Harzianic acids and oxazolidinone from the endophytic fungus Ilyonectria sp. and their cytotoxicity activity.

Four undescribed compounds including three harzianic acids (1, 3 and 4) and one oxazolidinone (2), along with three known ones (5-7) were isolated from the solid fermented product of endophytic fungus Ilyonectria sp., their structures were elucidated as 1-amino-harzianic acid (1), ilyonectria-oxazolidinone (2),10'-nor- isoharzianic acid (3), isohomoharzianic acid (4), harzianic acid (5), isoharzianic acid (6), homoharzianic acid (7) by means of detailed chemical evidences and spectroscopic data analysis. All the compounds were evaluated for cytotoxicity against SMMC-7721 human cancer cell lines by MTS assay. Among the seven tested compounds, 1-amino-harzianic acid (1) demonstrated well cytotoxic activity against SMMC-7721 with IC50 value of 26.84 µM. The results of molecular docking indicated that compound exhibited moderate anti-tumor activity may through binding to apoptosis related proteins.

Maternal vitamin B1 is a determinant for the fate of primordial follicle formation in offspring.

The mediation of maternal-embryonic cross-talk via nutrition and metabolism impacts greatly on offspring health. However, the underlying key interfaces remain elusive. Here, we determined that maternal high-fat diet during pregnancy in mice impaired preservation of the ovarian primordial follicle pool in female offspring, which was concomitant with mitochondrial dysfunction of germ cells. Furthermore, this occurred through a reduction in maternal gut microbiota-related vitamin B1 while the defects were restored via vitamin B1 supplementation. Intriguingly, vitamin B1 promoted acetyl-CoA metabolism in offspring ovaries, contributing to histone acetylation and chromatin accessibility at the promoters of cell cycle-related genes, enhancement of mitochondrial function, and improvement of granulosa cell proliferation. In humans, vitamin B1 is downregulated in the serum of women with gestational diabetes mellitus. In this work, these findings uncover the role of the non-gamete transmission of maternal high-fat diet in influencing offspring oogenic fate. Vitamin B1 could be a promising therapeutic approach for protecting offspring health.

Polyphenolic natural products as photosensitizers for antimicrobial photodynamic therapy: recent advances and future prospects.

Antimicrobial photodynamic therapy (aPDT) has become a potent contender in the fight against microbial infections, especially in the context of the rising antibiotic resistance crisis. Recently, there has been significant interest in polyphenolic natural products as potential photosensitizers (PSs) in aPDT, given their unique chemical structures and inherent antimicrobial properties. Polyphenolic natural products, abundant and readily obtainable from natural sources, are generally regarded as safe and highly compatible with the human body. This comprehensive review focuses on the latest developments and future implications of using natural polyphenols as PSs in aPDT. Paramount polyphenolic compounds, including curcumin, hypericin, quercetin, hypocrellin, celastrol, riboflavin, resveratrol, gallic acid, and aloe emodin, are elaborated upon with respect to their structural characteristics, absorption properties, and antimicrobial effects. Furthermore, the aPDT mechanism, specifically its targeted action on microbial cells and biofilms, is also discussed. Polyphenolic natural products demonstrate immense potential as PSs in aPDT, representing a promising alternate approach to counteract antibiotic-resistant bacteria and biofilm-related infections.

Choline and trimethylamine N-oxide supplementation in normal chow diet and western diet promotes the development of atherosclerosis in Apoe -/- mice through different mechanisms.

Trimethylamine N-oxide (TMAO), a gut microbiota-dependent metabolite, has been shown to aggravate cardiovascular disease. However, the mechanisms of TMAO in the setting of cardiovascular disease progress remain unclear. Here, we aim to investigate the effects of TMAO on atherosclerosis (AS) development and the underlying mechanisms. Apoe -/- mice received choline or TMAO supplementation in a normal diet and a western diet for 12 weeks. Choline or TMAO supplementation in both normal diet and western diet significantly promoted plaque progression in Apoe-/- mice. Besides, serum lipids levels and inflammation response in the aortic root were enhanced by choline or TMAO supplementation. In particular, choline or TMAO supplementation in the western diet changed intestinal microbiota composition and bile acid metabolism. Therefore, choline or TMAO supplementation may promote AS by modulating gut microbiota in mice fed with a western diet and by other mechanisms in mice given a normal diet, even choline or TMAO supplementation in a normal diet can promote AS.

