Litchi pulp-derived gamma-aminobutyric acid (GABA) extract counteracts liver inflammation induced by litchi thaumatin-like protein.

Gamma-aminobutyric acid (GABA) is the predominant amino acid in litchi pulp, known for its neuroregulatory effects and anti-inflammatory properties. Although previous research has highlighted the pro-inflammatory characteristics of litchi thaumatin-like protein (LcTLP), interplay between GABA and LcTLP in relation to inflammation remains unclear. This study aims to explore the hepatoprotective effects of the litchi pulp-derived GABA extract (LGE) against LcTLP-induced liver inflammation in mice and LO2 cells. In vivo experiments demonstrated that LGE significantly reduced the levels of aspartate transaminase and alanine transaminase, and protected the liver against infiltration of CD4+ and CD8+ T cells and histological injury induced by LcTLP. Pro-inflammatory cytokines including interleukin-6, interleukin-1ß, and tumor necrosis factor-α were also diminished by LGE. The LGE appeared to modulate the mitogen-activated protein kinase (MAPK) signaling pathway to exert its anti-inflammatory effects, as evidenced by a reduction of 47%, 35%, and 31% in phosphorylated p38, JNK, and ERK expressions, respectively, in the liver of the high-dose LGE group. Additionally, LGE effectively improved the translocation of gut microbiota by modulating its microbiological composition and abundance. In vitro studies have shown that LGE effectively counteracts the increase in reactive oxygen species, calcium ions, and pro-inflammatory cytokines induced by LcTLP. These findings may offer new perspectives on the health benefits and safety of litchi consumption.

[Highly polar chemical constituents from whole herb of Scindapsus officinalis].

Macroporous resin column chromatography, MCI medium pressure column chromatography, and semi-preparative high performance liquid chromatography were employed to isolate the chemical components from the aqueous extract of the whole herb of Scindapsus officinalis. The structures of the compounds were identified based on the physical and chemical properties and the spectroscopic data. Ten compounds were isolated from the aqueous extract and identified as 3,4-dihydroxyphenylethyl-8-O-[ß-D-apiofuranosyl-(1→4)]-ß-D-glucopyranoside(1), alternamide B(2), 3,4-dihydroxyphenylethyl-O-ß-D-glucopyranoside(3), 1-(4-hydroxy)-phenylethyl-ß-D-galactopyranoside(4), 3,4-dihydroxyphenylethyl-8-O-[ß-D-apiofuranosyl-(1→2)]-ß-D-glucopyranoside(5), hydroxytyrosol-4-O-ß-D-glucopyranoside(6), 3,5-dihydroxyphenylethyl-3-O-ß-D-glucopyranoside(7), salidroside(8), dihydroisoquinolone(9), and 4-methoxybenzenepropanol-3-O-ß-D-glucopyranoside(10). Among them, compound 1 was a new one, and compounds 2-10 were obtained from S. officinalis for the first time. The RAW264.7 cells were exposed to lipopolysaccharide for the mode-ling of inflammation, and the cells were then used to examine anti-inflammatory activities of the compounds. The results showed that compounds 6 and 7 had strong anti-inflammatory activities, while compounds 1, 2, and 5 had moderate anti-inflammatory activities.

The History of Controlling and Treating Infectious Diseases in Ancient China.

Infectious diseases are the common enemies of mankind. In the course of historical development, they persistently threaten human health and safety. Even today, despite the developments in medical science, we cannot escape the fear and suffering caused by infectious diseases. Whether in ancient or modern times, the source of infection, route of transmission, and a susceptible population are the three key conditions for the prevalence and spread of infectious diseases. All factors closely related to these three conditions can affect the prevalence of infectious diseases. China is one of the cradles of world civilization. The ancient people accumulated a great deal of experience and lessons in the long struggle against infectious diseases. In the face of the current threat posed by widespread infectious disease, it is imperative to review and summarize ancient Chinese ideas and health policies on epidemic prevention and control to inspire contemporary efforts in the prevention and control of infectious disease. The combination of prevention-oriented epidemic prevention ideology and traditional medicine provides valuable insights, especially for impoverished and medically underserved regions.

Efficient discovery of active isolates from Dioscorea spongiosa by the combination of bioassay-guided macroporous resin column chromatography and high-speed counter-current chromatography.

