Six new sesquineolignans from the stems of Akebia quinate and their diacylglycerol acyltransferase activity.

Six new sesquineolignans (1-6), have been isolated and elucidated from the stems of Akebia quinate together with five known analogues (7-11). Their structures were elucidated on the basis of comprehensive analysis of UV, IR, NMR, HRESIMS and CD spectroscopy experiments. All the isolates were evaluated for in vitro inhibitory activity against DGAT1 and DGAT2. Among them, compounds 1-11 were found to exhibit selective inhibitory activity on DGAT1 with IC50 values ranging from 60.4 ± 1.3 to 84.6 ± 1.3 µM. Besides, the potential binding sites of 1 were predicted by molecular docking.

Integrative Effects of Transcutaneous Electrical Acustimulation and Autonomic-Endocrine Mechanisms on Postprocedural Recovery in Patients With Endoscopic Retrograde Cholangio-Pancreatography.

OBJECTIVES: This study aimed to investigate the integrative effects and mechanisms of transcutaneous electrical acustimulation (TEA) on postprocedural recovery from endoscopic retrograde cholangio-pancreatography (ERCP). MATERIALS AND METHODS: A total of 86 patients for elective ERCP were randomly ordered to receive TEA (n = 43) at acupoints PC6 and ST36 or Sham-TEA (n = 43) at sham points from 24 hours before ERCP (pre-ERCP) to 24 hours after ERCP (PE24). Scores of gastrointestinal (GI) motility-related symptoms and abdominal pain, gastric slow waves, and autonomic functions were recorded through the spectral analysis of heart rate variability; meanwhile, circulatory levels of inflammation cytokines of tumor necrosis factor-α (TNF-α) and interleukin (IL)-10 and GI hormones of motilin, ghrelin, cholecystokinin (CCK), and vasoactive intestinal peptide (VIP) were assessed by enzyme-linked immunosorbent assay. RESULTS: 1) TEA, but not Sham-TEA, decreased the post-ERCP GI motility-related symptom score (2.4 ± 2.6 vs 7.9 ± 4.6, p < 0.001) and abdominal pain score (0.5 ± 0.7 vs 4.1 ± 2.7, p < 0.001) at PE24, and decreased the post-ERCP hospital day by 20.0% (p ＜0.05 vs Sham-TEA); 2) TEA improved the average gastric percentage of normal slow waves and dominant frequency by 34.6% and 33.3% at PE24, respectively (both p < 0.001 vs Sham-TEA); 3) TEA, but not Sham-TEA, reversed the ERCP-induced increase of TNF-α but not IL-10 at PE24, reflected as a significantly lower level of TNF-α in the TEA group than in the Sham-TEA group (1.6 ± 0.5 pg/mL vs 2.1 ± 0.9 pg/mL, p ＜ 0.01); 4) compared with Sham-TEA, TEA increased vagal activity by 37.5% (p ＜ 0.001); and 5) TEA caused a significantly higher plasma level of ghrelin (1.5 ± 0.8 ng/ml vs 1.1 ± 0.7 ng/ml, p ＜ 0.05) but not motilin, VIP, or CCK than did Sham-TEA at PE24. CONCLUSION: TEA at PC6 and ST36 accelerates the post-ERCP recovery, reflected as the improvement in GI motility and amelioration of abdominal pain, and suppression of the inflammatory cytokine TNF-α may mediate through both autonomic and ghrelin-related mechanisms.

Euphorbia pekinensis Rupr. roots: a comprehensive review of botany, traditional uses, phytochemistry, pharmacology, quality control, and toxicology.

