The optimal exercise parameters of Tai Chi on the effect of glucose and lipid metabolism in patients with type 2 diabetes mellitus: A meta-analysis.

OBJECTIVES: To explore the optimal exercise parameters of Tai Chi for improving glucose and lipid metabolism in type 2 diabetes mellitus (T2DM) patients. METHODS: This meta-analysis was conducted in accordance with the reporting guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Six databases were retrieved, with retrieval dates ranging from the establishment of the databases to December 2022. Data extraction and study quality assessment were independently performed by two researchers according to the Physical Therapy Evidence Database (PEDro) scale. The effects of different Tai Chi exercise parameters on glucose and lipid metabolism in T2DM patients were analyzed by subgroup analyses and meta-regressions. RESULTS: A total of sixteen randomized controlled trials were included in the meta-analysis. The results indicated that Tai Chi had a significant and moderate impact on fasting blood glucose in T2DM patients, as well as a significant and large impact on glycosylated hemoglobin. Tai Chi had a significant and moderate impact on triglyceride, and a small, non-significant improvement on total cholesterol. The intervention frequency and duration of a single session were identified as predictors of the impact of Tai Chi on triglyceride. The optimal exercise parameters identified were the 24-style simplified Tai Chi, with a recommended exercise duration of 45-60 min per session, performed 5-7 times per week, and continued for at least 4-7 weeks. CONCLUSIONS: Tai Chi can significantly improve the glucose and lipid metabolism in T2DM patients, and the 24-style simplified Tai Chi with high exercise frequency and short duration may be the optimal exercise parameter for enhancing glucose and lipid metabolism. PROSPERO: Registration number: CRD42023395282.

The floodplain inundation history of the Murray-Darling Basin through two-monthly maximum water depth maps.

With growing concerns over water management in rivers worldwide, researchers are seeking innovative solutions to monitor and understand changing flood patterns. In a noteworthy advancement, stakeholders interested in the changing flood patterns of the Murray Darling Basin (MDB) in Australia, covering an area of 1 million km2, can now access a consistent timeseries of water depth maps for the entire basin. The dataset covers the period from 1988 to 2022 at two-monthly timestep and was developed using remotely sensed imagery and a flood depth estimation model at a spatial resolution of ≈30 m, providing a comprehensive picture of maximum observed inundation depth across the MDB. Validation against 13 hydrodynamic model outputs for different parts of the MDB yielded a mean absolute error of 0.49 m, demonstrating reasonable accuracy and reliability of the dataset. The resulting dataset is best suited to system-wide analysis but might also be useful for those interested in the history of flooding at specific locations in the system. We provide the dataset, visualization tools, and examples to support ongoing research.

Chlorogenic acid delays the progression of Parkinson's disease via autophagy induction in Caenorhabditis elegans.

OBJECTIVES: Parkinson's disease (PD) is the second most common neurodegenerative disease. Chlorogenic acid (CGA) is a polyphenolic substance derived from various medicinal plants. Although CGA is reported to have potential anti-PD effect, the beneficial effect and the underlying mechanism remain unclear. In this study, we aimed to further investigate the protective effect and clarify the mechanism of action of CGA in Caenorhabditis elegans (C. elegans) models of PD. METHODS: Measurements of a-synuclein aggregation, movement disorders, and lipid, ROS and malondialdehyde (MDA) contents were observed in NL5901 nematodes. Determinations of dopamine (DA) neuron degeneration, food perception, and ROS content were performed in 6-OHDA-exposed BZ555 nematodes. The autophagy activation of CGA was monitored using DA2123 and BC12921 nematodes. Meanwhile, RNAi technology was employed to knockdown the autophagy-related genes and investigate whether the anti-PD effect of CGA was associated with autophagy induction in C. elegans. RESULTS: CGA significantly reduced α-synuclein aggregation, improved motor disorders, restored lipid content, and decreased ROS and MDA contents in NL5901 nematodes. Meanwhile, CGA inhibited DA neuron-degeneration and improved food-sensing behavior in 6-OHDA-exposed BZ555 nematodes. In addition, CGA increased the number of GFP::LGG-1 foci in DA2123 nematodes and degraded p62 protein in BC12921 nematodes. Meanwhile, CGA up-regulated the expression of autophagy-related genes in NL5901 nematodes. Moreover, the anti-PD effect of CGA was closely related to autophagy induction via increasing the expression of autophagy-related genes, including unc-51, bec-1, vps-34, and lgg-1. CONCLUSIONS: The present study indicates that CGA exerts neuroprotective effect in C. elegans via autophagy induction.

