Ochratoxin A detoxification potentials of basil, chan, and chia seeds.

The most toxic of the ochratoxins is ochratoxin A (OTA), which is primarily produced by species of Aspergillus and Penicillium that can be found in maize, wheat, coffee, red wine, and various grains. OTA induces immunotoxicity, nephrotoxicity, hepatotoxicity, teratogenicity, and carcinogenicity in both animals and humans. Thus, there is a need to identify mycotoxin detoxification agents that can effectively decontaminate OTA. Seeds of basil (Ocimum basilicum L.), chan (Hyptis suaveolens L.), and chia (Salvia hispanica L.) are functional foods capable of eliminating harmful substances. Despite this potential, the impact of these seeds on OTA detoxification remains unclear. This study reveals that milled basil, chan, and chia seeds adsorb significant levels of OTA, with chia demonstrating the highest adsorption capacity, followed by chan and basil seeds showing the least efficiency. Furthermore, milled basil, chan, and chia seeds effectively reduced OTA residues in artificial gastric and intestinal fluids, where they achieved up to 93% OTA adsorption in the former. In addition, these milled seeds were able to remove OTAs from canned, drip, and instant coffee. This study is the first to report the OTA elimination potential of basil, chan, and chia seeds.

Long-term efficacy of hydrotherapy on balance function in patients with Parkinson's disease: a systematic review and meta-analysis.

Background: Hydrotherapy can improve the motor and non-motor symptoms of Parkinson's disease (PD), but the long-term effects of hydrotherapy on PD are still unclear. Objective: The purpose of this systematic evaluation and meta-analysis was to explore the long-term effects of hydrotherapy on balance function in PD patients. Methods: A systematic search of five databases was conducted to identify appropriate randomized controlled trials (RCTs) according to the established inclusion and exclusion criteria. The general characteristics and outcome data (balance, exercise, mobility, quality of life, etc.) of the included studies were extracted, and the quality of the included studies was evaluated using the Cochrane risk of bias assessment tool. Finally, the outcome data were integrated for meta-analysis. Results: A total of 149 articles were screened, and 5 high-quality RCTs involving 135 PD patients were included. The results of the meta-analysis showed positive long-term effects of hydrotherapy on balance function compared to the control group (SMD = 0.69; 95% CI = 0.21, 1.17; p = 0.005; I2 = 44%), However, there were no significant long-term effects of hydrotherapy on motor function (SMD = 0.06; 95% CI = -0.33, 0.44; p = 0.77; I2 = 0%), mobility and quality of life (SMD = -0.21; 95% CI = -0.98, 0.57; p = 0.6; I2 = 71%). Interestingly, the results of the sensitivity analysis performed on mobility showed a clear continuation effect of hydrotherapy on mobility compared to the control group (SMD = -0.80; 95% CI = -1.23, -0.37; p < 0.001; I2 = 0%). Conclusion: The long-term effects of hydrotherapy on PD patients mainly focus on balance function, and the continuous effects on motor function, mobility, and quality of life are not obvious.

Functional Axis of PDE5/cGMP Mediates Timosaponin-AIII-Elicited Growth Suppression of Glioblastoma U87MG Cells.

Glioblastoma (GBM) is the most aggressive brain tumor, with high mortality. Timosaponin AIII (TIA), a steroidal saponin isolated from the medicinal plant Anemarrhena asphodeloides Bge., has been shown to possess anticancer properties in various cancer types. However, the effect of TIA on GBM is unknown. In this study, we reveal that TIA not only inhibited U87MG in vitro cell growth but also in vivo tumor development. Moreover, we found that the cause of TIA-induced cell growth suppression was apoptosis. When seeking to uncover antitumor mechanisms of TIA, we found that TIA diminished the expression of cGMP-specific phosphodiesterase 5(PDE5) while elevating the levels of guanylate cyclases (sGCß), cellular cGMP, and phosphorylation of VASPser239. Following the knockdown of PDE5, PDE5 inhibitor tadalafil and cGMP analog 8-Bro-cGMP both inhibited cell growth and inactivated ß-catenin; we reason that TIA elicited an antitumor effect by suppressing PDE5, leading to the activation of the cGMP signaling pathway, which, in turn, impeded ß-catenin expression. As ß-catenin is key for cell growth and survival in GBM, this study suggests that TIA elicits its anti-tumorigenic effect by interfering with ß-catenin function through the activation of a PDE5/cGMP functional axis.

