UPLC-MS based metabonomics revealed the protective effects of Buyang Huanwu decoction on ischemic stroke rats.

Objective: Storke is a leading cause of death and disability affecting million people worldwide, 80% of which is ischemic stroke (IS). Recently, traditional Chinese medicines (TCMs) have received great attentions in treating IS due to their low poisonous effects and high safety. Buyang Huanwu Decoction (BHD), a famous and classical Chinese prescription, has been used for treating stroke-induced disability for centuries. Yet, its underlying mechanism is still in fancy. Methods: We first constructed an IS model by middle cerebral artery occlusion (MCAO). Then, a metabonomics study on serum samples was performed using UHPLC-QTOF/MS, followed by multivariate data analysis including principal components analysis (PCA) and orthogonal partial least squares-discriminate analysis (OPLS-DA). Results: Metabolic profiling of PCA indicated metabolic perturbation caused by MCAO was regulated by BHD back to normal levels, which is in agreement with the neurobehavioral evaluations. In the OPLS-DA, 12 metabolites were screened as potential biomarkers involved in MCAO-induced IS. Three metabolic pathways were recognized as the most relevant pathways, involving one carbon pool by folate, sphingolipid metabolism and inositol phosphate metabolism. BHD significantly reversed the abnormality of 7 metabolites to normal levels. Conclusions: This is the first study to investigate the effect of BHD on IS at the metabolite level and to reveal the underlying mechanisms of BHD, which is complementary to neurobehavioral evaluation. In a broad sense, the current study brings novel and valuable insights to evaluate efficacy of TCMs, to interpret the action mechanisms, and to provide the theoretical basis for further research on the therapeutic mechanisms in clinical practice.

Best acupuncture method for mammary gland hyperplasia: Evaluation of randomized controlled trials and Bayesian network meta-analysis.

Objective: To evaluate the effectiveness of different acupuncture treatments for mammary gland hyperplasia (MGH) using a network meta-analysis. Methods: Several databases were searched without language restrictions from 2000 to February 2023, including PubMed, Embase, Web of Science, Cochrane Library, China Science and Technology Journal Database, China Biology Medicine Database, Wanfang Database, China National Knowledge Infrastructure Database, and other professional websites and gray literature. Inclusion criteria were adult women diagnosed with MGH; intervention measures included acupuncture and related therapies; the control group was treated with simple drugs; and the research type was a randomized controlled trial (RCT). The primary outcomes were treatment effectiveness and estradiol and progesterone levels. Secondary outcomes were breast lump size and visual analog scale (VAS) score of breast pain. Exclusion criteria were studies unrelated to MGH, incorrect study populations, control measures or interventions, incomplete data, non-RCTs, case reports, and animal experiments. Cochrane tools were used to assess the risk of bias. The R software (x64 version 4.2.1), Review Manager 5.3 software and STATA 16.0 software were used for data analysis. Results: Following a rigorous screening process, data extraction, and quality assessment, 48 eligible RCTs encompassing 4,500 patients with MGH and 16 interventions were included. The results indicated that acupuncture, alone or in combination with traditional Chinese or Western medicine, had better therapeutic effects than conventional therapy. In terms of effectiveness, warm needle acupuncture was the best choice (94.6%). Bloodletting pricking was the most effective method (85.7%) for lowering progesterone levels. Bloodletting pricking was the most effective method (98.3%) for lowering estradiol levels. Manual acupuncture combined with traditional Chinese medicine was the most effective (74.5%) treatment to improve the size of the breast lump. Warm needle acupuncture was the most effective (69.8%) in improving the VAS score. Conclusion: Acupuncture therapy was more effective in treating MGH than drug therapy alone, and warm needle acupuncture and bloodletting pricking were the two best options. However, larger sample sizes and high-quality RCTs are required.

Uptake and accumulation of di(2-ethylhexyl) phthalate (DEHP) in a soil-ginseng system and toxicological mechanisms on ginseng (Panax ginseng C.A. Meyer).