Euphorbia pekinensis Rupr. is a traditional herb generally distributed in most areas of China, north Korea and Japan. The dried roots of Euphorbia pekinensis Rupr. (REP), famous as 'Jing Da Ji' () have been applied as traditional herb medicines to expel water and rheum; disperse swelling, dissipate binds and to treat edoema, pleural effusions, uraemia, nephritis, cirrhosis with ascites, as well as other diseases. Recent advances in botany, traditional uses, phytochemistry, pharmacology, quality control, and toxicology of E. pekinensis roots are methodically outlined and current limitations as well as future perspectives also are discussed in order to guide scientifical investigation and rational application of REP. Up to now, 79 structurally diverse compounds have been obtained and characterised from REP, principally including diterpenoids, triterpenoids, tannins, phenols, and 29 volatile constituents. Among which, diterpenoids are considered as primary characteristic and active constituents. The extracts and individual compounds from REP have demonstrated significant pharmacological effects such as diuretic and purgative, anti-inflammatory, and cytotoxic effects. REP are widely used in traditional medicine due to diverse chemical constituents with obvious pharmacological effects. Modern phytochemical and pharmacological studies justified and explained relevant traditional uses of REP and offer worthy clues for new medical fields of industrial application. Nevertheless, a great number of thorough and detailed investigations should be carried out in active constituents, mechanisms of action, quality-marker, toxicology assessment, and detoxification mechanisms of REP.

Effect of high-fat diet on the fatty acid profiles of brain in offspring mice exposed to maternal gestational diabetes mellitus.

OBJECTIVE: Fatty acids play a critical role in the proper functioning of the brain. This study investigated the effects of a high-fat (HF) diet on brain fatty acid profiles of offspring exposed to maternal gestational diabetes mellitus (GDM). METHODS: Insulin receptor antagonist (S961) and HF diet were used to establish the GDM animal model. Brain fatty acid profiles of the offspring mice were measured by gas chromatography at weaning and adulthood. Protein expressions of the fatty acid transport pathway Wnt3/ß-catenin and the target protein major facilitator superfamily domain-containing 2a (MFSD2a) were measured in the offspring brain by Western blot. RESULTS: Maternal GDM increased the body weight of male offspring (P < 0.05). In weaning offspring, factorial analysis showed that maternal GDM increased the monounsaturated fatty acid (MUFA) percentage of the weaning offspring's brain (P < 0.05). Maternal GDM decreased offspring brain arachidonic acid (AA), but HF diet increased brain linoleic acid (LA) (P < 0.05). Maternal GDM and HF diet reduced offspring brain docosahexaenoic acid (DHA), and the male offspring had higher DHA than the female offspring (P < 0.05). In adult offspring, factorial analysis showed that HF diet increased brain MUFA in offspring, and male offspring had higher brain MUFA than female offspring (P < 0.05). The HF diet increased brain LA in the offspring. Male offspring had higher level of AA than female offspring (P < 0.05). HF diet reduced DHA in the brains of female offspring. The brain protein expression of ß-catenin and MFSD2a in both weaning and adult female offspring was lower in the HF + GDM group than in the CON group (P < 0.05). CONCLUSIONS: Maternal GDM increased the susceptibility of male offspring to HF diet-induced obesity. HF diet-induced adverse brain fatty acid profiles in both male and female offspring exposed to GDM.

Gestational Diabetes Mellitus Remodels the Fetal Brain Fatty Acid Profile Through Placenta-Brain Lipid Axis in C57BL/6J Mice.