In the present study, twelve compounds from Dioscorea spongiosa were successfully purified by an efficient technique combined bioassay-guided fractionation macroporous resin column chromatography (MRCC) pretreatment and high-speed counter-current chromatography (HSCCC) separation for the first time. Then, D101 MRCC was used to fractionate the crude extract into five parts, which further applied the bioassay-guided fractionation strategy to screen the active fractions of 2 and 4. As for the separation, 200 mg Fr.2 was purified by HSCCC using EtOAc/n-BuOH/H2 O (2:2:3, v/v), leading to annulatomarin (1), dioscoresides C (2), diosniponol C (3), methyl protodioscin (4), pseudoprotodioscin (5), protogracillin (6), as well as 200 mg Fr.4 yielding montroumarin (7), dioscorone A (8), diosniponol D (9), protodioscin (10), gracillin (11), and dioscin (12) using CH2 Cl2 /MeOH/H2 O (3:3:2, v/v) with the purities over 95.0%. Finally, the isolates were assayed for their anti-inflammatory, urico-lowering, and anti-diabetic activities in vitro, which indicated that the steroidal saponins of 5, 6, and 11 showed all these three activities.

Synthesis and anti-HIV activities of phorbol derivatives.

In this study, 37 derivatives of phorbol esters were synthesized and their anti-HIV-1 activities evaluated, building upon our previous synthesis of 51 phorbol derivatives. 12-Para-electron-acceptor-trans-cinnamoyl-13-decanoyl phorbol derivatives stood out, demonstrating remarkable anti-HIV-1 activities and inhibitory effects on syncytia formation. These derivatives exhibited a higher safety index compared with the positive control drug. Among them, 12-(trans-4-fluorocinnamoyl)-13-decanoyl phorbol, designated as compound 3c, exhibited the most potent anti-HIV-1 activity (EC50 2.9 nmol·L-1, CC50/EC50 11 117.24) and significantly inhibited the formation of syncytium (EC50 7.0 nmol·L-1, CC50/EC50 4891.43). Moreover, compound 3c is hypothesized to act both as an HIV-1 entry inhibitor and as an HIV-1 reverse transcriptase inhibitor. Isothermal titration calorimetry and molecular docking studies indicated that compound 3c may also function as a natural activator of protein kinase C (PKC). Therefore, compound 3c emerges as a potential candidate for developing new anti-HIV drugs.

Optimization of ultrasonic-assisted supramolecular solvent microextraction of coumarins from Cortex fraxini using response surface methodology combined with artificial neural network-genetic algorithm.

A simple, fast, and efficient ultrasonic-assisted supramolecular solvent microextraction combined with high performance liquid chromatography method was developed for the determination of coumarins in Cortex fraxini, including esculin, esculetin and fraxetin. In this study, a novel supramolecular solvent was prepared with 1-octanol, tetrahydrofuran and water for the first time, and its composition, viscosity, density, structure, and micromorphology were characterized. The prepared supramolecular solvent exhibited vesicular structures and had the characteristics of low viscosity. Through single-factor experiments, response surface methodology and artificial neural network-genetic algorithm, the optimal extraction conditions were obtained as follows: NaCl concentration of 1 mol mL-1, pH value of 10, solid-liquid ratio of 10:1, vortex time of 30 s, ultrasonic power of 100 W, ultrasonic temperature of 60 °C, ultrasonic time of 15 min, centrifugation speed of 5000 rpm, and centrifugation time of 1 min. The results demonstrated that the artificial neural network model exhibited maximum R-values of 0.98703, 0.97440, 0.99836, and 0.95447 for training, testing, validation, and all dataset, respectively. The minimum mean square errors were 0.75, 10.15, 1.99, and 2.63, respectively. This indicated that the predicted values were almost consistent with the actual values. Under the optimal conditions, the total extraction yields of target analytes reached 2.80 %. The calibration curves for each analyte exhibited excellent linearity within the linear range (r > 0.9993). The limits of detection and quantification ranged from 4.87 to 6.55 ng mL-1 and 16.24 to 21.84 ng mL-1, respectively. The recoveries ranged from 98.71 % to 111.01 % with relative standard deviations of less than 3.6 %. The present method had the advantages of short extraction time (15 min) and less solvent consumption (0.5 mL). The prepared supramolecular solvent was proved to have great potential in extracting coumarins from medicinal plants.

The selection landscape and genetic legacy of ancient Eurasians.

