalin reduced apoptosis-induced oxidative stress by using western blot and oxidative stress test kit. After that, we observed that Baicalin increased autophagy and utilized 3MA to block autophagy augmentation substantially reversing the effects of Baicalin therapy. Furthermore, we uncovered the underlying mechanisms of Baicalin-induced autophagy via AMPK-regulated TFEB nuclear transcription. Finally, our in vivo experiment findings showed that Baicalin reduces oxidative stress, inhibits apoptosis, promotes angiogenesis, and boosts the levels of autophagy. After autophagy was blocked, substantially reversing the effects of Baicalin therapy. Our study indicated that Baicalin-induced autophagy via AMPK regulated TFEB nuclear transcription and then promotes angiogenesis and against oxidative stress and apoptotic promotes skin flap survival. These findings highlight the therapeutic potential for the clinical application of Baicalin in the future.

Electroacupuncture Increases the Expression of Gas7 and NGF in the Prefrontal Cortex of Male Rats with Focal Cerebral Ischemia.

OBJECTIVE: To investigate the potential mechanisms underlying the migration of endogenous neural stem cells (eNSCs) to the frontal cortex to differentiate into neurons, and to monitor the effect of electroacupuncture (EA) regulation of focal cerebral ischemia (FCI) in rats on the expression of growth arrest-specific protein 7 (Gas7) and nerve growth factor (NGF) in the prefrontal cortex (PFC). METHODS: Randomly, forty-eight male Sprague-Dawley rats were divided into four groups: Normal, Sham operation, Model, and EA. The right middle cerebral artery was embolized utilizing the thread-embolism technique. In the EA group, "Baihui" and "Zusanli" points were treated with electroacupuncture for 30 minutes, once a day, for 21 days. Nissl staining revealed the neuronal morphology of the PFC. Using immunohistochemistry and Western blot, the expression of Gas7 and NGF in the right PFC was observed. RESULTS: Nissl staining showed clear PFC neurons with centered nuclei and distinct nucleoli in the Normal and Sham groups. In the Model group, the PFC nuclei were distinctively smaller. The neuronal morphology in the EA group resembled that of the Normal group. Results from Western blot and immunohistochemistry were comparable. The expression of Gas7 and NGF in the Sham surgery group did not differ significantly from the Normal group. However, the expression of Gas7 and NGF in the Model group was significantly lower than in the Normal group. The expression of Gas7 and NGF was significantly higher in the EA group than in the Model group. CONCLUSIONS: EA can increase the expressions of Gas7 and NGF in the ischemic prefrontal cortex, which may be one of the mechanisms by which EA promotes the differentiation of eNSCs into neurons in the injured area.

Facile synthesis of chitosan-tartaric acid biosorbents for removal of Cu(II) and Cd(II) from water and tea beverages.

Consumption of water and tea beverages leads to the intake of heavy metals by humans. Development of technology for decontamination greatly reduces the risks of the heavy metal exposure. In this study, environment-friendly chitosan-tartaric acid biosorbents (CTBs) were synthesized by a facile one-step cross-linking strategy to mitigate the Cu(II) and Cd(II) contamination in water and tea beverages. The cross linkage of tartaric acid and chitosan endowed CTBs with excellent properties in aspects of surface roughness, mechanical strength, and acid resistance. Adsorption performance and mechanism of CTBs were studied, and the Langmuir isotherm model and pseudo-second-order kinetic model were adhered during adsorption. Up to 90 % removal efficiencies of Cu(II) and Cd(II) from water and tea beverages by CTBs were achieved. Moreover, the adsorption showed only a slight reduction in the quality of tea beverages. This study offers a new insight for reduction of heavy metals-pollution in beverages.

Identification of differential volatile and non-volatile compounds in coffee leaves prepared from different tea processing steps using HS-SPME/GC-MS and HPLC-Orbitrap-MS/MS and investigation of the binding mechanism of key phytochemicals with olfactory and taste receptors using molecular docking.