Efficacy of Repeated Low-Level Red-Light Therapy for Slowing the Progression of Childhood Myopia: A Systematic Review and Meta-analysis.

PURPOSE: To evaluate the long-term efficacy and safety of repeated low-intensity red light (RLRL) treatment for childhood myopia. DESIGN: Systematic review and meta-analysis METHODS: We searched PubMed, Web of Science, CNKI, and Wanfang from inception to February 8, 2023. We used the RoB 2.0 and ROBINS-I tools to assess the risk of bias and then used a random-effect model to calculate the weighted mean difference (WMD) and 95% CIs. The primary outcomes were WMD in spherical equivalent refractive error (SER), WMD in axial length (AL), and WMD in subfoveal choroid thickness (SFChT). Subgroup analyses were performed to investigate the sources of heterogeneity based on variation in follow-up and study design. The Egger and Begg tests were used to assess publication bias. Sensitivity analysis was used to verify the stability. RESULTS: This analysis included 13 studies (8 randomized controlled trials, 3 non-randomized controlled trials, and 2 cohort studies) involving 1857 children and adolescents. Eight studies met the meta-analysis criteria, and the WMD for myopia progression between RLRL and the control group was 0.68 diopters (D) per 6 months (95% CI = 0.38 to 0.97 D; I2 = 97.7%; P < .001) for SER change; -0.35 mm per 6 months (95% CI = -0.51 to -0.19 mm; I2 = 98.0%; P < .001) for AL elongation; and 36.04 µm per 6 months (95% CI = 19.61 to 52.48 µm; I2 = 89.6%; P < .001) for SFChT change. CONCLUSIONS: Our meta-analysis shows that RLRL therapy may be effective for delaying the progression of myopia. The evidence is low certainty, and larger and better randomized clinical trials with 2-year follow-ups are needed to improve the existing state of knowledge to inform medical guidelines more comprehensively.

Effect of hot water extracts of Arthrospira maxima (spirulina) against respiratory syncytial virus.

BACKGROUND: Spirulina (Arthrospira maxima) hot water extracts such as calcium spirulan (Ca-SP) have demonstrated antiviral effects against herpes simplex virus (HSV), human immunodeficiency virus-1 (HIV-1), and influenza virus infections. There is no prior evidence suggesting the anti-viral activity of the spirulina hot water extract against respiratory syncytial virus (RSV). PURPOSE: There are currently no effective antivirals available to treat RSV infection. Therefore, the development of safe and novel anti-RSV drugs is urgent and necessary. The aim of this work was to demonstrate the anti-RSV activity of spirulina hot water extracts and determine the potential mechanism of action. METHODS: Cytotoxicity and anti-RSV activity of spirulina hot water extracts were measured using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and neutralization assays, respectively. Potential mechanisms and components were assessed using time of addition, attachment, internalization, pull-down assays, and composition analysis. RESULTS: The polysaccharide-enriched high-molecular weight fraction (>100 kDa, SHD1) had a high total sugar content, with rhamnose accounting for approximately 60 mol% of total monosaccharides. The main glycosyl linkages included 3-, 4-, and 2,3-rhamnopyranosyl linkages. All spirulina hot water extracts showed no toxicity toward human epithelial type 2 (HEp-2) cells but demonstrated anti-RSV activity. The SHD1 had a half maximal effective concentration (EC50) of 0.0915 mg/ml and a selective index (SI) of >261.5 against RSV. SHD1 significantly reduced viral yield in a dose-dependent manner during the RSV attachment stage. SHD1 disrupted RSV internalization and inhibited RSV attachment (G) protein binding to heparan sulfate receptors on the host cell surface, thus preventing RSV attachment and entry. CONCLUSION: SHD1 serves as an effective candidate for novel drug development against RSV infection.

Low-intensity red-light therapy in slowing myopic progression and the rebound effect after its cessation in Chinese children: a randomized controlled trial.