The Holocene (beginning around 12,000 years ago) encompassed some of the most significant changes in human evolution, with far-reaching consequences for the dietary, physical and mental health of present-day populations. Using a dataset of more than 1,600 imputed ancient genomes1, we modelled the selection landscape during the transition from hunting and gathering, to farming and pastoralism across West Eurasia. We identify key selection signals related to metabolism, including that selection at the FADS cluster began earlier than previously reported and that selection near the LCT locus predates the emergence of the lactase persistence allele by thousands of years. We also find strong selection in the HLA region, possibly due to increased exposure to pathogens during the Bronze Age. Using ancient individuals to infer local ancestry tracts in over 400,000 samples from the UK Biobank, we identify widespread differences in the distribution of Mesolithic, Neolithic and Bronze Age ancestries across Eurasia. By calculating ancestry-specific polygenic risk scores, we show that height differences between Northern and Southern Europe are associated with differential Steppe ancestry, rather than selection, and that risk alleles for mood-related phenotypes are enriched for Neolithic farmer ancestry, whereas risk alleles for diabetes and Alzheimer's disease are enriched for Western hunter-gatherer ancestry. Our results indicate that ancient selection and migration were large contributors to the distribution of phenotypic diversity in present-day Europeans.

Correlations between the structure and anti-diabetic activity of novel polysaccharides from raw and "Nine Steaming Nine Sun-Drying" Polygonti rhizome.

"Nine Steaming Nine Sun-Drying" Polygonti rhizome has been used as valuable tonic health-care products for thousands of years. This research aimed to determine the correlations between the structure and anti-diabetic activities of three novel polysaccharides isolated from the raw and "Nine Steaming Nine Sun-Drying" Polygonti rhizome, with PRP-R from the raw ones and PRP-9Z and PRP-9A from the steamed ones. Structures of the isolated polysaccharides were determined by IR and NMR spectra, as well as monosaccharide composition and methylation analysis. In vitro assays indicated that PRP-9Z could improve the glucose consumptions more effectively than PRP-R and PRP-9A via Akt/GSK3ß insulin signal pathway by western blotting analysis. In vivo assays indicated PRP-9Z could improve the glucose tolerance in the BKS-db mice. Histopathological assay demonstrated that PRP-9Z effectively reduced the damage of the kidney and liver. The above results indicated that PRP-9Z from "Nine Steaming Nine Sun-Drying" Polygonti rhizome showed significant anti-diabetic properties, which indicated that PRP-9Z with higher content of →1)-ß-Frup-(2→ was more active than PRP-R with higher →1,6)-ß-Fruf-(2→ and PRP-9A with higher →4)-ß-Galp(1→.

Selenium in the treatment of mild-to-moderate Graves' orbitopathy: a 5-year prospective controlled cohort study.

PURPOSE: Graves' orbitopathy (GO) is the main extrathyroidal manifestation of Graves' disease. However, limited studies have investigated the actual efficacy of selenium in GO therapy. This longitudinal study explored the effect of selenium on QOL and prognosis of patients with mild-to-moderate GO. METHODS: We conducted a 5-year prospective controlled cohort clinical trial to determine the effect of selenium on 74 patients with mild-to-moderate GO. Patients received selenium yeast or placebo orally for 6 months and were followed up at 6 months and at 5 years by biochemical examination, ophthalmologist evaluation and QOL questionnaire to assess oculopathy and QOL. RESULTS: (1) During a follow-up period of 3-6 months, in the selenium group, the symptoms of tearing, grittiness and conjunctival congestion improved (P < 0.01); clinical activity scores and total GO-QOL scores increased relative to baseline (P < 0.01); TRAb was decreased at the 6-month evaluation (P = 0.003); and patients treated with selenium had a higher rate of improvement and a lower rate of worsening than patients treated with placebo (P < 0.05). (2) Exploratory evaluations at 6 months after drug withdrawal confirmed the earlier results; further changes included alleviation of blurred vision and double vision symptoms in the selenium group (P < 0.01). (3) At the 5-year follow-up, compared with baseline, proptosis, clinical activity scores, TRAb level and total GO-QOL scores in both the selenium and placebo groups were significantly improved (P < 0.01). CONCLUSION: Six months of selenium supplementation may effectively change the early course of mild-to-moderate GO, but this regimen makes no difference in long-term outcomes.

Secondary metabolites from Scindapsus officinalis (Roxb.) Schott. with in vitro antidiabetic activities.