BACKGROUND: Polyunsaturated fatty acids (PUFAs), especially docosahexaenoic acid (DHA), are critical for proper fetal brain growth and development. Gestational diabetes mellitus (GDM) could affect maternal-fetal fatty acid metabolism. OBJECTIVE: This study aimed to explore the effect of GDM and high-fat (HF) diet on the DHA transport signaling pathway in the placenta-brain axis and fatty acid concentrations in the fetal brain. METHODS: Insulin receptor antagonist (S961) and HF diet were used to establish an animal model of GDM. Eighty female C57BL/6J mice were randomly divided into control (CON), GDM, HF, and HF+GDM groups. The fatty acid profiles of the maternal liver and fetal brain were analyzed by gas chromatography. In addition, we analyzed the protein amounts of maternal liver fatty acid desaturase (FADS1/3), elongase (ELOVL2/5) and the regulatory factor sterol-regulatory element-binding protein (SREBP)-1c, and the DHA transport signaling pathway (Wnt3/ß-catenin/MFSD2a) of the placenta and fetal brain using western blotting. RESULTS: GDM promoted the decrease of maternal liver ELOVL2, ELOVL5, and SREBP-1c. Accordingly, we observed a significant decrease in the amount of maternal liver arachidonic acid (AA), DHA, and total n-3 PUFA and n-6 PUFA induced by GDM. GDM also significantly decreased the amount of DHA and n-3 PUFA in the fetal brain. GDM downregulated the Wnt3/ß-catenin/MFSD2a signaling pathway, which transfers n-3 PUFA in the placenta and fetal brain. The HF diet increased n-6 PUFA amounts in the maternal liver, correspondingly increasing linoleic acid, gamma-linolenic acid, AA, and total n-6 PUFA in the fetal brain, but decreased DHA amount in the fetal brain. However, HF diet only tended to decrease placental ß-catenin and MFSD2a amounts (P = 0.074 and P = 0.098, respectively). CONCLUSIONS: Maternal GDM could affect the fatty acid profile of the fetal brain both by downregulating the Wnt3/ß-catenin/MFSD2a pathway of the placental-fetal barrier and by affecting maternal fatty acid metabolism.

Effects of dietary PUFA patterns and FADS genotype on breast milk PUFAs in Chinese lactating mothers.

BACKGROUND: Breastfeeding affects the growth and development of infants, and polyunsaturated fatty acids (PUFAs) play a crucial role in this process. To explore the factors influencing the PUFA concentration in breast milk, we conducted research on two aspects: dietary fatty acid patterns and single nucleotide polymorphisms (SNPs) in maternal fatty acid desaturase genes. METHODS: Three hundred seventy Chinese Han lactating mothers were recruited. A dietary semi-quantitative food frequency questionnaire (FFQ) was used to investigate the dietary intake of lactating mothers from 22 to 25 days postpartum for 1 year. Meanwhile, breast milk samples were collected from the participants and tested for the concentrations of 8 PUFAs and 10 SNP genotypes. We sought to determine the effect of dietary PUFA patterns and SNPs on breast milk PUFAs. We used SPSS 24.0 statistical software for data analysis. Statistical tests were all bilateral tests, with P < 0.05 as statistically significant. RESULTS: Under the same dietary background, PUFA contents in breast milk expressed by most major allele homozygote mothers tended to be higher than that expressed by their counterparts who carried minor allele genes. Moreover, under the same gene background, PUFA contents in breast milk expressed by the mother's intake of essential PUFA pattern tended to be higher than that expressed by their counterparts who took the other two kinds of dietary. CONCLUSIONS: Our study suggests that different genotypes and dietary PUFA patterns affect PUFA levels in breast milk. We recommend that lactating mothers consume enough essential fatty acids to ensure that their infants ingest sufficient PUFAs.

Traditional uses, phytochemistry, pharmacology, toxicology, and quality control of Rhododendron dauricum L. leaves: A comprehensive review.