Development of tracheotrocar cuff filling device and application effect in hyperbaric oxygen therapy for patients with tracheotomy cannula / 中国实用护理杂志

Objective:To design a tracheotomy cannula cuff filling device for hyperbaric oxygen therapy, which is convenient for clinical operation, improves work efficiency and reduces the incidence of aspiration pneumonia.Methods:This study was a randomized controlled trial. From July 2020 to June 2022, 90 patients with tracheotomy who were treated with hyperbaric oxygen in the First Hospital of Jiaxing were selected as the research objects. According to the random number table method, the patients were divided into the experimental group and the control group, with 45 cases in each group. In the experimental group, the cuff pressure was maintained by the tracheotomy cannula cuff filling device, and in the control group, the traditional water injection method was used to maintain the cuff pressure. The operation time, infection index and incidence of aspiration pneumonia were compared between the two groups.Results:The operation time in the experimental group was (6.33 ± 1.31) s lower than that in the control group (40.96 ± 3.70) s, and the difference was statistically significant ( t=-59.11, P<0.05). Body temperature, C-reactive protein and procalcitonin after treatment in the experimental group were (36.91 ± 0.83) ℃, (34.59 ± 16.25) mg/L, (1.57 ± 0.82) μg/L, respectively, lower than those in the control group (37.42 ± 0.72) ℃, (44.18 ± 18.10) mg/L, (2.45 ± 0.92) μg/L, the differences were statistically significant ( t=-3.09, -2.64, -4.73, all P<0.05). The difference of white blood cell count post-treatment between the two groups was not statistically significant ( P>0.05). The incidence of aspiration pneumonia in the experimental group was 11.11%(5/45) lower than 31.11%(14/45) in the control group, and the difference was statistically significant ( χ2=5.17, P<0.05). Conclusions:The application of tracheotomy cannula cuff filling device can simplify the operation process, reduce the incidence of infection and aspiration pneumonia, and optimize the clinical work.

Characterization of Roasting Time on Sensory Quality, Color, Taste, and Nonvolatile Compounds of Yuan An Yellow Tea.

Roasting is crucial for producing Yuan An yellow tea (YAYT) as it substantially affects sensory quality. However, the effect of roasting time on YAYT flavor quality is not clear. To investigate the effect of roasting time on the sensory qualities, chemical components, odor profiles, and metabolic profile of YAYTs produced with 13 min roasting, 16 min roasting, 19 min roasting, 22 min roasting, and 25 min roasting were determined. The YAYTs roasted for 22 min got higher sensory scores and better chemical qualities, such as the content of gallocatechin (GC), gallocatechin gallate (GCG), free amino acids, solutable sugar, meanwhile the lightness decreased, the hue of tea brew color (b) increased, which meant the tea brew got darker and yellower. YAYTs roasted for 22 min also increased the contents of key odorants, such as benzaldehyde, nonanal, ß-cyclocitral, linalool, nerol, α-cedrol, ß-ionone, limonene, 2-methylfuran, indole, and longiborneol. Moreover, non-targeted metabolomics identified up to 14 differentially expressed metabolites through pair-wise comparisons, such as flavonoids, phenolic acids, sucrose, and critical metabolites, which were the main components corresponding to YAYT roasted for 22 min. In summary, the current results provide scientific guidance for the production of high quality YAYT.

Antibiotic resistance modifying ability of phytoextracts in anthrax biological agent Bacillus anthracis and emerging superbugs: a review of synergistic mechanisms.

BACKGROUND AND OBJECTIVES: The chemotherapeutic management of infections has become challenging due to the global emergence of antibiotic resistant pathogenic bacteria. The recent expansion of studies on plant-derived natural products has lead to the discovery of a plethora of phytochemicals with the potential to combat bacterial drug resistance via various mechanisms of action. This review paper summarizes the primary antibiotic resistance mechanisms of bacteria and also discusses the antibiotic-potentiating ability of phytoextracts and various classes of isolated phytochemicals in reversing antibiotic resistance in anthrax agent Bacillus anthracis and emerging superbug bacteria. METHODS: Growth inhibitory indices and fractional inhibitory concentration index were applied to evaluate the in vitro synergistic activity of phytoextract-antibiotic combinations in general. FINDINGS: A number of studies have indicated that plant-derived natural compounds are capable of significantly reducing the minimum inhibitory concentration of standard antibiotics by altering drug-resistance mechanisms of B. anthracis and other superbug infection causing bacteria. Phytochemical compounds allicin, oleanolic acid, epigallocatechin gallate and curcumin and Jatropha curcas extracts were exceptional synergistic potentiators of various standard antibiotics. CONCLUSION: Considering these facts, phytochemicals represents a valuable and novel source of bioactive compounds with potent antibiotic synergism to modulate bacterial drug-resistance.