Isolation and identification of novel phenolic and lignan glycosides from Swertia davidii Franch.

Phytochemical analyses of Swertia davidii Franch. extracts using column chromatography and semi-preparative HPLC were performed. Two novel phenolic glycosides named swertiosides A and B (compounds 1 and 2, respectively) were isolated and characterized. Four known phenolic glycosides were also extracted (compounds 3-6). The structural characteristics of these novel compounds were analyzed using 1D, 2D NMR, and HRMS. All six compounds have never been isolated from this particular plant species before this study. Subsequent assessment of bioactive properties suggested that compounds 1 and 2 exhibited moderate levels of cytotoxicity.

Serum Fat-Soluble Vitamin Levels of 6,082 Minors in Zhuzhou City.

Objective: To explore the nutritional status of serum fat-soluble vitamins such as vitamin A, 25-hydroxyvitamin D, and vitamin E of minors in the Zhuzhou area to provide a scientific basis for clinical guidance to supplement fat-soluble vitamins reasonably. Method: A total of 6,082 minors who underwent physical examination from January 2017 to February 2019 in the Children's Health Department of Zhuzhou Hospital affiliated with XiangYa School of Medicine of Central South University were selected as the subjects to measure the levels of serum fat-soluble vitamins A, D, and E. Results: (1) Their average levels of serum vitamin A, 25-hydroxyvitamin D, and vitamin E were (0.34 ± 0.08) mg/mL, (34.65 ± 10.24) ng/mL, and (10.11 ± 2.65) mg/mL, respectively. (2) Serum vitamin E showed a gender difference (P < 0.001). (3) The average levels of serum 25-hydroxyvitamin D and vitamin E in infancy, early childhood, preschool age, school age, and adolescence decreased gradually (P < 0.05). In contrast, the average level of serum vitamin A ranged between 0.32 mg/mL and 0.37 mg/mL. (4) The age was negatively correlated with serum 25-hydroxyvitamin D (r = -0.517, P < 0.001) and weakly negatively correlated with vitamin E (r = -0.366, P < 0.001), but weakly positively correlated with vitamin A (r = 0.269, P < 0.001). Conclusion: Minors from infancy to adolescence in Zhuzhou should strengthen their supplementation of fat-soluble vitamins.

Near-infrared photoimmunotherapy: design and potential applications for cancer treatment and beyond.

Near-infrared photoimmunotherapy (NIR-PIT) is a newly developed cancer treatment modality based on a target-specific photosensitizer conjugate (TSPC) composed of an NIR phthalocyanine photosensitizer and an antigen-specific recognition system. NIR-PIT has predominantly been used for targeted therapy of tumors via local irradiation with NIR light, following binding of TSPC to antigen-expressing cells. Physical stress-induced membrane damage is thought to be a major mechanism underlying NIR-PIT-triggered photokilling. Notably, NIR-PIT can rapidly induce immunogenic cell death and activate the adaptive immune response, thereby enabling its combination with immune checkpoint inhibitors. Furthermore, NIR-PIT-triggered "super-enhanced permeability and retention" effects can enhance drug delivery into tumors. Supported by its potential efficacy and safety, NIR-PIT is a rapidly developing therapeutic option for various cancers. Hence, this review seeks to provide an update on the (i) broad range of target molecules suitable for NIR-PIT, (ii) various types of receptor-selective ligands for designing the TSPC "magic bullet," (iii) NIR light parameters, and (iv) strategies for enhancing the efficacy of NIR-PIT. Moreover, we review the potential application of NIR-PIT, including the specific design and efficacy in 19 different cancer types, and its clinical studies. Finally, we summarize possible NIR-PIT applications in noncancerous conditions, including infection, pain, itching, metabolic disease, autoimmune disease, and tissue engineering.