ETHNOPHARMACOLOGICAL RELEVANCE: Rhododendron dauricum L. is a traditional herb mainly distributed in the northeast China, Mongolia, Korea Peninsula, and Russia Far East. The dried leaves of Rhododendron dauricum L. (LRD), generally known "Man Shan Hong" have been traditionally applied as folk medicines to treat fever, copious phlegm, asthma, acute and chronic bronchitis, sore throat, dysentery, diabetes mellitus, cancer, and hypertension. To date, no comprehensive review on R. dauricum leaves has been published. AIM OF THE STUDY: Recent progresses in traditional use, phytochemistry, pharmacology, toxicology, and quality control of R. dauricum leaves are systematically presented and critically evaluated in order to provide scientifical basis for its reasonable utilization and further study. MATERIALS AND METHODS: All information about R. dauricum leaves were retrieved from internet scientific databases including Sci-Finder, Web of Science, PubMed, CNKI, Google Scholar, Elsevier, Wiley, ACS publications, SpringerLink, and the Chinese Pharmacopoeia between 1970 and 2022. Plant names were validated by "The Plant List" (http://www.theplantlist.org/). RESULTS: So far, 114 structurally diverse compounds have been isolated and identified from LRD, mainly including flavonoids, diterpenoids, triterpenoids, meroterpenoids, phenols, and 54 volatile components were identified from the essential oils of LRD. Among these, flavonoids are considered as characteristic components and major bioactive phytochemicals. The crude extracts and compounds from LRD have been reported to possess broad pharmacological effects including antitussive and expectorant, anti-inflammatory, anti-HIV, antibacterial, and cytotoxic effects, etc. CONCLUSIONS: As a traditional herb medicine, LRD have been used popularly. On the one hand, traditional uses of LRD provide valuable directions for current research; on the other hand, modern phytochemical and pharmacological studies verify the traditional uses to make its reasonable utilization. However, several defects such as active components determination, in vivo and clinical pharmacological evaluation, toxicology assessment, and quality control of LRD need further study.

Formation mechanisms and supervisory prediction of scaling in water supply pipelines: A review.

The scaling problem in the water supply pipeline will increase the resistance coefficient of the pipeline and the pressure of the water supply pipeline, which will not only affect the operation safety of the water supply pipeline, but also cause energy waste. The scale in the pipeline will also enrich heavy metal ions and pathogenic microorganisms, affecting the safety of water supply water quality and causing secondary pollution of water quality. At present, a lot of research has been done on the composition structure and crystallization process of the scale. The study found that calcite is the main component of the scale; the scale process is a heterogeneous nucleation process induced by heavy metal particles and their corrosion products in the pipeline. The introduction of electrochemical detection technology, density functional theory and molecular dynamics simulation has greatly improved the accuracy and timeliness of water scaling conditions detection and realized the visualization of scaling mechanism. In this paper, the measurement methods of the scale in the water supply pipeline and the corresponding material composition and crystal structure characteristics are reviewed, and the mechanism of the scale and the water quality conditions are summarized. At the end of this paper, based on summarizing the existing water quality scaling tendency evaluation methods, it is proposed to establish a water quality potential scaling risk assessment framework based on Puckorius scaling index (PSI) and electrochemical impedance spectroscopy (EIS) in the future.

Association of Prepregnancy Obesity and Remodeled Maternal-Fetal Plasma Fatty Acid Profiles.

Background: Fatty acids, especially polyunsaturated fatty acid (PUFA), are found abundantly in the brain and are fundamental for a fetus's growth. The fatty acid profiles of mothers and fetuses may be affected by maternal prepregnancy body mass index (pre-BMI), thus affecting fetal growth and development. Methods: A total of 103 mother-fetus pairs were divided into overweight/obese (OW, n = 26), normal weight (NW, n = 60), and underweight (UW, n = 17) groups according to pre-BMI. Fatty acid profiles in maternal and umbilical cord plasma were analyzed by gas chromatography. Results: The infant birth BMI z-score of the OW group was higher than that of the NW and UW groups (p < 0.05). The OW mothers had significantly higher plasma n-6 PUFA and n-6/n-3, but lower docosahexaenoic acid (DHA) and n-3 PUFA (p < 0.05). In cord plasma, the proportions of DHA and n-3 PUFA were lower in the OW group (p < 0.05), whereas the n-6/n-3 ratio was higher in the OW group (p < 0.05). The pre-BMI was negatively correlated with cord plasma DHA in all subjects (r = -0.303, p = 0.002), and the same negative correlation can be observed in the OW group (r = -0.561, p = 0.004), but not in the NW and UW groups (p > 0.05). The pre-BMI was positively correlated with cord plasma n-6/n-3 in all subjects (r = 0.325, p = 0.001), and the same positive correlation can be found in the OW group (r = 0.558, p = 0.004), but not in NW and UW groups (p > 0.05). Conclusions: Maternal pre-BMI was associated with the maternal-fetal plasma fatty acid profiles, whereas the adverse fatty acid profiles are more noticeable in the prepregnancy OW mothers.