Metabolomics Provides A Novel Interpretation of the Changes in Main Compounds during Black Tea Processing through Different Drying Methods.

This study aimed to compare the effect of hot roller (HR) drying and hot air (HA) drying on the sensory evaluation, chemical quality, antioxidant activity, and metabolic profile of Yihong Congou black tea processed from E'cha NO1. The Yihong Congou black tea dried with HA obtained higher sensory scores and better chemical qualities such as the hue of tea brew color (a and b), content of theaflavins, thearubigins, water extract, free amino acids, tea polyphenol, and the ratio of polyphenol to amino acids as well as higher antioxidant capacities compared to that dried with HR. The HA drying tea increased the contents of volatile compounds that had positive correlation with sweet and flowery flavor, while the HR drying tea increased the contents of volatile compounds related to fruity flavor. Moreover, non-targeted metabolomics data indicated that the levels of most free amino acids significantly increased, while the levels of most soluble sugars reduced in the HA drying method compared to the HR drying method. The metabolic analysis was also consistent with the above results and revealed that D-ribose and gallic acid were the main characteristic metabolites of HA drying. Our results could provide a technical reference and theoretical guide to processing a high quality of Yihong Congou black tea.

Lychee seed polyphenol protects the blood-brain barrier through inhibiting Aß(25-35)-induced NLRP3 inflammasome activation via the AMPK/mTOR/ULK1-mediated autophagy in bEnd.3 cells and APP/PS1 mice.

Blood-brain barrier (BBB) dysfunction has been implicated in Alzheimer's disease (AD) and is closely linked to the release of proinflammatory cytokines in brain capillary endothelial cells. We have previously reported that lychee seed polyphenols (LSP) exerted anti-neuroinflammatory effect. In this study, we aimed to explore the protective effect of LSP on BBB integrity. The monolayer permeability of bEnd.3 cells, and the mRNA level and protein expression of tight junction proteins (TJs), including Claudin 5, Occludin, and ZO-1, were examined. In addition, the inhibition of Aß(25-35)-induced NLRP3 inflammasome activation, and the autophagy induced by LSP were investigated by detecting the expression of NLRP3, caspase-1, ASC, LC3, AMPK, mTOR, and ULK1. Furthermore, the cognitive function and the expression of TJs, NLRP3, caspase-1, IL-1ß, and p62 were determined in APP/PS1 mice. The results showed that LSP significantly decreased the monolayer permeability and inhibited the NLRP3 inflammasome in Aß(25-35)-induced bEnd3 cells. In addition, LSP induced autophagy via the AMPK/mTOR/ULK1 pathway in bEnd.3 cells, and improved the spatial learning and memory function, increased the TJs expression, and inhibited the expression of NLRP3, caspase-1, IL-1ß, and p62 in APP/PS1 mice. Therefore, LSP protects BBB integrity in AD through inhibiting Aß(25-35)-induced NLRP3 inflammasome activation via the AMPK/mTOR/ULK1-mediated autophagy.

[Moxibustion therapy in prevention and treatment of coronavirus disease 2019 (COVID-19): construction and application of non-contact diagnosis and treatment mode].

OBJECTIVE: To establish and promote the non-contact doctor-patient interactive diagnosis and treatment mode based on mobile internet for the treatment of coronavirus disease 2019 (COVID-19) with moxibustion therapy, and to observe the feasibility and effectiveness of the model in the pandemic. METHODS: A total of 43 first-line medical staff and 149 suspected and confirmed cases with COVID-19 [18 cases in medical observation period, 17 cases of mild type (cold dampness and stagnation in the lung), 24 cases of ordinary type (cold-dampness accumulated in the lung) and 90 cases in recovery period (qi deficiency of spleen and lung)] were included. A non-contact doctor-patient interactive diagnosis and treatment platform was established for the treatment of COVID-19 with indirect moxibustion plaster based on mobile internet. By the platform, the patients were instructed to use indirect moxibustion plaster in treatment. For the first-line medical staff and patients in the medical observation period, Zusanli (ST 36), Qihai (CV 6) and Zhongwan (CV 12) were selected. For the mild cases (cold dampness and stagnation in the lung) and the cases of ordinary type (cold-dampness accumulated in the lung), Hegu (LI 4), Taichong (LR 3), Zusanli (ST 36) and Guanyuan (CV 4) were selected. In the recovery period (qi deficiency of spleen and lung), Dazhui (GV 14), Feishu (BL 13), Geshu (BL 17), Zusanli (ST 36) and Kongzui (LU 6) were used. The treatment was given once daily for 40 min each time. The intervention lasted for 10 days. After intervention, the infection rate and the improvement in the symptoms and psychological status of COVID-19 were observed in clinical first-line medical staff and COVID-19 patients. RESULTS: In 10 days of intervention with indirect moxibustion plaster, there was "zero" infection among medical staff. Of 43 first-line physicians and nurses, 33 cases had some physical symptoms and psychological discomforts, mainly as low back pain, poor sleep and anxiety. After treatment, regarding the improvements in the symptoms and psychological discomforts, the effective rate was 78.8% (26/33) and the curative rate was 36.4% (12/33). Regarding the improvements in psychological discomforts, the effective rate was 58.3% (14/24) and the curative rate was 37.5 (9/24). Of 149 patients, 133 cases had the symptoms and psychological discomforts. After treatment, regarding the improvements in the symptoms and psychological discomforts, the effective rate was 81.2% (108/133) and the curative rate was 34.6% (46/133). Regarding the improvements in psychological discomforts, the effective rate was 76.5% (52/68) and the curative rate was 57.4 % (39/68). CONCLUSION: It is feasible to apply the indirect moxibustion plaster technique based on mobile internet to the treatment COVID-19. This mode not only relieves the symptoms such as cough and fatigue, improves psychological state, but also possibly prevents the first-line medical staff from COVID-19.