Tea processing steps affected the proximate composition, enzyme activity and bioactivity of coffee leaves; however, the effects of different tea processing steps on the volatiles, non-volatiles, color, and sensory characteristics of coffee leaves have yet been demonstrated. Here the dynamic changes of volatile and non-volatile compounds in different tea processing steps were investigated using HS-SPME/GC-MS and HPLC-Orbitrap-MS/MS, respectively. A total of 53 differential volatiles (alcohol, aldehyde, ester, hydrocarbon, ketone, oxygen heterocyclic compounds, phenol, and sulfur compounds) and 50 differential non-volatiles (xanthone, flavonoid, organic acid, amino acid, organic amine, alkaloid, aldehyde, and purine et al.) were identified in coffee leaves prepared from different processing steps. Kill-green, fermentation, and drying steps significantly influenced the volatiles; however, kill-green, rolling, and drying steps significantly affected the color of coffee leaves and their hot water infusion. The coffee leaf tea that was prepared without the kill-green process was found to have a more pleasant taste as compared to the tea that was prepared with the kill-green process. This can be attributed to the fact that the former contained lower levels of flavonoids, chlorogenic acid, and epicatechin, but had higher levels of floral, sweet, and rose-like aroma compounds. The binding interactions between the key differential volatile and non-volatile compounds and the olfactory and taste receptors were also investigated. The key differential volatiles, pentadecanal and methyl salicylate generate fresh and floral odors by activating olfactory receptors, OR5M3 and OR1G1, respectively. Epicatechin showed a high affinity to the bitter receptors, including T2R16, T2R14, and T2R46. Since the specific content of differential compounds in different samples varies greatly, the dose-effect and structure-function relationships of these key compounds and the molecular mechanism of the odor and taste of coffee leaf tea need to be further studied.

Antitumor pharmacological research in the era of personalized medicine.

Anticancer drug discovery has yielded unprecedented progress in recent decades, resulting in the approval of innovative treatment options for patients and the successful implementation of personalized medicine in clinical practice. This remarkable progress has also reshaped the research scope of pharmacological research. This article, as a tribute to cancer research at Shanghai Institute of Materia Medica in celebration of the institute's 90th birthday, provides an overview of the conceptual revolution occurring in anticancer therapy, and summarizes our recent progress in the development of molecularly targeted therapeutics and exploration of new strategies in personalized medicine. With this review, we hope to provide a glimpse into how antitumor pharmacological researchers have embraced the new era of personalized medicine research and to propose a future path for anticancer drug discovery and pharmacological research.

The effect of electroacupuncture on the expression of Sirt1 and STAT3 in hippocampus and amygdala of vascular dementia rats.

OBJECTIVE: Inflammation has long been considered a key factor in learning and memory impairment in patients with vascular dementia (VaD). Studies have confirmed that electroacupuncture can improve the learning and memory impairment of patients with VaD by reducing inflammation, but the specific mechanism of this effect is still unclear. The aim of this study was to explore the underlying mechanism of electroacupuncture in the treatment of VaD. METHODS: The vascular dementia animal model was established by bilateral occlusion of common carotid arteries, and electroacupuncture treatment was given at Baihui (DU20) and Zusanli (ST36). The morris water maze (MWM) was used to test the spatial learning and memory ability of rats in each group. To evaluate the expression of Sirtuin1 (Sirt1), Signal transducer and activator of transcription 3 (STAT3) and inflammatory cytokine (IL-17) in the hippocampus and amygdala, immunohistochemistry and western blot were performed. RESULTS: The MWM test and Nissl staining results show that electroacupuncture can significantly improve the learning and memory impairment of VaD rats, and can repair damaged neurons. Immunohistochemistry and western blot results showed that electroacupuncture could enhance the expression of sirt1 in VaD rats, on the contrary, the expression of STAT3 and IL-17 was reduced due to electroacupuncture. CONCLUSIONS: The result suggests that electroacupuncture can suppress inflammation through the Sirt1/STAT3 pathway and improve spatial learning and memory in VaD rats.

Encapsulation of selenium-containing peptides in xanthan gum-lysozyme nanoparticles as a powerful gastrointestinal delivery system.

In this study, nanoparticles (NPs) prepared with xanthan gum and lysozyme were established as a powerful delivery system for two Se-containing peptides: TSeMMM (STP) and SeMDPGQQ (SHP). NPs-STP and NPs-SHP had relatively small particle sizes (145 nm and 148 nm) and negative zeta potentials (-47 mV and -49 mV). The encapsulation efficiency of NPs-STP and NPs-SHP was determined to be 34.35% and 41.35%, respectively. The stability and antioxidant activity of Se-containing peptides were greatly enhanced due to encapsulation. NPs-STP and NPs-SHP exhibited controlled release of Se-containing peptides under in vitro gastrointestinal conditions. NPs-STP and NPs-SHP showed low toxicity and entered Caco-2 cells through clathrin-mediated endocytosis, contributing to a significant increase in the apparent permeability coefficient of STP (2.19 × 10-6 cm/s) and SHP (2.21 × 10-6 cm/s). Thus, NPs-STP and NPs-SHP are considered promising delivery systems for Se-containing peptides and have good potential applications in the food and pharmaceutical industries.