Regulation of wakefulness by astrocytes in the lateral hypothalamus.

The lateral hypothalamus (LH) is an important brain region mediating sleep-wake behavior. Recent evidence has shown that astrocytes in central nervous system modulate the activity of adjacent neurons and participate in several physiological functions. However, the role of LH astrocytes in sleep-wake regulation remains unclear. Here, using synchronous recording of electroencephalogram/electromyogram in mice and calcium signals in LH astrocytes, we show that the activity of LH astrocytes is significantly increased during non-rapid eye movement (NREM) sleep-to-wake transitions and decreased during Wake-to-NREM sleep transitions. Chemogenetic activation of LH astrocytes potently promotes wakefulness and maintains long-term arousal, while chemogenetic inhibition of LH astrocytes decreases the total amount of wakefulness in mice. Moreover, by combining chemogenetics with fiber photometry, we show that activation of LH astrocytes significantly increases the calcium signals of adjacent neurons, especially among GABAergic neurons. Taken together, our results clearly illustrate that LH astrocytes are a key neural substrate regulating wakefulness and encode this behavior through surrounding GABAergic neurons. Our findings raise the possibility that overactivity of LH astrocytes may be an underlying mechanism of clinical sleep disorders.

Uncovering the molecular mechanism of Gynostemma pentaphyllum (Thunb.) Makino against breast cancer using network pharmacology and molecular docking.

Because of their strong anti-cancer efficacy with fewer side effects, traditional Chinese medicines (TCM) have attracted considerable attention for their potential application in treating breast cancer (BC). However, knowledge about the underlying systematic mechanisms is scarce. Gynostemma pentaphyllum (Thunb.) Makino (GP), a creeping herb, has been regularly used as a TCM to prevent and treat tumors including BC. Again, mechanisms underlying its anti-BC properties have remained elusive. We used network pharmacology and molecular docking to explore the mechanistic details of GP against BC. The TCM systems pharmacology database and analysis platform and PharmMapper Server database were used to retrieve the chemical constituents and potential targets in GP. In addition, targets related to BC were identified using DrugBank and Therapeutic Target Database. Protein-protein interaction network, Gene Ontology, and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses of crucial targets were performed using the Search Tool for the Retrieval of Interacting Genes/Proteins and database for annotation, visualization, and integrated discovery databases, whereas the network visualization analysis was performed using Cytoscape 3.8.2. In addition, the molecular docking technique was used to validate network pharmacology-based predictions. A comparison of the predicted targets of GP with those of BC-related drugs revealed 26 potential key targets related to the treatment of BC, among which ALB, EGFR, ESR1, AR, PGR, and HSP90AA1 were considered the major potential targets. Finally, network pharmacology-based prediction results were preliminarily verified by molecular docking experiments. In addition, chemical constituents and potential target proteins were scored, followed by a comparison with the ligands of the protein. We provide a network of pharmacology-based molecular mechanistic insights on the therapeutic action of GP against BC. We believe that our data will serve as a basis to conduct future studies and promote the clinical applications of GP.

[New method for green extraction of ginsenosides based on mechanochemically-assisted extraction and deep eutectic solvents].