Polyphenols isolated from lychee seed inhibit Alzheimer's disease-associated Tau through improving insulin resistance via the IRS-1/PI3K/Akt/GSK-3ß pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Lychee seed, the seed of Litchi chinensis Sonn. is one of the commonly used in traditional Chinese medicine (TCM). It possesses many pharmacological effects such as blood glucose and lipid-lowering effects, liver protection, and antioxidation. Our preliminary studies have proven that an active fraction derived from lychee seed (LSF) can significantly decrease the blood glucose level, inhibit amyloid-ß (Aß) fibril formation and Tau hyperphosphorylation, and improve the cognitive function and behavior of Alzheimer's disease (AD) model rats. AIM OF THE STUDY: The aim of this study was to identify the main active components in LSF that can inhibit the hyperphosphorylation of Tau through improving insulin resistance (IR) in dexamethasone (DXM)-induced HepG2 and HT22 cells. MATERIALS AND METHODS: The isolation was guided by the bioactivity evaluation of the improvement effect of IR in HepG2 and HT22 cells. The mRNA and protein expressions of IRS-1, PI3K, Akt, GSK-3ß, and Tau were measured by RT-PCR, Western blotting, and immunofluorescence methods, respectively. RESULTS: After extraction, isolation, and elucidation using chromatography and spectrum technologies, three polyphenols including catechin, procyanidin A1 and procyanidin A2 were identified from fractions 3, 5, and 9 derived from LSF. These polyphenols inhibit hyperphosphorylated Tau via the up-regulation of IRS-1/PI3K/Akt and down-regulation of GSK-3ß. Molecular docking result further demonstrate that these polyphenols exhibit good binding property with insulin receptor. CONCLUSIONS: catechin, procyanidin A1, and procyanidin A2 are the main components in LSF that inhibit Tau hyperphosphorylation through improving IR via the IRS-1/PI3K/Akt/GSK-3ß pathway. Therefore, the findings in the current study provide novel insight into the anti-AD mechanism of the components in LSF derived from lychee seed, which is valuable for the further development of a novel drug or nutrient supplement for the prevention and treatment of AD.

Polyphyllin VI Induces Caspase-1-Mediated Pyroptosis via the Induction of ROS/NF-κB/NLRP3/GSDMD Signal Axis in Non-Small Cell Lung Cancer.