Di(2-ethylhexyl) phthalate (DEHP) is regarded as a priority environmental pollutant. This study explored the adsorption and accumulation of DEHP within the ginseng-soil system and the mechanism of DEHP toxicity to ginseng (Panax ginseng C.A. Meyer). Under exposure to 22.10 mg/kg DEHP in soil, DEHP mainly accumulated in ginseng leaves (20.28 mg/kg), stems (4.84 mg/kg) and roots (2.00 mg/kg) after 42 days. The oxidative damage, metabolism, protein express of ginseng were comprehensively measured and analyzed. The results revealed that MDA presented an activation trend in ginseng stems and leaves after 42 days of DEHP exposure, while the opposite trend was observed for POD. Levels of ginsenoside metabolites Rg2, Rg3, Rg5, Rd, Rf and CK decreased in the ginseng rhizosphere exudates under DEHP stress. Further investigations revealed that DEHP disrupts ginsenoside synthesis by inducing glycosyltransferase (GS) and squalene synthase (SS) protein interactions. Molecular docking indicated that DEHP could stably bind to GS and SS by intermolecular forces. These findings provide new information on the ecotoxicological effect of DEHP on ginseng root.

American ginseng with different processing methods ameliorate immunosuppression induced by cyclophosphamide in mice via the MAPK signaling pathways.

This study aimed to clarify the effects of two processed forms of American ginseng (Panax quinquefolius L.) on immunosuppression caused by cyclophosphamide (CTX) in mice. In the CTX-induced immunosuppressive model, mice were given either steamed American ginseng (American ginseng red, AGR) or raw American ginseng (American ginseng soft branch, AGS) by intragastric administration. Serum and spleen tissues were collected, and the pathological changes in mice spleens were observed by conventional HE staining. The expression levels of cytokines were detected by ELISA, and the apoptosis of splenic cells was determined by western blotting. The results showed that AGR and AGS could relieve CTX-induced immunosuppression through the enhanced immune organ index, improved cell-mediated immune response, increased serum levels of cytokines (TNF-α, IFN-γ, and IL-2) and immunoglobulins (IgG, IgA, and IgM), as well as macrophage activities including carbon clearance and phagocytic index. AGR and AGS downregulated the expression of BAX and elevated the expression of Bcl-2, p-P38, p-JNK, and p-ERK in the spleens of CTX-injected animals. Compared to AGS, AGR significantly improved the number of CD4+CD8-T lymphocytes, the spleen index, and serum levels of IgA, IgG, TNF-α, and IFN-γ. The expression of the ERK/MAPK pathway was markedly increased. These findings support the hypothesis that AGR and AGS are effective immunomodulatory agents capable of preventing immune system hypofunction. Future research may investigate the exact mechanism to rule out any unforeseen effects of AGR and AGS.

[Effects of staged acupuncture on endometrial receptivity and anxiety in patients with recurrent implantation failure of thin endometrium based on "thoroughfare vessel is the sea of blood" theory].

OBJECTIVE: To compare the clinical efficacy between staged acupuncture based on "thoroughfare vessel is the sea of blood" theory combined with routine hormone replacement cycle treatment and routine hormone replacement cycle treatment for patients with recurrent implantation failure (RIF) of thin endometrium. METHODS: A total of 72 RIF patients with thin endometrium were randomly divided into an observation group and a control group, 36 cases in each group. The patients in the control group were treated with routine hormone replacement cycle treatment. Based on the treatment of the control group, the patients in the observation group were treated with staged acupuncture based on "thoroughfare vessel is the sea of blood" theory. The main acupoints were Neiguan (PC 6) and Gongsun (SP 4), and the supplementary acupoints were selected according to the menstrual cycle and syndrome differentiation; the acupuncture was given once every other day, 3 times a week, for 3 consecutive menstrual cycles. The thickness and shape of endometrium, and Hamilton anxiety scale (HAMA) score were observed at implantation window before and after treatment; the clinical pregnancy rate, live birth rate and cycle cancellation rate were compared between the two groups; the correlation between endometrial thickness and HAMA score was analyzed. RESULTS: Compared before treatment, the endometrial thickness in the two groups and the proportion of type A+B endometrium in the observation group were increased (P<0.05), and the HAMA scores in the two groups were decreased (P<0.05) after treatment. The above indexes in the observation group were superior to those in the control group (P<0.05). The clinical pregnancy rate and live birth rate in the observation group were higher than those in the control group (P<0.05), and the cycle cancellation rate was lower than that in the control group (P<0.05). There was a negative correlation between endometrial thickness and HAMA score (P<0.05). CONCLUSION: Based on the routine hormone replacement cycle treatment, the addition use of staged acupuncture based on "thoroughfare vessel is the sea of blood" theory could improve the thickness and shape of endometrium, relieve anxiety, increase the clinical pregnancy rate and live birth rate, and reduce the cycle cancellation rate in RIF patients with thin endometrium. The curative effect is superior to the routine hormone replacement cycle treatment alone.