Ginsenosides are the main active ingredients in ginseng. Studies have shown that ginsenosides have anti-virus, anti-tumor, anti-aging, nootropic, cardiovascular diseases-protecting, and other pharmacological activities. Thus, the development and utilization of ginsenosides have persistently attracted much attention. At present, the extraction of ginsenosides is mainly based on organic solvents, and there are relatively few studies on their green extraction. In this study, different deep eutectic solvents(DESs) were synthesized by heating and stirring method, combined with an emerging technology, mechanochemically-assisted extraction(MCAE), to extract ginsenosides in a green way. Six parameters that might affect the extraction effect were optimized to determine the optimal conditions, and the method validation was conducted. The new established method was compared with a commonly used extraction method(ultrasound-assisted extraction using 70% ethanol) to evaluate its extraction efficiency. The results revealed that the optimal extraction conditions of DES-MCAE were that the volume ratio of DES3(choline chloride∶urea 1∶2) and water in the extraction solvent was 6∶4, and the liquid ratio and the linear vibration speed were 0.05 g·mL~(-1) and 4.0 m·s~(-1); the extraction was performed twice, 40 s each. With only 80 s extraction, the extraction rate of this method was 36.22% higher than that of ultrasoun-dassisted extraction using 70% ethanol. In this study, a DESs-based pretreatment method for ginsenosides was established and its rapid, green and efficient extraction was realized, which provided new ideas and methods for further research on green extraction of other active ingredients from Chinese medicine.

Chlorogenic acid, a natural product as potential inhibitor of COVID-19: virtual screening experiment based on network pharmacology and molecular docking.

Chlorogenic acid (CGA) is a potential inhibitor of Coronavirus Disease 2019 (COVID-19). ACE2 and its co-expressed proteins are SARS-CoV-2 receptors, which have been linked to SARS-CoV-2 infection and considered as the key target of SARS-CoV-2 in entering target cells. Here, network pharmacology was used to investigate the mechanism by which CGA affected COVID-19. A total of 70 potential targets related to the treatment of COVID-19 were obtained, among which NFE2L2, PPARG, ESR1, ACE, IL6, and HMOX1 might be the main potential targets. Finally, CGA and potential target proteins were scored by molecular docking, and the prediction results of network pharmacology were preliminarily verified. Moreover, CGA had potential anti-SARS-CoV-2 activity via integrating three common receptors in clinical practice compared with clinical trial drugs registered for the treatment of COVID-19, as shown by molecular docking. The mechanism of CGA against COVID-19 was initially investigated using network pharmacology, followed by molecular docking.

Guidelines on the treatment with integrated traditional Chinese medicine and western medicine for severe coronavirus disease 2019.

Severe Coronavirus Disease 2019 (COVID-19) is characterized by numerous complications, complex disease, and high mortality, making its treatment a top priority in the treatment of COVID-19. Integrated traditional Chinese medicine (TCM) and western medicine played an important role in the prevention, treatment, and rehabilitation of COVID-19 during the epidemic. However, currently there are no evidence-based guidelines for the integrated treatment of severe COVID-19 with TCM and western medicine. Therefore, it is important to develop an evidence-based guideline on the treatment of severe COVID-19 with integrated TCM and western medicine, in order to provide clinical guidance and decision basis for healthcare professionals, public health personnel, and scientific researchers involved in the diagnosis, treatment, and care of COVID-19 patients. We developed and completed the guideline by referring to the standardization process of the "WHO handbook for guideline development", the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system, and the Reporting Items for Practice Guidelines in Healthcare (RIGHT).

Dahuang Zhechong Pills Suppress Silicosis Fibrosis Progression via p38 MAPK/TGF-ß1/Smad Pathway In Vitro.

BACKGROUND: Dahuang Zhechong pills (DHZCP) is a classic Chinese medicinal prescription in "Treatise on Cold Pathogenic and Miscellaneous Diseases (Shanghan Zabing Lun)," and it has the function of tonifying blood, nourishing Yin, and removing blood stasis. Previous studies have shown that DHZCP could alleviate SiO2 induced pulmonary fibrosis in mice. This study aims to further explore the preventive and therapeutic effects of DHZCP against silicosis fibrosis and the underlying mechanisms in vitro. METHODS: We used the experimental model of SiO2-induced MH-S cells to evaluate the therapeutic potential of DHZCP. MH-S cells induced by SiO2 were intervened with the drug-containing serum of DHZCP, and the effects of drug-containing serum of DHZCP on the MH-S cells were detected by CCK8, ELISA, flow cytometry, western blot, and immunofluorescence. RESULTS: DHZCP improved cell viability by reducing apoptosis. It also decreased the levels of TNF-α, IL-1ß, IL-6 in the supernatant of MH-S cells induced by SiO2, inhibited the expression of p38 MAPK, blocked the activation of NF-κB, and controlled the upstream inflammatory response by multiple targeting. Concomitantly, we observed upregulation of Smad7 and a marked decline in TGF-ß1, α-SMA, Smad2, Smad3 expression in MH-S cells treated with DHZCP. CONCLUSION: To sum up, we conclude that DHZCP protects against SiO2-induced silicosis by reducing the persistent irritation of inflammation, regulating the p38 MAPK/TGF-ß1/Smad pathway.