PURPOSE: To investigate the effect of low-intensity red-light (LRL) therapy on myopic control and the response after its cessation. METHODS: A prospective clinical trial. One hundred two children aged 6 to 13 with myopia were included in the LRL group (n = 51) and the single-focus spectacles (SFS) group (n = 51). In LRL group, subjects wore SFS and received LRL therapy provided by a laser device that emitted red-light of 635 nm and power of 0.35 ± 0.02 mW. One year after the control trial, LRL therapy was stopped for 3 months. The outcomes mainly included axial length (AL), spherical equivalent refraction (SER), subfoveal choroidal thickness (SFCT), and accommodative function. RESULTS: After 12 months of therapy, 46 children in the LRL group and 40 children in the SFS group completed the trial. AL elongation and myopic progression were 0.01 mm (95%CI: - 0.05 to 0.07 mm) and 0.05 D (95%CI: - 0 .08 to 0.19 D) in the LRL group, which were less than 0.39 mm (95%CI: 0.33 to 0.45 mm) and - 0.64 D (95%CI: - 0.78 to - 0.51 D) in the SFS group (p < 0.05). The change of SFCT in the LRL group was greater than that in the SFS group (p < 0.05). Accommodative response and positive relative accommodation in the LRL group were more negative than those in the SFS group (p < 0.05). Forty-two subjects completed the observation of LRL cessation, AL and SER increased by 0.16 mm (95%CI: 0.11 to 0.22 mm) and - 0.20 D (95%CI: - 0.26 to - 0.14 D) during the cessation (p < 0.05), and SFCT returned to baseline (p > 0.05). CONCLUSIONS: LRL is an effective measure for preventing and controlling myopia, and it may also have the ability to improve the accommodative function. There may be a slight myopic rebound after its cessation. The effect of long-term LRL therapy needs to be further explored. TRIAL REGISTRATION: Chinese Clinical Trial Registry: Chinese Clinical Trails registry: ChiCTR2100045250. Registered 9 April 2021; retrospectively registered. http://www.chictr.org.cn/showproj.aspx?proj=124250.

Antiliver Fibrosis Formula of Fuzheng Huayu Alleviates Inflammatory Response.

Fuzheng Huayu's (FZHY) formula ameliorated liver fibrosis in clinical and experimental practice. Based on the close link between fibrosis and inflammation, its anti-inflammatory effect and related mechanisms were explored in this present study. With the aid of the inflammatory macrophage model, FZHY significantly blocked nitrite accumulation without observable cytotoxicity due to its suppression of inducible nitric oxide synthase (iNOS) gene and protein expressions in a concentration-depended manner. Proinflammatory mediators including IL-6, CD86, and CD40 were also restrained by FZHY. Interestingly, FZHY induced anti-inflammatory mediators heme oxygenase 1 (HO-1) and peroxisome proliferator-activated receptor γ (PPAR-γ) expressions simultaneously. Downregulation of iNOS and miR-155 and upregulation of PPAR-γ were also observed in CCl4-induced liver fibrosis mice upon FZHY administration. Mechanically, FZHY strikingly eliminated the phosphorylation of STAT1 and MAPK. Taken together, FZYH regulated the balance of proinflammatory and anti-inflammatory mediators partially via modulating STAT1/MAPK pathways and the miR-155/PPAR-γ axis.

[Mechanism of timosaponin Aâ ¢ in regulation of metabolism against glioblastoma growth].

Non-targeted metabonomics was used to investigate the metabolite changes in the glioblastoma orthotopic tumor-bearing mice after timosaponin AⅢ(TIA) intervention to explore the metabolic relevant mechanism of glioblastoma and TIA intervention. The mice were randomly divided into a blank group, a model group, and a TIA group. HPLC-LTQ-Orbitrap Elite liquid chromatography-mass spectrometry was used to detect the metabolite changes in the serum of rats in the three groups after treatment for 4 weeks. Principal component analysis(PCA) and orthogonal partial least squares discriminant analysis(OPLS-DA) were performed on the metabolites, and the differential metabolites were selected based on VIP values and P values(P<0.05). The results showed that TIA significantly inhibited the in vivo glioblastoma growth, but it had limited influence on body weight. Serum samples were clearly distinguishable among groups. As compared with the blank group, six metabolites including ceramide, succinic acid, α-ketoglutarate acid(αKG), citric acid, indophenol sulfate, and 3 a, 6 b, 7 b-trihydroxy-5 b-cholic acid in the model group significantly decreased. As compared with the model group, five metabolites except phenol sulfate, PC[20:4(5Z,7E,11Z,14Z)-OH(9)/diMe(9,3)], o-palmitoyl carnitine, α-ketoglutarate acid, and citric acid in the TIA group significantly increased. According to the MetaboAnalyst enrichment analysis, the metabolic pathways were enriched in the tricarboxylic acid cycle, and alanine, aspartic acid, and glutamate metabolism. These results show that during the glioblastoma growth process, the metabolites including αKG and citric acid are down-regulated, and TIA exerts the anti-glioblastoma growth effect through the regulation of tricarboxylic acid cycle, and alanine, aspartic acid, and glutamate metabolism to elevate the levels of αKG, citric acid, and other metabolites.