One new phenolic cyclobutantetraol ester united chromone glycoside (1), one new amide (2), and three new phenyl ethanol glycosides (3-5) were obtained from the water extract of Scindapsus officinalis (Roxb.) Schott, in which compound 1 was the first reported structure incorporating the phenolic cyclobutantetraol ester and chromone via the glucose phenolic metabolites in nature. Structures of the isolated compounds, including absolute configurations, were elucidated according to the analysis of HRESIMS, NMR, ECD and BLYP/6-31G* geometry optimization calculations of 13C NMR data. All isolates (1-5) were evaluated for the antidiabetic activity by the insulin resistance (IR) model and anti-inflammatory activity against NO production in vitro. Compounds 1-3 showed strong antidiabetic activities, greatly promoting the glucose consumption in the insulin resistance HepG2 cells compared with the model group, however, 1-5 showed weak anti-inflammatory activities.

Saltiness enhancement by "má là" umami flavor in NaCl model aqueous and oil-added systems.

The health concerns associated with high dietary sodium and the quest for a sensory experience have prompted the need for new strategies that can reduce the salt content of foods and have good acceptability. To investigate the cross-modal interaction effects of "má là" umami flavor (total of eight carriers) on the saltiness perception and effective sodium reduction in low-to-strong NaCl aqueous solutions (0.203 %-1.39 %) and oil-added systems (5 %, 10 %, 15 %, 20 %, 25 % canola oil, wt%), sixteen assessors were selected and two methods including saltiness intensity comparison with a category scale and rating with a generalized Labeled Magnitude Scale (gLMS) were used. The results showed PnSnUn carriers significantly enhance saltiness at moderate-to-strong NaCl solutions, and higher saltiness intensity with the addition of canola oil, especially at 25 % oil level. In addition, based on the developed Stevens' power function the sodium reduction was calculated, it was evident that two "má là" umami flavor combinations (one flavor combination was low "má", low "là" and moderate umami, and the other flavor combination with moderate "má", low "là" and moderate umami) were found to perform best with maximum sodium reduction of 18.88 % and 18 %, respectively, and when incorporating 25 % canola oil, the maximum sodium reduction raised by approximately 10 % (to 28.00 % and 28.42 %). This research not only confirmed the positive modulating effect of the "má là" umami flavor on saltiness perception in NaCl solutions, but also showed that the presence of oil further enhanced this effect. This work offered a new and promising insight into the development of foods with reduced sodium content while maintaining the saltiness properties.

[Combination of acupuncture and medication for dry eye complicated with computer vision syndrome: a randomized controlled trial].

OBJECTIVE: To compare the clinical efficacy of acupuncture, Chinese medication and combination of acupuncture and medication in the treatment of dry eye complicated with computer vision syndrome (CVS). METHODS: A total of 152 patients with dry eye complicated with CVS were randomly divided into an acupuncture-medication group (38 cases, 1 case was removed), an acupuncture group (38 cases, 1 case dropped off), a Chinese medication group (38 cases, 1 case was removed), and a western medication group (38 cases, 1 case dropped off). In the western medication group, sodium hyaluronate eye drop combined with esculin and digitalis glycosides eye drop were used. In the acupuncture group, acupuncture was applied at bilateral Taiyang (EX-HN 5)， Cuanzhu (BL 2), Fengchi (GB 20), Qimen (LR 14) , and Hegu (LI 4) etc., once a day. In the Chinese medication group, Yiqi Congming decoction formula ganule was given orally, one dose a day. In the acupuncture-medication group, acupuncture combined with Yiqi Congming decoction formula granule were used. All groups were treated for 14 d. The non-invasive first tear film break-up time (NIBUT f), non-invasive average tear film break-up time (NIBUT av), tear meniscus height (TMH), ocular surface disease index (OSDI) score, and CVS symptom score were compared between the patients of each group before and after treatment. RESULTS: After treatment, the NIBUT f, NIBUT av, and TMH were increased compared with those before treatment in the patients of the 4 groups (P<0.01); the NIBUT f and NIBUT av in the acupuncture-medication group and the acupuncture group were higher than those in the Chinese medication group and the western medication group (P<0.05), and the TMH in the acupuncture-medication group and the Chinese medication group were higher than those in the acupuncture group and the western medication group (P<0.05). After treatment, the OSDI scores, the various scores and total scores of CVS (except for head symptom score in the western medication group) were decreased compared with those before treatment in the patients of the 4 groups (P<0.01). The OSDI score, total score, eye symptom score, and body symptom score of CVS in the acupuncture-medication group were lower than those in the acupuncture group, the Chinese medication group, and the western medication group (P<0.01, P<0.05), the head symptom score of the acupuncture-medication group was lower than that in the western medication group (P<0.05), and the CVS physical symptom scores and mental cognitive symptom scores of the acupuncture-medication group and the acupuncture group were lower than those in the Chinese medication group and the western medication group (P<0.05). CONCLUSION: Acupuncture has advantages in improving NIBUT f, NIBUT av, and CVS physical symptoms and cognitive symptoms, and the Chinese medication has advantage in improving TMH. The combination of acupuncture and Chinese medication has better effects compared with monotherapy.