Effect of ultrasonic treatment on the stability and release of selenium-containing peptide TSeMMM-encapsulated nanoparticles in vitro and in vivo.

Rice selenium-containing peptide TSeMMM (T) with immunomodulatory functions was isolated from selenium-enriched rice protein hydrolysates. However, its biological activity is difficult to be protected in complex digestive environments. In this study, T was encapsulated within zein and gum arabian (GA) through ultrasound treatment to improve its bioactivity and bioavailability. The zein@T/GA nanoparticles were formed using ultrasonic treatment at 360 W for 5 min with a 59.9% T-encapsulation efficiency. In vitro digestion showed that the cumulative release rate of zein@T/GA nanoparticles reached a maximum of 80.69% after 6 h. In addition, short-term animal studies revealed that the nanoparticles had an effect on the levels of tissue glutathione and improved peptides' oral bioavailability. Conclusively, these findings suggest that the ultrasonicated polysaccharide/protein system is suitable for encapsulating active small molecular peptides. Furthermore, it provides a novel foundation for studying the bioavailability of active substances in functional foods.

Fabrication and characterization of ß-carotene emulsions stabilized by soy oleosin and lecithin mixtures with a composition mimicking natural soy oleosomes.

Natural soy oleosomes are known to have a remarkable stability, given the advantage of their sophisticated membrane. The aim of the present study is to examine the concept of fabricating a ß-carotene emulsion stabilized by soy oleosin (OLE) and lecithin (LEC) mixtures mimicking the membrane composition of soy oleosomes while providing preferable stability and bioaccessibility. For this, the fabricated emulsion was characterized in terms of droplet size distribution, and emulsion structure, stability and digestion (release and absorption of lipophilic ß-carotene). Compared to SPI/LEC (10 : 1) stabilized emulsions, the OLE/LEC (10 : 1) mixture stabilized emulsion exhibited the highest emulsifying activity index (EAI) and emulsifying stability index (ESI) values, and higher encapsulation efficiency. Results show that the ß-carotene emulsion stabilized by OLE and LEC mixtures at the ratio of 10 : 1 (w/w) has the most uniform droplet distribution and highest stability. The in vitro gastrointestinal digestion test revealed that the ß-carotene emulsion stabilized by OLE and LEC mixtures was digested more rapidly than the emulsion stabilized by soy protein isolate (SPI) and LEC mixtures. In turn, the bioaccessibility and cellular uptake of ß-carotene were enhanced, resulting in a higher absorption, a desirable feature of nutrition delivery systems. Our results demonstrated a promising way to fabricate emulsions mimicking natural soy oleosomes.

[Analysis of spectrum-activity relationship among antioxidant parts of Lycii Fructus using three different chemometrics methods].

The chemical components of Lycii Fructus were analyzed by liquid chromatography( LC) and mass spectrometry( MS for the establishment of spectrum-activity relationship,on the basis of which its antioxidant active ingredients were determined. In this experiment,Lycii Fructus was extracted with different solvents and then separated into 80 samples by macroporous adsorption resin and reversed-phase chromatography,respectively. The antioxidant components were enriched into 11 samples and their scavenging abilities against DPPH free radical and ferric ion reducing antioxidant power( FRAP) were significantly stronger than those before the treatment( P<0. 05). The spectrum-activity relationship regarding the antioxidant activity in vitro of Lycii Fructus was established by Pearson correlation analysis,orthogonal partial least squares( OPLS) and elastic net regression. Six chromatographic peaks greatly contributing to the antioxidant activity in vitro of Lycii Fructus were identified as rutin( P6),quercetin( P35),scopoletin( P14),N-cis-feruloyl-4-O-ß-D-glucopyranosyl-tyramine or N-( 4-O-ß-D-glucopyranosyl-trans-feruloyl)-tyramine( P8), ferulic acid( P13) and1,3,5-dihydroxy-2-isoprenyl-3-xanthone( P23). The active components associated with free radical scavenging were rutin and quercetin both belonging to flavonoids. The reduction of Fe3+was based on phenylpropanoids such as ferulic acid,scopoletin,xanthone and phenolic amides. These results indicated that the antioxidant activity of Lycii Fructus was ascribed to the synergistic action of different products through different ways. Besides,the data analysis model should be chosen carefully for the establishment of spectrum-activity relationship,thus ensuring the reliability of results.

Novel green chitosan-pectin gel beads for the removal of Cu(II), Cd(II), Hg(II) and Pb(II) from aqueous solution.