Cohort difference in job environments: the mediating effect of organizational identification on the relationships between mindful leadership and self-spirituality.

This paper aims to examine the effect of mindful leadership on employees' self-spirituality, and the mediating effect of organizational identification, and the moderating effect of cohort differences in machinery companies. This study collected data from three different periods. The result demonstrated that organizational identification mediated between mindful leadership and employees' self-spirituality, which boosted to deliver the peculiarity and attractiveness of their hardworking regarding personal capability. Besides, larger cohort differences negatively moderated between mindful leadership and employees' self-spirituality, and vice versa. The main dedication is the application of critical surveys depending on important supportive elements in the associated territory.

[Detection of chondroitin sulfate in Cervi Cornu Pantotrichum and Cervi Cornu of different specifications and its application in quality evaluation].

The present study comprehensively compared the content of chondroitin sulfate in Cervi Cornu Pantotrichum(CCP) and Cervi Cornu(CC) of different specifications and explored the feasibility of chondroitin sulfate as an indicator to distinguish between CCP and CC. Twenty-two batches of CCP of different specifications(two-branched velvet antler and three-branched velvet antler) from 15 habitats, CC from 6 habitats, and 60 batches of CCP slices prepared from different parts(wax slices, powder slices, gauze slices, and bone slices) were collected. High-performance liquid chromatography(HPLC) was used to determine chondroitin sulfate content in CCP and CC of different specifications. Cluster analysis was used to classify CCP slices of different specifications. The results showed that CCP contained abundant chondroitin sulfate. The average content of chondroitin sulfate was 2.35 mg·g~(-1) in two-branched velvet antler and 1.79 mg·g~(-1) in three-branched velvet antler, significantly higher than 0.11 mg·g~(-1) in CC. Chondroitin sulfate content in wax slices, powder slices, gauze slices, and bone slices were 7.81, 8.39, 1.33, and 0.54 mg·g~(-1), respectively. Cluster analysis showed that gauze slices and bone slices could be clustered into one category and distinguished from wax slices and powder slices. CCP slices prepared from different parts could be separated well through chondroitin sulfate content. Based on the five principles of Q-marker selection, chondroitin sulfate can be used as a potential Q-marker for the identification of CCP and CC, as well as a potential quality indicator for CCP slices of different specifications(wax slices, powder slices, gauze slices, and bone slices). This research provides data support for CCP quality evaluation.

[Quality assessment of different forms of Cervi Cornu Pantotrichum based on content of free amino acids].

In this study, we analyzed the composition and content of 25 free amino acids in 32 batches of different forms of Cervi Cornu Pantotrichum(CCP; one-branched, two-branched, and three-branched) from 15 producing areas. The clustering analysis and orthogonal partial least squares discriminant analysis(OPLS-DA) were performed based on the content of 25 free amino acids. Potential differential metabolites were identified based on VIP value. The results showed that there were 25 free amino acids in CCP, and the average content of essential, non-essential, and total amino acids was 6.13, 32.99, and 39.12 mg·g~(-1), respectively. The clustering analysis and OPLS-DA demonstrated that 25 free amino acids had different content among the three forms of CCP, of which two-branched CCP samples were separately gathered into a group. Five differential components, including glutamic acid, tryptophan, ornithine, γ-aminobutyric acid, and hydroxylysine, were screened out as potential quality markers for the identification of different forms of CCP. This study provides a theoretical basis for the quality evaluation, processing, and utilization of different forms of CCP.

Sediment formation and analysis of the main chemical components of aqueous extracts from different parts of ginseng roots.