Notopterol Inhibits the NF-κB Pathway and Activates the PI3K/Akt/Nrf2 Pathway in Periodontal Tissue.

Notopterol, an active component isolated from the traditional Chinese medicine Notopterygium incisum Ting ex H.T. Chang, exerts anti-inflammatory activity in rheumatoid arthritis. However, its roles in suppression of inflammatory insults and halting progression of tissue destruction in periodontitis remain elusive. In this study, we reveal that notopterol can inhibit osteoclastogenesis, thereby limiting alveolar bone loss in vivo. In vitro results demonstrated that notopterol administration inhibited synthesis of inflammatory mediators such as IL-1ß, IL-32, and IL-8 in LPS-stimulated human gingival fibroblasts. Mechanistically, notopterol inhibits activation of the NF-κB signaling pathway, which is considered a prototypical proinflammatory signaling pathway. RNA sequencing data revealed that notopterol activates the PI3K/protein kinase B (Akt)/NF-E2-related factor 2 (Nrf2) signaling pathway in LPS-stimulated human gingival fibroblasts, a phenomenon validated via Western blot assay. Additionally, notopterol treatment suppressed reactive oxygen species levels by upregulating the expression of antioxidant genes, including heme oxygenase 1 (HO-1), NAD(P)H quinone oxidoreductase 1 (NQO1), catalase (CAT), and glutathione reductase (GSR), indicating that notopterol confers protection against oxidative stress. Notably, inhibition of Akt activity by the potent inhibitor, MK-2206, partially attenuated both anti-inflammatory and antioxidant effects of notopterol. Collectively, these results raise the possibility that notopterol relieves periodontal inflammation by suppressing and activating the NF-κB and PI3K/AKT/Nrf2 signaling pathways in periodontal tissue, respectively, suggesting its potential as an efficacious treatment therapy for periodontitis.

Complete chloroplast genome of Adonis pseudoamurensis W.T.Wang (Ranunculaceae).

Adonis pseudoamurensis W.T. Wang 1980 is an important traditional medicinal plant used for the treatment of cardiac diseases. The complete chloroplast (cp) genome of Adonis pseudoamurensis is reported for the first time in this study. The circular cp genome is 156,917 bp in length, consisting of a large single-copy region (86,262 bp), a small single-copy region (18,067 bp), and two inverted repeat regions (26,294 bp). The genome encodes 129 genes, comprising 84 protein-coding genes, 37 transfer RNA (tRNA) genes, and 8 ribosomal RNA (rRNA) genes. Phylogenetic analysis showed that A. pseudoamurensis is closely related to A. amurensis.

Weizmannia coagulans JA845 improves atherosclerosis induced by vitamin D3 and high-fat diet in rats through modulating lipid metabolism, oxidative stress, and endothelial vascular injury.

AIMS: Probiotics have been proved to be strongly linked to the occurrence and progression of atherosclerosis. This study aimed to investigate the improved effects and mechanisms underlying a potential probiotic, Weizmannia coagulans JA845, on atherosclerosis. METHODS AND RESULTS: Male Sprague-Dawley rats supported on a high-fat diet with vitamin D3 supplementation were subjected to W. coagulans JA845 treatment. W. coagulans JA845 obviously alleviated histological abnormalities of the abdominal aorta. After 6 weeks of W. coagulans JA845 administration, levels of TG, TC, LDL, ox-LDL, ROS, and MDA in the JA845 group decreased significantly, and those of HDL, GSH-Px, and SOD were markedly elevated. Treatment with W. coagulans JA845 also inhibited the secretion of ICAM-1 and VCAM-1 and regulated the plasma NO and eNOS content. In brief, administration of W. coagulans JA845 promoted the expression of the SIRT3/SOD2/FOXO3A pathway, inhibited the lipid metabolism pathway, SREBP-1c/FAS/DGAT2, and suppressed the JNK2/P38 MAPK/VEGF pathway implicated in endothelial injury. CONCLUSIONS: These results indicated W. coagulans JA845 improved atherosclerosis by regulating lipid metabolism, antioxidative stress, and protecting against endothelial injury.