Effects of phosphorus fertilizer on root characteristics, uptake and utilization of phosphorus and yield of dryland wheat with contrasting yearly rainfall pattern.

To understand the growth responses of dryland wheat to different application rates of phosphorus fertilizer in different rainfall years, we examined root characteristics, spike number, yield and phosphate utilization. Results would help improve phosphate fertilizer use in dryland wheat production. We carried out a field experiment at the research station of Shanxi Agricultural University from 2012 to 2016. We examined the effects of four application rates of phosphorus (0, 75, 150 and 225 kg·hm-2 on root growth, phosphate utilization and yield formation of dryland wheat in different years with contrasting rainfall pattern. Compared with the treatment without phosphorus fertilization, phosphate application increased root surface area at all growth stages and root weight density in the 0-80 cm soil layer at jointing, anthesis, and maturity stages. Phosphate application significantly increased soil water consumption from jointing to anthesis, and total soil water consumption in the growing season. Phosphate application enhanced the amount of pre-anthesis phosphate translocation and phosphate accumulation of grain. Spike number, yield and water use efficiency were increased with 75, 150 and 225 kg P·hm-2 by 9.2% to 22.5%, 11.8% to 30.0%, and 2.1% to 12.1%, respectively. In the dry years, the application rates of 150 and 225 kg P·hm-2 in comparison to 75 kg P·hm-2 significantly increased root weight density and root surface area at all stages, soil water consumption from sowing to jointing and from jointing to anthesis, and total water consumption in the growing season. In comparison to the rate of 75 kg P·hm-2, 150 and 225 kg P·hm-2 increased soil water consumption from sowing to jointing by 7.3-8.7 mm, soil water consumption from jointing to anthesis by 15.6-18.1 mm, and total water consumption by 15.6-18.1 mm. Significant increase in the pre-anthesis phosphate translocation and phosphate accumulation in grain was higher under 150 and 225 kg P·hm-2 than that under 75 kg P·hm-2 in dry years. Furthermore, the two rates (150 and 225 kg P·hm-2) in dry years increased spike number by 9.3%-10.7% and yield by 11.9%-14.6%. The application rate of 150 kg P·hm-2 significantly improved phosphorus use efficiency by 20%-82% in comparison to other rates. In normal years, the rates of 150 and 225 kg P·hm-2 increased root surface area, root weight density at both anthesis and maturity compared with 75 kg P·hm-2. Soil water consumption from anthesis to maturity and total soil water consumption in the growing season were also increased by 1.2-15.0 and 3.8-23.1 mm, respectively. In addition, phosphorus accumulation in post-anthesis and phosphate accumulation in grain were increased in both 150 and 225 kg P·hm-2, which increased spike number by 1.4%-9.6% and yield by 3.5%-10.4%. The effects of phosphate application at the rate of 150 kg P·hm-2 were significantly different from 75 and 225 kg P·hm-2. In conclusion, phosphorus fertilizer application enhanced uptake of water and phosphate in dryland wheat at early and middle growth stages in dry years and at the late growth stage in normal years. Phosphorus application increased wheat yield mainly due to the increases of spike number. The application of 150 kg P·hm-2 is the best choice for high water and phosphorus fertilizer use efficiency and high yield in both dry and normal years.

Citrus flavonoids and the intestinal barrier: Interactions and effects.