Pan-Genome Analysis Reveals the Abundant Gene Presence/Absence Variations Among Different Varieties of Melon and Their Influence on Traits.

Melon (Cucumismelo L.) is an important vegetable crop that has been subjected to domestication and improvement. Several varieties of melons with diverse phenotypes have been produced. In this study, we constructed a melon pan-genome based on 297 accessions comprising 168 Mb novel sequences and 4,325 novel genes. Based on the results, there were abundant genetic variations among different melon groups, including 364 unfavorable genes in the IMP_A vs. LDR_A group, 46 favorable genes, and 295 unfavorable genes in the IMP_M vs. LDR_M group. The distribution of 709 resistance gene analogs (RGAs) was also characterized across 297 melon lines, of which 603 were core genes. Further, 106 genes were found to be variable, 55 of which were absent in the reference melon genome. Using gene presence/absence variation (PAV)-based genome-wide association analysis (GWAS), 13 gene PAVs associated with fruit length, fruit shape, and fruit width were identified, four of which were located in pan-genome additional contigs.

Integrative effects of transcutaneous electrical acustimulation on abdominal pain, gastrointestinal motility, and inflammation in patients with early-stage acute pancreatitis.

BACKGROUND/AIMS: Gastrointestinal (GI) dysmotility in acute pancreatitis (AP) aggravates inflammation and results in severe complications. This study aimed to explore effects and possible mechanisms of transcutaneous electrical acustimulation (TEA) on abdominal pain, GI dysmotility, and inflammation in AP patients. METHODS: Forty-two AP patients were blindly randomized to receive TEA (n = 21) at acupoints PC6 and ST36 or Sham-TEA (n = 21) at sham points for 2 days. Symptom scores, gastric slow waves, autonomic functions (assessed by spectral analysis of heart rate variability), circulatory levels of motilin, ghrelin, and TNF-α were measured before and after the treatment. Sixteen healthy controls (HCs) were also included without treatment for the assessment of gastric slow waves and biochemistry. KEY RESULTS: Compared with Sham-TEA, TEA decreased abdominal pain score (2.57 ± 1.78 vs. 1.33 ± 1.02, p < 0.05), bloating score (5.19 ± 1.21 vs. 0.76 ± 0.99, p < 0.001), the first defecation time (65.79 ± 19.51 h vs. 51.38 ± 17.19 h, p < 0.05); TEA, but not Sham-TEA, improved the percentage of normal gastric slow waves by 41.6% (p < 0.05), reduced AP severity score (5.52 ± 2.04 vs. 3.90 ± 1.90, p < 0.05) and serum TNF-α (7.59 ± 4.80 pg/ml vs. 4.68 ± 1.85 pg/ml, p < 0.05), and upregulated plasma ghrelin (0.85 ± 0.96 ng/ml vs. 2.00 ± 1.71 ng/ml, p = 0.001) but not motilin (33.08 ± 22.65 pg/ml vs. 24.12 ± 13.95 pg/ml, p > 0.05); TEA decreased sympathetic activity by 15.0% and increased vagal activity by 18.3% (both p < 0.05). CONCLUSIONS & INFERENCES: TEA at PC6 and ST36 administrated at early stage of AP reduces abdominal pain, improves GI motility, and inhibits inflammatory cytokine, TNF-α, probably mediated via the autonomic and ghrelin mechanisms.