Chitosan-pectin gel beads (CPBs) were synthesized via a facile and green method and applied to remove heavy metals from aqueous solution. The structural characteristics of CPBs were investigated by SEM and FTIR, the mechanical strength of CPBs was measured by Texture Analyzer and the stability of CPBs was evaluated in acidic solution. To study the adsorption characteristics, the effect of pH, contact time, initial heavy metals concentration, temperature, adsorption mechanism and regeneration were systematically investigated. The adsorption kinetics fitted well pseudo-second-order model, and the adsorption isotherms were well described by Langmuir model. The maximum adsorption capacities of Cu(II), Cd(II), Hg(II) and Pb(II) were 169.4, 177.6, 208.5 and 266.5 mg/g, respectively. The adsorption-desorption experiments revealed that the CPBs exhibited a great reusability. Thus, the synthesized CPBs in this study had the potential to be utilized as an environment-friendly and green adsorbent for the removal of heavy metals.

Idiopathic mesenteric phlebosclerosis: clinical and CT imaging characteristics.

BACKGROUND: The aim of our study was to evaluate the clinical characteristics and computed tomography (CT) imaging findings of idiopathic mesenteric phlebosclerosis (IMP). METHODS: From January 2013 to May 2019, the clinical data of 10 patients diagnosed with IMP were analyzed retrospectively. Computed tomography angiography (CTA) and colonoscopy were performed in all 10 patients. All CT imaging findings were evaluated by three radiologists, including the form and distribution of calcification, the bowel's thickness, and the surrounding fat gap. The calcification score was calculated according to the extent of the involved mesenteric veins. The colonic wall thickness was defined as the average value of the thickest and thinnest regions of the intestinal wall. The correlation between the calcification scores and the colonic wall thickness was analyzed using Spearman's correlation analysis. RESULTS: All 10 patients were male with an average age of 59.6 years (range, 51-83 years). The average smoking index was 712 (range, 0-1,800). Among them, 7 patients had a history of long-term excessive daily intake of medicinal liquor or Chinese herbal medicine. Clinical symptoms of abdominal pain, diarrhea, bloating, and nausea were found. Colonoscopy showed dark purple discolorations of the edematous mucosa, engorged blood vessels, extensive erosion, ulceration, and multi-focal nodular surface in all patients. CT demonstrated colonic wall thickening, calcification along the mesenteric vein, and blurry surrounding fat gap in all 10 patients. Mesenteric venous calcification involved the terminal ileum, the ascending and transverse colon in all patients, and the descending colon and sigmoid colon's involvement in two patients. A total of 33 segments of the intestinal wall were involved. The median calcification score was 6 points, the mean thickness of the colonic wall was 10.73±3.22 mm, and there was no significant correlation (P=0.782) between calcification score and thickness of the colonic wall. CONCLUSIONS: The main features of IMP are mesenteric venous calcification, colonic wall thickness, and pericolic fat stranding, and there is no correlation between calcification score and colonic wall thickness. Therefore, CT imaging combined with colonoscopy can improve the diagnostic accuracy of IMP.

Identification of miRNA-mRNA Regulatory Modules Involved in Lipid Metabolism and Seed Development in a Woody Oil Tree (Camellia oleifera).

Tea oil camellia (Camellia oleifera), an important woody oil tree, is a source of seed oil of high nutritional and medicinal value that is widely planted in southern China. However, there is no report on the identification of the miRNAs involved in lipid metabolism and seed development in the high- and low-oil cultivars of tea oil camellia. Thus, we explored the roles of miRNAs in the key periods of oil formation and accumulation in the seeds of tea oil camellia and identified miRNA-mRNA regulatory modules involved in lipid metabolism and seed development. Sixteen small RNA libraries for four development stages of seed oil biosynthesis in high- and low-oil cultivars were constructed. A total of 196 miRNAs, including 156 known miRNAs from 35 families, and 40 novel miRNAs were identified, and 55 significantly differentially expressed miRNAs were found, which included 34 upregulated miRNAs, and 21 downregulated miRNAs. An integrated analysis of the miRNA and mRNA transcriptome sequence data revealed that 10 miRNA-mRNA regulatory modules were related to lipid metabolism; for example, the regulatory modules of ath-miR858b-MYB82/MYB3/MYB44 repressed seed oil biosynthesis, and a regulation module of csi-miR166e-5p-S-ACP-DES6 was involved in the formation and accumulation of oleic acid. A total of 23 miRNA-mRNA regulatory modules were involved in the regulation of the seed size, such as the regulatory module of hpe-miR162a_L-2-ARF19, involved in early seed development. A total of 12 miRNA-mRNA regulatory modules regulating growth and development were identified, such as the regulatory modules of han-miR156a_L+1-SPL4/SBP2, promoting early seed development. The expression changes of six miRNAs and their target genes were validated using quantitative real-time PCR, and the targeting relationship of the cpa-miR393_R-1-AFB2 regulatory module was verified by luciferase assays. These data provide important theoretical values and a scientific basis for the genetic improvement of new cultivars of tea oil camellia in the future.