The intestinal barrier plays a central role in sustaining gut homeostasis and, when dysfunctional, may contribute to diseases. Dietary flavonoids derived from Citrus genus represent one of the main naturally occurring phytochemicals with multiple potential benefits for the intestinal barrier function. In the intestine, citrus flavonoids (CFs) undergo ingestion from the lumen, biotransformation in the epithelial cells and/or crosstalk with luminal microbiota to afford various metabolites that may in turn exert protective actions on gut barrier along with their parental compounds. Specifically, the health-promoting properties of CFs and their metabolic bioactives for the intestinal barrier include their capacity to (a) modulate barrier permeability; (b) protect mucus layer; (c) regulate intestinal immune system; (d) fight against oxidative stress; and (e) positively shape microbiome and metabolome. Notably, local effects of CFs can also generate systemic benefits, for instance, improvement of gut microbial dysbiosis helpful to orchestrate gut homeostasis and leading to alleviation of systemic dysmetabolism. Given the important role of the intestinal barrier in overall health, further understanding of underlying action mechanisms and ultimate health effects of CFs as well as their metabolites on the intestine is of great significance to future application of citrus plants and their bioactives as dietary supplements and/or functional ingredients in medical foods.

Excessive ROS production and enhanced autophagy contribute to myocardial injury induced by branched-chain amino acids: Roles for the AMPK-ULK1 signaling pathway and α7nAChR.

BACKGROUNDS AND AIMS: Leucine, isoleucine, and valine are diet derived and essential amino acids that are termed branched-chain amino acids (BCAA). BCAA are widely used as dietary supplements to boost muscle growth and enhance exercise performance. However, the effects of BCAA on myocardial function are largely unknown. This study was designed to investigate whether BCAA affect heart function and, if so, to further explore the underlying molecular basis for the observed effects. METHODS AND RESULTS: C57BL/6J mice were randomly divided into two groups, the control group received solvent (water) and the BCAA group received 2% BCAA dissolved in water, for a successive period of 12 weeks. Compared with control, BCAA treatment significantly increased water consumption without changing body weight or diet consumption; heart tissue BCAA levels were increased, markers representative of myocardial injury in heart tissue including c-reactive protein and cardiac muscle troponin were increased ; and creatine kinase, creatine kinase-MB, and lactate dehydrogenase were increased in serum; severe myocardial fibrosis was observed by Masson staining, which was accompanied by increased reactive oxygen species (ROS) production and decreased superoxide dismutase activity in heart tissue; both p-AMPK and p-ULK1 were significantly increased as was autophagy, judged by the presence of LC3 by western blotting and immunofluorescence, increased numbers of autophagosomes were found by transmission electron microscopy in the BCAA group. In vitro, 20 mmol/L BCAA significantly decreased cell viability and increased the production of ROS, as well as the expression of p-AMPK/AMPK and p-ULK1/ULK1 in cultured H9C2 cells. Treatment with the ROS scavenger N-acetyl-L-cysteine (NAC) improved cell viability and reversed ROS changes. Decreased H9C2 cell viability induced with 20 mmol/L BCAA was reversed by either blocking AMPK or inhibition of ULK1. Furthermore, blocking AMPK significantly decreased p-ULK1/ULK1, while inhibition of ULK1 reversed the enhanced expression of LC3-II/LC3-I induced by BCAA. Excessive ROS production and decreased cell viability induced by BCAA were further confirmed in primary cultured murine cardiomyocytes. Pharmacological activation of α7nAChR with PNU-282987 attenuated BCAA-induced injury in primary murine cardiomyocytes. However, this compound failed to suppress BCAA activation of AMPK and autophagy (LC3-II/I ratio). CONCLUSION: These results provide the first evidence that treatment of mice with BCAA induced myocardial injury by triggering excessive ROS production and by enhancing AMPK-ULK1 pathway-dependent autophagy. These findings suggested that inhibition of either ROS production or autophagy may alleviate myocardial injury induced by BCAA.