1,2,4-Trimethoxybenzene selectively inhibits NLRP3 inflammasome activation and attenuates experimental autoimmune encephalomyelitis.

NOD-like receptor (NLR) family pyrin domain-containing-3 (NLRP3) inflammasome is implicated in inflammation-associated diseases such as multiple sclerosis, Parkinson's disease, and stroke. Targeting the NLRP3 inflammasome is beneficial to these diseases, but few NLRP3 inflammasome-selective inhibitors are identified to date. Essential oils (EOs) are liquid mixtures of volatile and low molecular-weight organic compounds extracted from aromatic plants, which show various pharmacological activities, including antibacterial, antifungal, antiviral, antioxidant, and anti-inflammatory properties. In this study we screened active ingredients from essential oils, and identified 1,2,4-trimethoxybenzene (1,2,4-TTB) as a selective NLRP3 inflammasome inhibitor. We showed that 1,2,4-TTB (1 mM) markedly suppressed nigericin- or ATP-induced NLRP3 inflammasome activation, thus decreased caspase-1 activation and IL-1ß secretion in immortalized murine bone marrow-derived macrophages (iBMDMs) and in primary mouse microglia. Moreover, 1,2,4-TTB specifically inhibited the activation of NLRP3 inflammasome without affecting absent in melanoma 2 (AIM2) inflammasome activation. We further demonstrated that 1,2,4-TTB inhibited oligomerization of the apoptosis-associated speck-like protein containing a CARD (ASC) and protein-protein interaction between NLRP3 and ASC, thus blocking NLRP3 inflammasome assembly in iBMDMs and in primary mouse macrophages. In mice with experimental autoimmune encephalomyelitis (EAE), administration of 1,2,4-TTB (200 mg · kg-1 · d-1, i.g. for 17 days) significantly ameliorated EAE progression and demyelination. In conclusion, our results demonstrate that 1,2,4-TTB is an NLRP3 inflammasome inhibitor and attenuates the clinical symptom and inflammation of EAE, suggesting that 1,2,4-TTB is a potential candidate compound for treating NLRP3 inflammasome-driven diseases, such as multiple sclerosis.

The Impact of Phosphorus on Plant Immunity.

Phosphorus (P) is the second most essential macronutrient in terms of limiting plant growth. The genes involved in P acquisition, transport, storage, utilization and respective regulation have been extensively studied. In addition, significant attention has been given to the crosstalk between P and other environmental stresses. In this review, we summarize recent discoveries pertaining to the emerging function of P in plant immunity. The roles of external soil P availability, internal cellular P in plants, P starvation signaling machinery and phosphate transporters in biotic interactions are discussed. We also highlight the impact of several phytohormones on the signaling convergence between cellular P and immune responses. This information may serve as a foundation for dissecting the molecular interaction between nutrient responses and plant immunity.

Excess incidence and risk factors for recurrent pneumonia in bipolar disorder.

AIM: Patients with bipolar disorder (BD) tend to have poorer outcomes after pneumonia and could have a higher risk for recurrence of pneumonia. We aimed to investigate the incidence and risk factors of recurrent pneumonia in patients with BD. METHODS: In a nationwide cohort of BD patients (derived from the National Health Insurance Research Database in Taiwan) who were hospitalized for pneumonia between 1996 and 2012, we identified 188 patients who developed recurrent pneumonia after a baseline pneumonia episode. Applying risk-set sampling at a 1:2 ratio, 353 matched controls were selected from the study cohort. We used multivariate conditional logistic regression analysis to explore the association between recurrent pneumonia and physical illness, concomitant medications, and psychotropic drugs. RESULTS: The findings showed that the incidence of recurrent pneumonia in BD was 6.60 cases per 100 person-years, which was higher than that in the general population. About 10% (9.24%) of cases with recurrent pneumonia died within 30 days of hospitalization. Patients had increased risk of recurrent pneumonia if they had hypertension, diabetes mellitus, cancer, or asthma. Conversely, psychotropic drugs, both first- and second-generation antipsychotics, which are known to increase susceptibility to baseline pneumonia, were not associated with risk of pneumonia recurrence. CONCLUSION: We found an excess incidence of recurring pneumonia in patients with BD, and this risk was associated with pre-existing medical conditions but not psychotropic agents. Physicians should carefully consider the comorbid medical conditions of patients with BD that could lead to recurrent pneumonia.