Trillium tschonoskii Maxim (TTM), a traditional Chinese medicine, has been demonstrated to have a potent anti-tumor effect. Recently, polyphyllin VI (PPVI), a main saponin isolated from TTM, was reported by us to significantly suppress the proliferation of non-small cell lung cancer (NSCLC) via the induction of apoptosis and autophagy in vitro and in vivo. In this study, we further found that the NLRP3 inflammasome was activated in PPVI administrated A549-bearing athymic nude mice. As is known to us, pyroptosis is an inflammatory form of caspase-1-dependent programmed cell death that plays an important role in cancer. By using A549 and H1299 cells, the in vitro effect and action mechanism by which PPVI induces activation of the NLRP3 inflammasome in NSCLC were investigated. The anti-proliferative effect of PPVI in A549 and H1299 cells was firstly measured and validated by MTT assay. The activation of the NLRP3 inflammasome was detected by using Hoechst33324/PI staining, flow cytometry analysis and real-time live cell imaging methods. We found that PPVI significantly increased the percentage of cells with PI signal in A549 and H1299, and the dynamic change in cell morphology and the process of cell death of A549 cells indicated that PPVI induced an apoptosis-to-pyroptosis switch, and, ultimately, lytic cell death. In addition, belnacasan (VX-765), an inhibitor of caspase-1, could remarkably decrease the pyroptotic cell death of PPVI-treated A549 and H1299 cells. Moreover, by detecting the expression of NLRP3, ASC, caspase-1, IL-1ß, IL-18 and GSDMD in A549 and h1299 cells using Western blotting, immunofluorescence imaging and flow cytometric analysis, measuring the caspase-1 activity using colorimetric assay, and quantifying the cytokines level of IL-1ß and IL-18 using ELISA, the NLRP3 inflammasome was found to be activated in a dose manner, while VX-765 and necrosulfonamide (NSA), an inhibitor of GSDMD, could inhibit PPVI-induced activation of the NLRP3 inflammasome. Furthermore, the mechanism study found that PPVI could activate the NF-κB signaling pathway via increasing reactive oxygen species (ROS) levels in A549 and H1299 cells, and N-acetyl-L-cysteine (NAC), a scavenger of ROS, remarkably inhibited the cell death, and the activation of NF-κB and the NLRP3 inflammasome in PPVI-treated A549 and H1299 cells. Taken together, these data suggested that PPVI-induced, caspase-1-mediated pyroptosis via the induction of the ROS/NF-κB/NLRP3/GSDMD signal axis in NSCLC, which further clarified the mechanism of PPVI in the inhibition of NSCLC, and thereby provided a possibility for PPVI to serve as a novel therapeutic agent for NSCLC in the future.

Novel steroidal saponin isolated from Trillium tschonoskii maxim. exhibits anti-oxidative effect via autophagy induction in cellular and Caenorhabditis elegans models.

BACKGROUND: Emerging evidences indicate the important roles of autophagy in anti-oxidative stress, which is closely associated with cancer, aging and neurodegeneration. OBJECTIVE: In the current study, we aimed to identify autophagy inducers with potent anti-oxidative effect from traditional Chinese medicines (TCMs) in PC-12 cells and C. elegans. METHODS: The autophagy inducers were extensively screened in our herbal extracts library by using the stable RFP-GFP-LC3 U87 cells. The components with autophagic induction effect in Trillium tschonoskii Maxim. (TTM) was isolated and identified by using the autophagic activity-guided column chromatography and Pre-HPLC technologies, and MS and NMR spectroscopic analysis, respectively. The anti-oxidative effect of the isolated autophagy inducers was evaluated in H2O2-induced PC-12 cells and C. elegans models by measuring the viability of PC-12 cells and C. elegans, with quantitation on the ROS level in vitro and in vivo using H2DCFDA probe. RESULTS: The total ethanol extract of TTM was found to significantly increase the formation of GFP-LC3 puncta in stable RFP-GFP-LC3 U87 cells. One novel steroidal saponin 1-O-[2,3,4-tri-O-acetyl-α-L-rhamnopyranosyl-(1→2)-4-O-acetyl-α-L-arabinopyranosyl]-21-Deoxytrillenogenin, (Deoxytrillenoside CA, DTCA) and one known steroidal saponin 1-O-[2,3,4-tri-O-acetyl-α-L-rhamnopyranosyl-(1→2)-4-O-acetyl-α-L-arabinopyranosyl]-21-O-acetyl-epitrillenogenin (Epitrillenoside CA, ETCA) were isolated, identified and found to have novel autophagic effect. Both DTCA and ETCA could activate autophagy in PC-12 cells via the AMPK/mTOR/p70S6K signaling pathway in an Atg7-dependent. In addition, DTCA and ETCA could increase the cell viability and decrease the intracellular ROS level in H2O2-treated PC-12 cells and C. elegans, and the further study demonstrated that the induced autophagy contributes to their anti-oxidative effect. CONCLUSION: Our current findings not only provide information on the discovery of novel autophagy activators from TTM, but also confirmed the anti-oxidative effect of the components from TTM both in vitro and in vivo.

Polyphyllin VI, a saponin from Trillium tschonoskii Maxim. induces apoptotic and autophagic cell death via the ROS triggered mTOR signaling pathway in non-small cell lung cancer.