Diterpenoids from the whole plants of Croton yunnanensis and their bioactivities.

Four new 19-nor-clerodane diterpenoids (1-4), one new 15,16-dinor-ent-pimarane diterpenoid (5) together with four known diterpenoids (6-9) were isolated from whole plants of Croton yunnanensis. The structures of these compounds were determined by extensive spectroscopic methods including 1D, 2D NMR, HR-ESI-MS, and by comparing their NMR data with those of previously reported compounds. The experimental and calculated electronic circular dichroism data were used to define their absolute configurations. The 1H and 13C NMR spectra of 6 were completely assigned for the first time. All isolated compounds (1-9) were evaluated for their cytotoxic activities against five human cancer cell lines (including SMMC-7721, HL-60, A-549, MCF-7, and SW-480), and anti-inflammatory activities in LPS-induced RAW264.7 macrophages. Crotonyunnan E (5) exhibited selective cytotoxicities against three tumor cell lines, SMMC-7721 (human hepatoma cells, IC50 4.47 ± 0.39 µM), HL-60 (human premyelocytic leukemia, IC50 14.38 ± 1.19 µM), and A-549 (human lung cancer cells, IC50 27.42 ± 0.48 µM), while none of the compounds showed obviously anti-inflammatory activities at 50 µM level.

Genus Picrasma: A comprehensive review on its ethnopharmacology, phytochemistry and bioactivities.

ETHNOPHARMACOLOGICAL RELEVANCE: The genus Picrasma belongs to the Simaroubaceae family and contains six species which are mainly distributed in tropical and subtropical regions of Asia and America. The barks, roots, stems, branches, or leaves of several Picrasma species have been applied as folk medicines to treat fever, sore throat, dysentery, eczema, nausea, loss of appetite, diabetes mellitus, cancer, and hypertension. AIM OF THE STUDY: A systematic summary on the botanic characterization, ethnopharmacological uses, phytochemistry, bioactivities and toxicity of species belonging to Picrasma was presented to facilitate the exploitation of the therapeutic potential of these plants. MATERIALS AND METHODS: The literatures about Picrasma were retrieved from a series of scientific search engines including Web of Science, SciFinder, PubMed, CNKI, Google Scholar, Elsevier, Wiley, ACS publications, and SpringerLink between 1970 and 2020. Plant names were validated by "The Plant List" (www.theplantlist.org). RESULTS: As ethnopharmacological uses, Picrasma species are valuable folk medicines to treat fever, inflammation, dysentery, eczema, cancer, diabetics, skin infection, and so on. Up to now, a total of 361 compounds including 126 alkaloids, 132 quassinoids, 67 triterpenoids, and 36 miscellaneous compounds were reported from Picrasma species. Quassinoids and alkaloids are the principal constituents in the genus. The extracts and phytochemical constituents of Picrasma species demonstrate a wide range of bioactivities including cytotoxic, anti-inflammatory, antimicrobial, and other activities. CONCLUSIONS: Picrasma species are widely used as traditional medicines, have diverse chemical constituents with obvious biological activities. Nevertheless, further studies are required on the Picrasma species to assert the ethnopharmacological uses, clarify their bioactive constituents, determine pharmacological actions, and toxicity. Therefore, the present review may provide a critical clue for future studies and further exploitations on Picrasma species.

Chiral-Selective Tamm Plasmon Polaritons.

Chiral-selective Tamm plasmon polariton (TPP) has been investigated at the interface between a cholesteric liquid crystal and a metasurface. Different from conventional TPP that occurs with distributed Bragg reflectors and metals, the chiral-achiral TPP is successfully demonstrated. The design of the metasurface as a reflective half-wave plate provides phase and polarization matching. Accordingly, a strong localized electric field and sharp resonance are observed and proven to be widely tunable.