Sediment is a key issue in the production and marketing of plant beverages, as is ginseng beverages. The formation of sediment in ginseng beverages is a gradual process. This work describes the formation of sediment from different parts of ginseng and describes the color and clarity of the liquid and the amount and morphology of the sediment. The results showed there are significant differences in the sediment formation speed, morphology and transmittance for the aqueous extracts prepared from different parts of ginseng. The amounts of sediment generated from the different parts of ginseng is as follows: main root > rhizome > fibrous root. Free amino acids, Ba, Ca, Ni, and Sr concentrations are significantly and positively correlated with the transmittance. The total saponins, Al, Fe, and Mn concentrations are significantly and negatively correlated with the transmittance. There are obvious crystals and more Ca in the fibrous root sediment. We analyzed and compared the chemical components in the sediment and extract. The results show that the main components of the sediment are carbohydrates and protein. According to the partition coefficient the contents of protein, ginsenosides (Rb1, Rb2, Rb3, Rf) and some ions (Al, Fe, Ca, and Na) contribute more to the formation of the sediment than the other investigated components.

A NIR-triggered multifunctional nanoplatform mediated by Hsp70 siRNA for chemo-hypothermal photothermal synergistic therapy.

Recently, hypothermal photothermal therapy (HPTT) seemed essential for the future clinical transformation of cancer optical therapies. However, at a lower working temperature, heat shock proteins (HSPs) seriously affect the anti-tumor effect of HPTT. This work reports a reasonable design of a dual-responsive nanoplatform for the synergistic treatment of chemotherapy and HPTT. We adopted a one-step method to wrap indocyanine green (ICG) into imidazole skeleton-8 (ZIF-8) and further loaded it with the chemotherapy drug doxorubicin (DOX). Furthermore, we introduced Hsp-70 siRNA to block the affection of HSPs at an upstream node, thereby avoiding the side effects of traditional heat shock protein inhibitors. The prepared ZIF-8@ICG@DOX@siRNA nanoparticles (ZID-Si NPs) could significantly improve the stability of siRNA to effectively down-regulate the expression of HSP70 protein during the photothermal therapy, thus realizing the pH-controlled and NIR-triggered release of the chemotherapeutical drug DOX. Moreover, tumors were also imaged accurately by ICG wrapped in ZID-Si nanoparticles. After the evaluation of the in vitro and in vivo photothermal effect as well as the anti-tumor activity, we found that the added Hsp-70 siRNA enhanced the synergistic anti-cancer activity of HPTT and chemotherapy. In summary, this work holds great potential in cancer treatment, and suggests better efficacy of synergistic chemo/HPTT than the single-agent therapy.

Physiological Dose of EGCG Attenuates the Health Defects of High Dose by Regulating MEMO-1 in Caenorhabditis elegans.

EGCG, as a dietary-derived antioxidant, has been extensively studied for its beneficial health effects. Nevertheless, it induces the transient increase in ROS and leads to the hormetic extension of lifespan. How exactly biology-benefiting effects with the minimum severe adverse are realized remains unclear. Here, we showed that physiological dose of EGCG could help moderate remission in health side effects exposed to high doses, including shortened lifespan, reduced body size, decreased pharyngeal pumping rate, and dysfunctional body movement in C. elegans. Furthermore, we found this result was caused by the physiological dose of EGCG to block the continued ROS accumulation and triggered acclimation responses after stressor removal. Also, in this process, we observed that EGCG downregulated the key redox protein MEMO-1 to activate the feedback loop of NADPH oxidase-mediated redox signaling. Our data indicates that the feedback signal induced by NADPH oxidase may contribute to the health-protective mechanism of dietary polyphenols in vivo.

Consuming oxidative frying oil impairs cardiac energy production and calcium recycling, causing cardiac hypertrophy, fibrosis and diastolic dysfunction in male Sprague Dawley rats.