Optimization of ultrasonic-assisted extraction conditions for bioactive components from coffee leaves using the Taguchi design and response surface methodology.

Coffee leaves contain various bioactive compounds that are beneficial for human health. However, there are very limited researches related to the extraction of the bioactive phytochemicals from coffee leaves. In the present study, the extraction conditions for bioactive components from coffee leaves were optimized using Taguchi design and response surface methodology (RSM). Taguchi design was used to screen significant factors that affected the yield of phytochemicals including trigonelline, caffeine, chlorogenic acids, mangiferin, and rutin, total phenolic content (TPC) and antioxidant activity. Sequentially, a Box-Behnken design (BBD) was used to optimize the extraction conditions. Three factors including Liquid-to-solid (L:S) ratio, ethanol concentration, and extraction temperature that significantly affected most of the phytochemical yields and antioxidant activity were selected from the six variables using Taguchi design. The optimal extraction conditions obtained from RSM were 30.3:1 L:S ratio, 54.5% ethanol, and 80 °C when simultaneously considered four responses, including TPC, the yields of mangiferin and 5-CQA and DPPH scavenging capacity. Under the optimal conditions, the experimental results for the above four responses were 62.1 mg gallic acid/g, 4.1 mg/g, 11.4 mg/g, and 356.9 µmol Trolox/g, respectively, which were close to the predicted values. About 97% of phytochemicals can be extracted in the first two times of extraction. In conclusion, the combination of Taguchi design and response surface methodology can be successfully used to screen and optimize the significant factors that affected the bioactive components extracted from coffee leaves. PRACTICAL APPLICATION: Coffee leaves, the byproducts of coffee plants, are considered no- or low-value although it has a long history for using them as tea-like beverage and ethnomedicine by locals in the coffee plant growing countries. Bioactive components extracted from coffee leaves can be used as ingredients in functional beverages, functional food, and natural health products. These applications will add values to coffee leaves as well as increase the incomes of coffee farmers and workers.

Astragaloside IV inhibits astrocyte senescence: implication in Parkinson's disease.

BACKGROUND: Senescent astrocytes have been implicated in the aging brain and neurodegenerative disorders, including Parkinson's disease (PD). Astragaloside IV (AS-IV) is an antioxidant derivative from a traditional Chinese herbal medicine Astragalus membraneaceus Bunge and exerts anti-inflammatory and longevity effects and neuroprotective activities. However, its effect on astrocyte senescence in PD remains to be defined. METHODS: Long culture-induced replicative senescence model and lipopolysaccharide/1-methyl-4-phenylpyridinium (LPS/MPP+)-induced premature senescence model and a mouse model of PD were used to investigate the effect of AS-IV on astrocyte senescence in vivo and in vitro. Immunocytochemistry, qPCR, subcellular fractionation, flow cytometric analyses, and immunohistochemistry were subsequently conducted to determine the effects of AS-IV on senescence markers. RESULTS: We found that AS-IV inhibited the astrocyte replicative senescence and LPS/MPP+-induced premature senescence, evidenced by decreased senescence-associated ß-galactosidase activity and expression of senescence marker p16, and increased nuclear level of lamin B1, and reduced pro-inflammatory senescence-associated secretory phenotype. More importantly, we showed that AS-IV protected against the loss of dopamine neurons and behavioral deficits in the mouse model of PD, which companied by reduced accumulation of senescent astrocytes in substantia nigra compacta. Mechanistically, AS-IV promoted mitophagy, which reduced damaged mitochondria accumulation and mitochondrial reactive oxygen species generation and then contributed to the suppression of astrocyte senescence. The inhibition of autophagy abolished the suppressive effects of AS-IV on astrocyte senescence. CONCLUSIONS: Our findings reveal that AS-IV prevents dopaminergic neurodegeneration in PD via inhibition of astrocyte senescence through promoting mitophagy and suggest that AS-IV is a promising therapeutic strategy for the treatment of age-associated neurodegenerative diseases such as PD.