Non-small cell lung cancer (NSCLC) accounts for approximately 85% of all lung cancers. Our previous studies have proven that Trillium tschonoskii Maxim. (TTM), a traditional Chinese medicine, possesses potent anti-tumor effect. However, the detailed components and molecular mechanism of TTM in anti-NSCLC are still unknown. In the present experiment, polyphyllin VI (PPVI) was successfully isolated from TTM with guidance of the anti-proliferative effect in A549 cells, and the cell death of PPVI treated A549 and H1299 cells was closely linked with the increased intracellular ROS levels. In addition, PPVI induced apoptosis by promoting the protein expression of Bax/Bcl2, caspase-3 and caspase-9, and activated autophagy by improving LC3 II conversion and GFP-LC3 puncta formation in A549 and H1299 cells. The mechanism study found that the activity of mTOR which regulates cell growth, proliferation and autophagy was significantly suppressed by PPVI. Accordingly, the PI3K/AKT and MEK/ERK pathways positively regulating mTOR were inhibited, and AMPK negatively regulating mTOR was activated. In addition, the downstream of mTOR, ULK1 at Ser 757 which downregulates autophagy was inhibited by PPVI. The apoptotic cell death induced by PPVI was confirmed, and it was significantly suppressed by the overexpression of AKT, ERK and mTOR, and the induced autophagic cell death which was depended on the Atg7 was decreased by the inhibitors, such as LY294002 (LY), Bafilomycin A1 (Baf), Compound C (CC) and SBI-0206965 (SBI). Furthermore, the mTOR signaling pathway was regulated by the increased ROS as the initial signal in A549 and H1299 cells. Finally, the anti-tumor growth activity of PPVI in vivo was validated in A549 bearing athymic nude mice. Taken together, our data have firstly demonstrated that PPVI is the main component in TTM that exerts the anti-proliferative effect by inducing apoptotic and autophagic cell death in NSCLC via the ROS-triggered mTOR signaling pathway, and PPVI may be a promising candidate for the treatment of NSCLC in future.

Virucidal activity of Garcinia parvifolia leaf extracts in animal cell culture.

BACKGROUND: Garcinia species contain bioactive compounds such as flavonoids, xanthones, triterpernoids, and benzophenones with antibacterial, antifungal, anti-inflammatory, and antioxidant activities. In addition, many of these compounds show interesting biological properties such as anti-human immunodeficiency virus activity. Garcinia parvifolia is used in traditional medicine. Currently, the antiviral activity of G. parvifolia is not known. METHODS: This study was conducted to determine the effects of ethyl acetate (45 L Ea), ethanol (45 L Et), and hexane (45 L H) leaf extracts of G. parvifolia on the infectivity of pseudorabies virus (PrV) in Vero cells. The antiviral effects of the extracts were determined by cytopathic effect (CPE), inhibition, attachment, and virucidal assays. RESULTS: The 50% cytotoxicity concentration (CC50) values obtained were 237.5, 555.0, and < 1.25 µg/mL for 45 L Ea, 45 L Et, and 45 L H, respectively. The 45 L Ea showed the greatest viral inhibition potency of 75% at 125 µg/mL. Both 45 L Ea and 45 l Et caused 100% residual viral inhibition at 250 µg/mL. The selectivity index values for 45 L Ea, 45 L Et, and 45 L H were 2.65, 1.75, and 0.10 showing that 45 L Ea had the greatest antiviral activity among the three extracts. CONCLUSION: This study showed that ethyl acetate is the best solvent to be used to obtain extract from G. parvifolia leaves with potent antiviral activities.

Polyphenols Derived from Lychee Seed Suppress Aß (1-42)-Induced Neuroinflammation.

Amyloid-ß (Aß) is commonly recognized as the most important factor that results in neuronal cell death and accelerates the progression of Alzheimer's disease (AD). Increasing evidence suggests that microglia activated by Aß release an amount of neurotoxic inflammatory cytokines that contribute to neuron death and aggravate AD pathology. In our previous studies, we found that lychee seed fraction (LSF), an active fraction derived from the lychee seed, could significantly improve the cognitive function of AD rats and inhibit Aß-induced neuroinflammation in vitro, and decrease neuronal injuries in vivo and in vitro. In the current study, we aimed to isolate and identify the specific components in LSF that were responsible for the anti-neuroinflammation effect using preparative high performance liquid chromatography (pre-HPLC), liquid chromatography-mass spectrometry (LC-MS), and nuclear magnetic resonance (NMR) methods. To this end, we confirmed two polyphenols including catechin and procyanidin A2 that could improve the morphological status of BV-2 cells and suppress the release, mRNA levels, and protein expression of pro-inflammatory cytokines such as tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and interleukin-6 (IL-6) through downregulating the nuclear factor-κB (NF-κB) signaling pathway using ELISA, RT-PCR, and Western blotting methods. Furthermore, catechin and procyanidin A2 could inhibit Aß-induced apoptosis in BV-2 cells by upregulating Bcl-2 and downregulating Bax protein expression. Therefore, the current study illustrated the active substances in lychee seed, and first reported that catechin and procyanidin A2 could suppress neuroinflammation in Aß-induced BV-2 cells, which provides detailed insights into the molecular mechanism of catechin and procyanidin A2 in the neuroprotective effect, and their further validations of anti-neuroinflammation in vivo is also essential in future research.