A milbemycin compound isolated from Streptomyces Sp. FJS31-2 with cytotoxicity and reversal of cisplatin resistance activity in A549/DDP cells.

Streptomyces Sp FJS31-2 is a strain isolated from special habitat soils in the early stage of our laboratory for producing a new type of halogenated type II polyketide antibiotic with good anti-MRSA activity. In this experiment, a variety of chromatographic and spectroscopic methods was used to isolate and identify a milbemycin compound VM48130 from the ethyl acetate extract of the fermentation products. To investigate its bioactivity, Cell Counting Kit-8 (CCK-8) assay was used to test the cytotoxic activity of the compound against a variety of cancer cells (human liver cancer cell line MHCC97H and SK-Hep1, human nasopharyngeal carcinoma cell line CNE1, mouse melanoma cell line B16, human colon cancer cell line LOVO, human lung adenocarcinoma cell line A549) and normal cells (human bronchial epithelial cell line 16HBE, human normal liver cell line L02, human nasopharyngeal epithelial cell line NP69). The results showed that the compound had significant cytotoxic activity against the above cancer cells, and the IC50 values were 21.96 ± 1.45, 22.18 ± 0.55, 19.42 ± 0.71, 18.61 ± 1.68, 18.62 ± 0.67, 18.52 ± 0.64 µM, respectively. Furthermore, the CCK-8 method was used to evaluate the compound's reversal of cisplatin resistance in multidrug resistant cisplatin-resistant human lung adenocarcinoma (A549/DDP) cells. The results indicated that when the compound concentration was 0.5 µM, the reversal fold (RF) reached 6.25 and showed a dose-dependent effect. At 5 µM, the RF reached 8.35, which was approximately equivalent to the reversal effect of the positive drug verapamil at the same concentration. The expression of MDR1, MRP1, LRP, MAST1 resistance genes and the corresponding proteins were analyzed by quantitative RT-PCR and Western blot assay, and found that the compound could significantly down-regulate the expression of these genes and proteins. These results indicated that VM48130 had the potential of being a lead compound for the treatment or adjuvant treatment of cancer.

Effect of breast-conserving surgery and modified radical mastectomy on operation index, symptom checklist-90 score and prognosis in patients with early breast cancer.

The present study aims to analyze the effects of breast-conserving surgery and modified radical mastectomy on operation indexes, Symptom checklist-90 scores and prognosis in patients with early breast cancer.The clinical data of 128 patients with breast cancer who were treated in our hospital from May 2015 to May 2016 were included into the analysis. These patients were divided into 2 groups, according to the different modes of operation (n = 64): control group, patients underwent modified radical mastectomy; observation group, patients underwent early breast conserving surgery. Then, the surgical indexes and prognosis were compared between these 2 groups.Intraoperative bleeding volume, incision length and hospitalization duration were better in the observation group than in the control group (P < .05). Furthermore, postoperative symptom checklist-90 scores in the observation group were better than scores before the operation, and were better than the scores in the control group (P < .05). Moreover, the incidence of postoperative complications was lower in the observation group (3.13%) than in the control group (21.88%, P < .05).Early breast-conserving surgery is more advantageous for breast cancers and results to lesser bleeding, rapid recovery, and fewer complications.

Four new chemical constituents from Piper pleiocarpum.

Two new polyoxygenated cyclohexenes (1-2), one new benzoate derivative (3), and one new dineolignan (4) together with one known neolignan (5) were isolated from whole plants of Piper pleiocarpum. The structures of these compounds were determined by extensive spectroscopic methods including 1D, 2D NMR, HR-ESI-MS, and by comparison with the literature. The 13C NMR spectra of the known compound 5 were completely assigned for the first time. All isolated compounds (1-5) were evaluated for their cytotoxic activities against five human cancer cell lines (including A-549, SMMC-7721, HL-60, MCF-7, and SW-480), Only compound 4 showed inhibitory activity against MCF-7 cell line with IC50 value of 18.24 ± 0.69 µM.