Composition, functional properties, health benefits and applications of oilseed proteins: A systematic review.

Common oilseeds, such as soybean, peanut, rapeseed, sunflower seed, sesame seed and chia seed, are key sources of edible vegetable oils. Their defatted meals are excellent natural sources of plant proteins that can meet consumers' demand for health and sustainable substitutes for animal proteins. Oilseed proteins and their derived peptides are also associated with many health benefits, including weight loss and reduced risks of diabetes, hypertension, metabolic syndrome and cardiovascular events. This review summarizes the current status of knowledge on the protein and amino acid composition of common oilseeds as well as the functional properties, nutrition, health benefits and food applications of oilseed protein. Currently, oilseeds are widely applied in the food industry regarding for their health benefits and good functional properties. However, most oilseed proteins are incomplete proteins and their functional properties are not promising compared to animal proteins. They are also limited in the food industry due to their off-flavor, allergenic and antinutritional factors. These properties can be improved by protein modification. Therefore, in order to make better use of oilseed proteins, methods for improving their nutrition value, bioactive activity, functional and sensory characteristics, as well as the strategies for reducing their allergenicity were also discussed in this paper. Finally, examples for the application of oilseed proteins in the food industry are presented. Limitations and future perspectives for developing oilseed proteins as food ingredients are also pointed out. This review aims to foster thinking and generate novel ideas for future research. It will also provide novel ideas and broad prospects for the application of oilseeds in the food industry.

Photodynamic Therapy, Probiotics, Acetic Acid, and Essential Oil in the Treatment of Chronic Wounds Infected with Pseudomonas aeruginosa.

As a prevalent medical problem that burdens millions of patients across the world, chronic wounds pose a challenge to the healthcare system. These wounds, often existing as a comorbidity, are vulnerable to infections. Consequently, infections hinder the healing process and complicate clinical management and treatment. While antibiotic drugs remain a popular treatment for infected chronic wounds, the recent rise of antibiotic-resistant strains has hastened the need for alternative treatments. Future impacts of chronic wounds are likely to increase with aging populations and growing obesity rates. With the need for more effective novel treatments, promising research into various wound therapies has seen an increased demand. This review summarizes photodynamic therapy, probiotics, acetic acid, and essential oil studies as developing antibiotic-free treatments for chronic wounds infected with Pseudomonas aeruginosa. Clinicians may find this review informative by gaining a better understanding of the state of current research into various antibiotic-free treatments. Furthermore. this review provides clinical significance, as clinicians may seek to implement photodynamic therapy, probiotics, acetic acid, or essential oils into their own practice.

Trophic status and lake depth play important roles in determining the nutrient-chlorophyll a relationship: Evidence from thousands of lakes globally.

A fundamental problem in lake eutrophication management is that the nutrient-chlorophyll a (Chl a) relationship shows high variability due to diverse influences of for example lake depth, lake trophic status, and latitude. To accommodate the variability induced by spatial heterogeneity, a reliable and general insight into the nutrient-Chl a relationship may be achieved by applying probabilistic methods to analyze data compiled across a broad spatial scale. Here, the roles of two critical factors determining the nutrient-Chl a relationship, lake depth and trophic status, were explored by applying Bayesian networks (BNs) and a Bayesian hierarchical linear regression model (BHM) to a compiled global dataset from 2849 lakes and 25083 observations. We categorized the lakes into three groups (shallow, transitional, and deep) according to mean and maximum depth relative to mixing depth. We found that despite a stronger effect of total phosphorus (TP) and total nitrogen (TN) on Chl a when combined, TP played a dominant role in determining Chl a, regardless of lake depth. However, when the lake was hypereutrophic and/or TP was >40 µg/L, TN had a greater impact on Chl a, especially in shallow lakes. The response curve of Chl a to TP and TN varied with lake depth, with deep lakes having the lowest yield Chl a per unit of nutrient, followed by transitional lakes, while shallow lakes had the highest ratio. Moreover, we found a decrease of TN/TP with increasing Chl a concentrations and lake depth (represented as mixing depth/mean depth). Our established BHM may help estimating lake type and/or lake-specific acceptable TN and TP concentrations that comply with target Chl a concentrations with higher certainty than can be obtained when bulking all lake types.