Antiviral activity of Embelia ribes Burm. f. against influenza virus in vitro.

Viral respiratory infections are raising serious concern globally. Asian medicinal plants could be useful in improving the current treatment strategies for influenza. The present study examines the activity of five plants from Bangladesh against influenza virus. MDCK cells infected with influenza virus A/Puerto Rico/8/34 (H1N1) were treated with increasing concentrations of ethyl acetate extracts, and their cytotoxicity (CC50), virus-inhibiting activity (IC50), and selectivity index (SI) were calculated. The ethyl acetate extract of fruits of Embelia ribes Burm. f. (Myrsinaceae) had the highest antiviral activity, with an IC50 of 0.2 µg/mL and a SI of 32. Its major constituent, embelin, was further isolated and tested against the same virus. Embelin demonstrated antiviral activity, with an IC50 of 0.3 µM and an SI of 10. Time-of-addition experiments revealed that embelin was most effective when added at early stages of the viral life cycle (0-1 h postinfection). Embelin was further evaluated against a panel of influenza viruses including influenza A and B viruses that were susceptible or resistant to rimantadine and oseltamivir. Among the viruses tested, avian influenza virus A/mallard/Pennsylvania/10218/84 (H5N2) was the most susceptible to embelin (SI = 31), while A/Aichi/2/68 (H3N2) virus was the most resistant (SI = 5). In silico molecular docking showed that the binding site for embelin is located in the receptor-binding domain of the viral hemagglutinin. The results of this study provide evidence that E. ribes can be used for development of a novel alternative anti-influenza plant-based agent.

Antibacterial effects of 18 medicinal plants used by the Khyang tribe in Bangladesh.

CONTEXT: The resistance of bacteria to antibiotics is raising serious concern globally. Asian medicinal plants could improve the current treatment strategies for bacterial infections. The antibacterial properties of medicinal plants used by the Khyang tribe in Bangladesh have not been investigated. OBJECTIVE: The present study examines the antibacterial properties of 18 medicinal plants used by the Khyang tribe in day-to-day practice against human pathogenic bacteria. MATERIALS AND METHODS: Leaves, bark, fruits, seeds, roots and rhizomes from collected plants were successively extracted with hexane, ethyl acetate and ethanol. The corresponding 54 extracts were tested against six human pathogenic bacteria by broth microdilution assay. The antibacterial mode of actions of phytoconstituents and their synergistic effect with vancomycin and cefotaxime towards MRSA was determined by time-killing assay and synergistic interaction assay, respectively. RESULTS AND DISCUSSION: Hexane extract of bark of Cinnamomum cassia (L.) J. Presl. (Lauraceae) inhibited the growth of MRSA, Enterococcus faecalis, Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae and Acinetobacter baumannii with MIC values below 100 µg/mL. From this plant, cinnamaldehyde evoked at 4 × MIC in 1 h an irreversible decrease of MRSA count Log10 (CFU/mL) from 6 to 0, and was synergistic with vancomycin for MRSA with fractional inhibitory concentration index of 0.3. CONCLUSIONS: Our study provides evidence that the medicinal plants in Bangladesh have high potential to improve the current treatment strategies for bacterial infection.

Discovery of a highly active anticancer analogue of cardamonin that acts as an inducer of caspase-dependent apoptosis and modulator of the mTOR pathway.

Cardamonin is a natural chalcone that has been shown to exhibit high anticancer activity. In an attempt to discover analogues of cardamonin with enhanced anticancer activity, 19 analogues were synthesized and tested against A549 and HK1 cell lines. Results of the MTS cell viability assay showed that several derivatives possessed cytotoxic activities that were several-fold more potent than cardamonin. SAR analysis showed the importance of the ketone and alkene groups for bioactivity, while substituting cardamonin's phenolic groups with more polar moieties resulted in activity enhancement. As part of the SAR study and further exploration of chemical space, the effect of metal coordination on cytotoxicity was also investigated, but it was only possible to successfully obtain the Cu (II) complex of cardamonin (19). Compound 19 was the most active analogue possessing IC50 values of 13.2µM and 0.7µM against A549 and HK1 cells, corresponding to a 5- and 32-fold increase in activity, respectively. It was also able to significantly inhibit the migration of A549 and HK1 cells. Further mode of action studies have shown that the most active analogue, 19, induced DNA damage resulting in G2/M-phase cell- cycle arrest in both cell lines. These events further led to the induction of apoptosis by the compound via caspase-3/7 and caspase-9 activation, PARP cleavage and downregulation of Mcl-1 expression. Moreover, 19 inhibited the expression levels of p-mTOR and p-4EBP1, which indicated that it exerted its anticancer activity, at least in part, via inhibition of the mTOR signalling pathway.