Puupehenone, a Marine-Sponge-Derived Sesquiterpene Quinone, Potentiates the Antifungal Drug Caspofungin by Disrupting Hsp90 Activity and the Cell Wall Integrity Pathway.

The cell wall-targeting echinocandin antifungals, although potent and well tolerated, are inadequate in treating fungal infections due to their narrow spectrum of activity and their propensity to induce pathogen resistance. A promising strategy to overcome these drawbacks is to combine echinocandins with a molecule that improves their activity and also disrupts drug adaptation pathways. In this study, we show that puupehenone (PUUP), a marine-sponge-derived sesquiterpene quinone, potentiates the echinocandin drug caspofungin (CAS) in CAS-resistant fungal pathogens. We have conducted RNA sequencing (RNA-seq) analysis, followed by genetic and molecular studies, to elucidate PUUP's CAS-potentiating mechanism. We found that the combination of CAS and PUUP blocked the induction of CAS-responding genes required for the adaptation to cell wall stress through the cell wall integrity (CWI) pathway. Further analysis showed that PUUP inhibited the activation of Slt2 (Mpk1), the terminal mitogen-activated protein (MAP) kinase in this pathway. We also found that PUUP induced heat shock response genes and inhibited the activity of heat shock protein 90 (Hsp90). Molecular docking studies predicted that PUUP occupies a binding site on Hsp90 required for the interaction between Hsp90 and its cochaperone Cdc37. Thus, we show that PUUP potentiates CAS activity by a previously undescribed mechanism which involves a disruption of Hsp90 activity and the CWI pathway. Given the requirement of the Hsp90-Cdc37 complex in Slt2 activation, we suggest that inhibitors of this complex would disrupt the CWI pathway and synergize with echinocandins. Therefore, the identification of PUUP's CAS-potentiating mechanism has important implications in the development of new antifungal combination therapies.IMPORTANCE Fungal infections cause more fatalities worldwide each year than malaria or tuberculosis. Currently available antifungal drugs have various limitations, including host toxicity, narrow spectrum of activity, and pathogen resistance. Combining these drugs with small molecules that can overcome these limitations is a useful strategy for extending their clinical use. We have investigated the molecular mechanism by which a marine-derived compound potentiates the activity of the antifungal echinocandin caspofungin. Our findings revealed a mechanism, different from previously reported caspofungin potentiators, in which potentiation is achieved by the disruption of Hsp90 activity and signaling through the cell wall integrity pathway, processes that play important roles in the adaptation to caspofungin in fungal pathogens. Given the importance of stress adaptation in the development of echinocandin resistance, this work will serve as a starting point in the development of new combination therapies that will likely be more effective and less prone to pathogen resistance.

Pleiocarpumlignan A, a new dineolignan from Piper pleiocarpum Chang ex Tseng.

The investigation of chemical constituents from the whole plants Piper pleiocarpum Chang ex Tseng resulted in the isolation of one new dineolignan, pleiocarpumlignan A (1), along with one known benzoate derivative, trans-2,3-diacetoxy-1-[(benzoy1oxy)methyl]-cyclohexa-4,6-diene (2), and two known neolignans (3-4) as (±)-trans-dehydrodiisoeugenol (3), (7R,8R,3'S)-△8'-3',6'-dihydro-3'-methoxy-3,4-methylenedioxy-6'-oxo-8,3',7,O,4'-lignan (4). Their structures were elucidated through extensive spectroscopic analyses including 1D, 2D NMR, HR-ESI-MS, and by comparison with the literature. All compounds (1-4) were firstly isolated from Piper pleiocarpum Chang ex Tseng. The 13C NMR spectra of 2 were completely assigned for the first time. Cytotoxic activities of these isolated compounds against five human cancer cell lines (including A-549, SMMC-7721, HL-60, MCF-7, and SW-480) were evaluated.