With regards to cardiovascular health, frequent consumption of fried foods is discouraged, despite a lack of clear evidence of a direct link between eating oxidative frying oil (OFO) and cardiovascular diseases. In this study, male Sprague Dawley rats were exposed to diets containing fresh or fried soybean oil (groups C and O, respectively) from in utero to 28 weeks of age. A subset of rats in group O was supplemented with vitamin E (500 mg/kg of DL-α-tocopherol acetate; group OE) from 8 week of age onward to mitigate oxidative stress associated with OFO ingestion. Echocardiography, cardiac histology and indices associated with ATP production and calcium cycling in cardiac tissues were measured. Compared to group C, there was cardiac hypertrophy, fibrosis and diastolic dysfunction, in groups O and OE, with no differences between the latter two groups. Although cardiac mRNA levels of genes associated with mitochondrial biogenesis and function were increased, there were lower ATP concentrations and higher transcripts of uncoupling proteins in groups O and OE than in group C. In addition, decreases in phosphorylation of phospholamban and Ca2+/calmodulin-dependent protein kinase II activity, plus increased protein phosphatase 2A activity in groups O and OE, implied calcium cycling required for cardiac function was disrupted by OFO consumption. We concluded that long-term OFO exposure resulted in cardiac hypertrophy, fibrosis and diastolic dysfunction that was not mitigated by vitamin E supplementation. Underlying mechanisms were partly attributed to inefficient energy production via uncoupled phosphorylation and disrupted calcium cycling.

[Simultaneous determination of 13 hormones in Testis et Penis Cervi using QuEChERS-ultra-high performance liquid chromatography-tandem mass spectrometry].

A reliable QuEChERS-ultra-high performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS) analysis method was developed for the simultaneous determination of 13 steroid hormones(nrolone, androstenedione, methyltestosterone, testosterone, norethindrone, medroxyprogesterone, progesterone, diethylstilbestrol, hexan-stilbestrol, estradiol, estrotriol, cortisone, hydrocortisone) in Testis et Penis Cervi. The samples were extracted with methanol and purified by QuEChERS. Subsequently, the samples were separated by ACQUITY BEH C_(18) column and detected in the multiple reaction monitoring(MRM) mode under electrospray ionization in the positive and negative ion modes, respectively. Significant differences in the content of thirteen steroid hormones in Testis et Penis Cervi between the sika deer at different periods and the red deer were observed. The content of testosterone(10.88 µg·kg~(-1)) and hydrocortisone(12.82 µg·kg~(-1)) in Testis et Penis Cervi derived from rutting sika deer was significantly higher than the content of testosterone(1.05 µg·kg~(-1)) and hydrocortisone(0.73 µg·kg~(-1)) from antler growth stage. The content of progesterone in Testis et Penis Cervi derived from red deer was 6.07 µg·kg~(-1), significantly higher than that from sika deer. The content of progesterone in the testicle of red deer reached 27.46 µg·kg~(-1), 4.5 times greater than that in the penis of red deer. The sensitivity, accuracy, and precision of the method can meet the detection requirements, and the developed method is suitable for the measurement of hormones in animal-derived food.

An antidiabetic nutraceutical combination of red yeast rice (Monascus purpureus), bitter gourd (Momordica charantia), and chromium alleviates dedifferentiation of pancreatic ß cells in db/db mice.

Antidiabetic properties of red yeast rice, bitter gourd, and chromium have gained scientific support. This study aimed to test whether a nutraceutical combination of these 3 materials prevented dedifferentiation of pancreatic ß cells. Male db/db mice (8 weeks of age) were allocated into four groups (DB, DB/L, DB/M, and DB/H; n = 8-10) and fed a high-fat diet containing 0%, 0.2%, 0.4%, or 1% nutraceutical, respectively, whereas wild-type mice receiving a standard diet served as a healthy control (C; n = 10). The nutraceutical contained 10 mg/g monacolin K, 165 µg/g chromium, and 300 mg/g bitter gourd. After 8-weeks dietary treatment, diabetic syndromes (including hyperglycemia, hyperphagia, excessive drinking, polyuria, glucosuria, albuminuria, and glucose intolerance), were improved by the nutraceutical in a dose-dependent fashion. Decreased insulin and increased glucagon in serum and pancreatic islets in db/db mice were abolished in the DB/H group. Furthermore, supplementation curtailed dedifferentiation of ß cells, as evidenced by decreasing the dedifferentiation marker (Aldh1a3) and increasing ß-cell-enriched genes and transcription factors (Ins1, Ins2, FOXO1, and NKX6.1), as well as nuclear localization of NKX6.1 in pancreatic islets when compared to the DB group. We concluded that this nutraceutical, a combination of Monascus purpureus, Momordica charantia, and chromium, could be used as an adjunct for type 2 diabetes treatment and delay disease progression by sustaining ß-cell function.