Activity of Pericampylus glaucus and periglaucine A in vitro against nasopharangeal carcinoma and anti-inflammatory activity.

ETHNOPHARMACOLOGICAL RELEVANCE: Pericampylus glaucus is a climbing plant found across Asia and used in traditional medicine to treat a number of conditions including splenomegaly, fever, cough, laryngitis, pulmonary disease, asthma, headache, hair loss, snake bite, boar bite, factures, boils, tumours, tetanus, rheumatic pain, itches and eclampsia. AIM OF THE STUDY: To test extracts of P. glaucus in a number of bioassays and determine the legitimacy of its traditional use. MATERIALS AND METHODS: The stems, leaves, roots and fruits of P. glaucus were collected and extracted sequentially with hexane, chloroform and ethanol, respectively. The anti-inflammatory activity was assessed by testing the ability of the extracts to inhibit heat induced protein denaturation, stabilise human red blood cells under hypotonic stress and by testing the inhibitory activity of the extracts against cyclooxygenases 1 and 2. Cytotoxicity was tested using the human lung epithelial cell line MRC-5 and nasopharangeal carcinoma cell line HK1 in the MTT assay. RESULTS: Many of the samples showed an ability to prevent heat induced protein denaturation, as well as prevent lysis of red blood cells. Most of the extracts demonstrated inhibitory activity towards both of the COX enzymes. The ethanol extracts tended to demonstrate greater toxicity than other extracts, with some of the other extracts significantly enhancing growth and metabolism of the cells. CONCLUSION: The benefit of P. glaucus for the treatment of diseases related to inflammation and cancer was supported by the in vitro assays adopted in this study.

Monotherapy Administration of Sorafenib in Patients With Non-Small Cell Lung Cancer (MISSION) Trial: A Phase III, Multicenter, Placebo-Controlled Trial of Sorafenib in Patients with Relapsed or Refractory Predominantly Nonsquamous Non-Small-Cell Lung Cancer after 2 or 3 Previous Treatment Regimens.

INTRODUCTION: Sorafenib monotherapy has shown benefits in phase II trials as third-/fourth-line treatment in patients with non-small-cell lung cancer (NSCLC). METHODS: The phase III, multinational, double-blind, placebo-controlled Monotherapy admInistration of Sorafenib in patientS wIth nOn-small-cell luNg cancer (MISSION) trial randomized patients with advanced relapsed/refractory NSCLC, following two or three prior treatment regimens, to sorafenib 400 mg twice a day (n = 350) or matching placebo (n = 353) plus best supportive care. The primary end point was overall survival (OS); secondary end points included progression-free survival (PFS) and time to progression. Epidermal growth factor receptor and KRAS mutation status was analyzed in archival tumor and/or circulating tumor DNA from blood samples obtained during screening. RESULTS: Median OS was similar in the sorafenib and placebo groups (8.2 versus 8.3 mo; hazard ratio [HR], 0.99; 95% confidence interval [CI], 0.84-1.17; p = 0.47). Median PFS (2.8 versus 1.4 mo; HR, 0.61; 95% CI, 0.51-0.72; p < 0.0001), and time to progression (2.9 versus 1.4 mo; HR, 0.54; 95% CI, 0.45-0.65; p < 0.0001) were significantly greater with sorafenib than with placebo. Among the 89 patients with epidermal growth factor receptor mutations, OS (13.9 versus 6.5 mo; HR, 0.48; 95% CI, 0.30-0.76; p = 0.002) and PFS (2.7 versus 1.4 mo; HR, 0.27; 95% CI, 0.16-0.46; p < 0.001) were significantly higher with sorafenib than placebo. PFS was significantly longer with sorafenib than placebo in patients with either wild-type or mutated KRAS, but OS was similar. Common drug-related adverse events were rash/desquamation, diarrhea, and fatigue, consistent with the safety profile of sorafenib. CONCLUSIONS: Third-/fourth-line sorafenib therapy did not significantly increase OS in patients with relapsed/refractory NSCLC, despite significantly increasing PFS.