Aloe-Emodin Enhances Tamoxifen Cytotoxicity by Suppressing Ras/ERK and PI3K/mTOR in Breast Cancer Cells.

Aloe-emodin (AE) is derived from Aloe vera and rhubarb (Rheum palmatum) and exhibits anticancer activities via multiple regulatory mechanisms in various cancers. AE can also enhance the anticancer efficacy of cisplatin, doxorubicin, docetaxel, and 5-fluorouracil; however, its effects remain poorly characterized. MCF-7, MDA-MB-231, MDA-MB-468, BT-474, and HCC-1954 breast cancer cell lines were treated with the indicated conditions of AE, and cell viability assays were performed. The expression levels of signaling proteins were determined by western blot analysis, intracellular reactive oxygen species (ROS), cell cycle distributions, and rates of apoptosis as estimated by flow cytometry. In comparison with other cells, MCF-7 cells were more sensitive to AE treatment; AE enhanced the cytotoxicity of 9[Formula: see text][Formula: see text]g/ml tamoxifen by reducing EGFR, ER[Formula: see text], Ras, ERK, c-Myc, and mTOR protein expression and blocking PI3K and mTOR activation. Finally, although co-treatment of AE with tamoxifen increased intracellular ROS, there were no effects on cell cycle progression. Besides facilitating tamoxifen-induced cell death, AE also enhanced the antiproliferative activity of tamoxifen by blocking Ras/ERK and PI3K/mTOR pathways in breast cancer cells, thus demonstrating the chemosensitizing potential of AE.

Aqueous extract of Anisomeles indica and its purified compound exerts anti-metastatic activity through inhibition of NF-κB/AP-1-dependent MMP-9 activation in human breast cancer MCF-7 cells.

Anisomeles indica popularly known in Taiwan as 'yu-chen-tsao' has been traditionally used as an anticancer and anti-inflammatory agent; however, little is known about its anti-metastatic potential. Therefore, we attempted in this study to examine the anti-metastatic potential of A. indica aqueous extract (AI), its isolated compounds apigenin, ovatodiolide, ß-sitosterol and acteoside in 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced human breast adenocarcinoma MCF-7 cells. Among the test agents, crude extract AI and pure compound apigenin potently suppressed the TPA-induced MCF-7 cells migration and invasion. In addition, AI and apigenin time- and dose-dependently down regulated the matrix metalloproteinase (MMP)-9 enzymatic activities and its mRNA expression. Furthermore, AI and apigenin also down regulated the nuclear factor (NF)-κB subunit p65, and activator protein (AP)-1 subunit c-Fos proteins expression in nucleus and, transcriptional activity of NF-κB and AP-1. This is the first report on the anti-metastatic potential of A. indica that suppressed the cancer cell invasion through the inhibition of MMP-9 enzyme via NF-κB/AP-1 signaling. Taken together, our data indicate that A. indica can be considered as a source of new anti-metastatic agent for food and pharmaceutical industries.

Ornithine decarboxylase prevents dibenzoylmethane-induced apoptosis through repressing reactive oxygen species generation.

Dibenzoylmethane (DBM) belongs to the flavonoid family and is a minor constituent of the root extract of licorice and the ß-diketone analogue of curcumin. It exhibits antimutagenic, anticancer, and chemopreventive effects. Ornithine decarboxylase (ODC), the rate-limiting enzyme of the polyamine biosynthetic pathway, plays an important role in growth, proliferation, and transformation. Our previous studies showed ODC overexpression prevented etoposide-, paclitaxel-, and cisplatin-induced apoptosis. Here, we investigated one mechanism of DBM-induced apoptosis and the antiapoptotic effects of ODC during DBM treatment. We found that DBM induced apoptosis, promoted reactive oxygen species (ROS) generation, and disrupted the mitochondrial membrane potential (Δψ(m). N-acetylcysteine, a ROS scavenger, reduced DBM-induced apoptosis, which led to the loss of Δψ(m) due to reduced ROS. Overexpression of ODC in parental cells had the same effects as the ROS scavenger. The results demonstrated that DBM-induced apoptosis was a ROS-dependent pathway and ODC overexpression blocked DBM-induced apoptosis by inhibiting intracellular ROS production.