Long-term medical treatment of patients with severe burns at exposed sites.

BACKGROUND: Body parts such as the face and hands are highly exposed during daily life and burns may accumulate in these areas. In addition, residual wounds, scar hyperplasia and contracture often exist in the late stage of a deep burn in these areas, which may affect patients' appearance, movements, and mental health. However, inadequate attention has been paid to this issue which can result in problems, such as difficulty in healing, possibility of carcinoma, chronic pain and a heavy mental burden. AIM: To investigate the long-term medical treatment of patients with severe burns at exposed sites following a mass burn casualty event. METHODS: A retrospective analysis of 13 patients with severe burns at exposed sites was performed to determine their respective long-term medical treatment. A combined wound dressing scheme consisting of traditional Chinese and Western medicine was introduced to repair residual wounds. Active and passive functional exercises with massage, Chinese herbal baths and compression fixation were proposed to ameliorate the condition of the hands. A combination of physical, chemical and photoelectrical measures was adopted for anti-scar treatment. A psychological intervention and recovery guide was provided which corresponded to the patients' psychological status. RESULTS: Compared to patients who did not simultaneously receive the same treatment, patients who underwent systematic treatment recovered with a lower wound infection rate (P < 0.05), a shorter healing time (13.6 ± 3.2 d) compared with (19.1 ± 3.5 d) and more bearable pain during wound dressing at three days, one week and two weeks after a Chinese herbal bath (P < 0.05). Satisfactory results were achieved with regard to restored function of patients' joints and blood supply to nerve endings, closure of the eyelids and the size of mouth opening tended to be normal, and only 7.1% of patients were diagnosed with severe scar hyperplasia and contracture deformity compared with 30.7% in the control group. In addition, the color, thickness, vascular distribution and softness score of the scars improved (P < 0.01), and the effects of the psychological intervention was remarkable as shown by the Self-Rating Anxiety Scale and Self-Rating Depression Scale. CONCLUSION: A better prognosis can be achieved in patients in the late stage of a burn with active residual wound repair, limb functional exercise, anti-scar and psychological rehabilitation.

Dietary Exposure to Oxidized Frying Oil from Fetus to Adulthood Suppresses Male Reproductive Development by Altering Testicular Cholesterol and Testosterone Homeostasis in Sprague Dawley Rats.

BACKGROUND: Dietary frying oil may have endocrine-disrupting effects, as a feminization effect was observed in cohorts of C57BL/6J male mice fetuses from dams consuming oxidized frying oil (OFO) during pregnancy. OBJECTIVE: The aim of present study was to test the hypothesis that OFO is an anti-androgen. METHODS: In experiment 1, male progeny of Sprague Dawley female rats fed fresh oil or an OFO diet (10 g fat/100 g, from fresh or 24-h-fried soybean oil; [control diet (C) and OFO groups, respectively] from midgestation through lactation were studied. Pups were weaned at 3 wk of age and then consumed their mothers' diet until 9 wk of age. In addition, a group of dams and pups that consumed a high-fat diet (HF; 10 g fried and 20 g fresh soybean oil/100 g) was included to counteract body-weight loss associated with OFO ingestion. Indices of male reproductive development and testosterone homeostasis were measured. In experiment 2, male rats were allocated to C and OFO groups (treated as above) and indices of male fertility compared at 9-10 wk of age. RESULTS: In experiment 1, final body weights of the HF group were lower (17%) than the C group but higher (14%) than the OFO group (P < 0.0001 for each). In addition to abnormalities in seminiferous tubules, HF and OFO groups did not differ from one another, but, compared with the C group, had delayed preputial separation (4.9 d) and reductions in serum testosterone concentrations (17-74%), anogenital distance (8-20%), weights of androgen-dependent tissues (8-30%), testicular testosterone and cholesterol concentrations (30-40%), and mRNA levels of genes involved in steroidogenesis and cholesterol homeostasis (30-70%). In experiment 2, OFO-exposed males had 20% lower sperm motility (P < 0.05); however, when mated to normal females, pregnancy rates and litter sizes did not differ between OFO and C groups. CONCLUSIONS: The anti-androgenic effect of OFO in Sprague Dawley rats was attributed to decreased testicular concentrations of cholesterol (testosterone precursor) and not body-weight loss.