Say 'No' to Cancer and 'Yes' to Cranberry: The Role of Cranberry Extract in Inhibition of Growth of Lung Adenocarcinoma Cells.

BACKGROUND/AIM: Lung cancer is the leading cause of mortality due to cancer death. Treatment of lung adenocarcinoma (LUAD) is still challenging. Cranberries contain many rich bioactive components that may help fight cancer. The action of cranberry against some cancer types has been reported, however, its role in lung cancer has only been investigated in large-cell lung cancer. In this study, we expanded current research on the role of cranberry in LUAD. MATERIALS AND METHODS: A549 LUAD cancer cells were treated with commercial cranberry extract (CE). Proliferation of A549 cells was measured with a clonogenic survival assay and quick proliferation assay. Caspase-3 activity was used to evaluate apoptosis of A549 cells. Reverse transcriptase-polymerase chain reaction was conducted to investigate the possible molecular mechanisms involved in the action of CE. RESULTS: Treatment of LUAD with CE reduced the percentage of A549 colonies. This was consistent with the decrease in the optic density of cancer cells after treatment with CE. Caspase-3 activity increased after treatment with CE. The anti-proliferative effect of CE on A549 cells correlated with reduced expression of pro-proliferation molecules cyclin E, cyclin-dependent kinase 2 (CDK2) and CDK4. The pro-apoptotic effect of CE on A549 cells correlated with the reduced expression of the anti-apoptotic molecule caspase 8 and FADD-like apoptosis regulator (FLIP). CONCLUSION: CE had an inhibitory effect on the growth of LUAD cells by modulation of both pro-proliferative and anti-apoptotic molecules. Our research hopes to guide future treatment options for LUAD.

Synthesis and Biological Evaluation of Gentiopicroside Derivatives as Novel Cyclooxygenase-2 Inhibitors with Anti-Inflammatory Activity.

Purpose: Nonsteroidal anti-inflammatory drugs cause a series of adverse reactions. Thus, the search for new cyclooxygenase-2 selective inhibitors have become the main direction of research on anti-inflammatory drugs. Gentiopicroside is a novel selective inhibitor of cyclooxygenase-2 from Chinese herbal medicine. However, it is highly hydrophilic owing to the presence of the sugar fragment in its structure that reduces its oral bioavailability and limits efficacy. This study aimed to design and synthesize novel cyclooxygenase-2 inhibitors by modifying gentiopicroside structure and reducing its polarity. Materials and Methods: We introduced hydrophobic acyl chloride into the gentiopicroside structure to reduce its hydrophilicity and obtained some new derivatives. Their in vitro anti-inflammatory activities were evaluated against NO, TNF-α, PGE2, and IL-6 production in the mouse macrophage cell line RAW264.7 stimulated by lipopolysaccharide. The in vivo inhibitory activities were further tested against xylene-induced mouse ear swelling. Molecular docking predicted that whether new compounds could effectively bind to target protein cyclooxygenase-2. The inhibitory activity of new compounds to cyclooxygenase-2 enzyme were verified by the in vitro experiment. Results: A total of 21 novel derivatives were synthesized, and exhibit lower polarities than the gentiopicroside. Most compounds have good in vitro anti-inflammatory activity. The in vivo activity results demonstrated that 8 compounds were more active than gentiopicroside. The inhibition rate of some compounds was higher than celecoxib. Molecular docking predicted that 6 compounds could bind to cyclooxygenase-2 and had high docking scores in accordance with their potency of the anti-inflammatory activity. The confirmatory experiment proved that these 6 compounds had significant inhibitory effect against cyclooxygenase-2 enzyme. Structure-activity relationship analysis presumed that the para-substitution with the electron-withdrawing groups may benefit the anti-inflammatory activity. Conclusion: These gentiopicroside derivatives especially PL-2, PL-7 and PL-8 may represent a novel class of cyclooxygenase-2 inhibitors and could thus be developed as new anti-inflammatory agents.