Role of fecal calprotectin in the diagnosis of neonatal necrotizing enterocolitis: a Meta analysis / 中国当代儿科杂志

OBJECTIVE@#To study the value of fecal calprotectin (FC) in the diagnosis of neonatal necrotizing enterocolitis (NEC) through a Meta analysis.@*METHODS@#Web of Science, Cochrane Library, PubMed, Embase, China National Knowledge Infrastructure, Weipu Periodical Database, Wanfang Data, Chinese Biomedical Literature Database were searched for related studies published up to May 2020, with manual search as supplementation. The QUADAS criteria were used to evaluate the quality of the articles included. Meta-DiSc 1.4 and Stata 15.0 software were used to perform the Meta analysis, including the evaluation of specificity, sensitivity, likelihood ratio, and diagnostic odds ratio. The sensitivity analysis and heterogeneity testing were performed, and the summary receiver operating characteristic (SROC) curve and Fagan diagram were plotted.@*RESULTS@#A total of 15 articles were enrolled, involving 1 719 neonates. Among these articles, 4 had low quality, 2 had high quality, and the rest had medium quality. There was high heterogeneity between studies, and there was no threshold effect or publication bias. The random effects model analysis showed that FC had a pooled specificity of 0.80 (95%@*CONCLUSIONS@#FC has high potential and efficiency in the early diagnosis of NEC. FC measurement can be used for the diagnosis of NEC, but it should be combined with clinical manifestations and other related laboratory examinations.

Pterocephanoside A, a new iridoid from a traditional Tibetan medicine, Pterocephalus hookeri.

This work obtained and identified pterocephanoside A (1), one new iridoid glucoside derivative with rare structure of three iridoid glycosides linked to cyclopenta[c]pyran-3(1H)-one, and 10 known iridoids (2-11) from Pterocephalus hookeri through silica gel column chromatography and semi-preparative HPLC. The structure of the new compound was confirmed by 1D and 2D NMR and HRMS data analysis. Compounds 1 and 2 were isolated from this plant for the first time. The iridoids mostly possessed seco-iridoid subtype and iridoid subtype skeletons from P. hookeri. Compounds 1, 3, 4, and 6-11 showed weak anti-inflammatory activity.

Selective Photokilling of Colorectal Tumors by Near-Infrared Photoimmunotherapy with a GPA33-Targeted Single-Chain Antibody Variable Fragment Conjugate.

Antibody-based near-infrared photoimmunotherapy (NIR-PIT) is an attractive strategy for cancer treatment. Tumor cells can be selectively and efficiently killed by the targeted delivery of an antibody-photoabsorber complex followed by exposure to NIR light. Glycoprotein A33 antigen (GPA33) is highly expressed in most human colorectal cancers (CRCs) and is an ideal diagnostic and therapeutic target. We previously produced a single-chain fragment of a variable antibody against GPA33 (A33scFv antibody). Here, we investigate the efficacy of NIR-PIT by combining A33scFv with the NIR photoabsorber IR700 (A33scFv-IR700). In vitro, recombinant A33scFv displayed specific binding and delivery of an NIR dye to GPA33-positive tumor cells. Furthermore, A33scFv-IR700-mediated NIR-PIT was successful in rapidly and specifically killing GPA33-positive colorectal tumor cells. NIR-PIT treatment induced the release of lactate dehydrogenase from tumor cells, followed by cell necrosis, rather than apoptosis, through the promotion of reactive oxygen species accumulation in tumor cells. In mice bearing LS174T tumor grafts, A33scFv selectively accumulated in GPA33-positive tumors. Following only a single injection of the conjugate and subsequent illumination, A33scFv-IR700-mediated NIR-PIT induced a significant increase in therapeutic response in LS174T-tumor mice compared with that in the non-NIR-PIT groups (p < 0.001). Because the GPA33 antigen is specifically expressed in CRC tumors, A33scFv-IR700 might be a promising antibody fragment-photoabsorber conjugate for NIR-PIT of CRC.