Discovery of novel oxoindolin derivatives as atypical dual inhibitors for DNA Gyrase and FabH.

The antibacterial agents and therapies today are facing serious problems such as drug resistance. Introducing dual inhibiting effect is a valid approach to solve this trouble and bring advantages including wide adaptability, favorable safety and superiority of combination. We started from potential DNA Gyrase inhibitory backbone isatin to develop oxoindolin derivatives as atypical dual Gyrase (major) and FabH (assistant) inhibitors via a two-round screening. Aiming at blocking both duplication (Gyrase) and survival (FabH), most of synthesized compounds indicated potency against Gyrase and some of them inferred favorable inhibitory effect on FabH. The top hit I18 suggested comparable Gyrase inhibitory activity (IC50 = 0.025 µM) and antibacterial effect with the positive control Novobiocin (IC50 = 0.040 µM). FabH inhibitory activity (IC50 = 5.20 µM) was also successfully introduced. Docking simulation hinted possible important interacted residues and binding patterns for both target proteins. Adequate Structure-Activity Relation discussions provide the future orientations of modification. With high potency, low initial toxicity and dual inhibiting strategy, advanced compounds with therapeutic methods will be developed for clinical application.

Discovery and development of novel rhodanine derivatives targeting enoyl-acyl carrier protein reductase.

A series of rhodanine derivatives RB1-RB23 were synthesized through a two-round screening. Their Mycobacterial tuberculosis (Mtb) InhA inhibitory activity and Mtb growth blocking capability were evaluated. The most potent hit compound RB23 indicated comparable InhA inhibiton (IC50 = 2.55 µM) with the positive control Triclosan (IC50 = 6.14 µM) and Isoniazid (IC50 = 8.29 µM). Its improved growth-blocking effect on Mtb and low toxicity were attractive for further development. The docking simulation revealed the possible binding pattern of this series and picked the key interacted residues as Ser20, Phe149, Lys165 and Thr196. The 3D-QSAR model visualized the SAR discussion and hinted new information. Modifying the surroundings near rhodanine moiety might be promising attempts in later investigations.

Is frying oil a dietary source of an endocrine disruptor? Anti-estrogenic effects of polar compounds from frying oil in rats.

The objective was to investigate endocrine-disrupting effects of polar compounds from oxidized frying oil. Estrogenicity of polar compounds was tested with a rat uterotrophic bioassay. Dietary oxidized frying oil (containing 51% polar compounds) or polar compounds isolated from it were incorporated into feed (in lieu of fresh soybean oil) and fed to ovariectomized rats, with or without treatment with exogenous ethynyl estradiol. Exogenous estrogen restored uterine weight, and caused histological abnormalities (stratified epithelia and conglomerate glands) as well as proliferation of uterine epithelial cells. However, tamoxifen or polar compounds reduced these effects. Furthermore, tamoxifen or polar compounds down-regulated uterine mRNA expression of estrogen receptor (ER)-target genes, implicating reduced ER activity in this hypo-uterotrophic effect. Inhibition of ER signaling and mitosis by polar compounds were attributed to reduced MAPK and AKT activation, as well as a reduced ligand binding domain-transactivity of ERα/ß. We concluded polar compounds from frying oil are potential endocrine-disrupting chemicals, with implications for food and environmental safety.

Black tea increases hypertonic stress resistance in C. elegans.

Here we identified that BTE (black tea extract), within the studied concentration range, is more effective than GTE (green tea extract) in protecting C. elegans against hypertonic stress, by enhancing survival after exposure to various salts, and alleviating suffered motility loss and body shrinkage. The mechanism of such protection may be due to the ability of black tea to induce the conserved WNK/GCK signaling pathway and down-regulation of the expression levels of nlp-29. Intriguingly, black tea does not relieve hypertonicity-induced protein damage. The findings implicate the potential health benefits of black tea consumed worldwide.