Nighttime administration of antihypertensive medication: a review of chronotherapy in hypertension.

Hypertension remains a global health concern because of suboptimal blood pressure control despite advancements in antihypertensive treatments. Chronotherapy, defined as evening or bedtime administration of medication based on biological rhythms, is emerging as a potential strategy to improve blood pressure control and treatment outcomes. Clinical trials have investigated the potential effects of nighttime administration of antihypertensive medication in the improvement of 24 hours blood pressure control and reduction of cardiovascular risk. Implementing chronotherapy in clinical practice could have significant implications in enhancing blood pressure control and improving clinical outcomes in patients with hypertension, particularly those with resistant hypertension. However, recent trials have reported contradictory results, causing confusion in real-world practice. Herein we review, analyze, and critique the current evidence and propose suggestions regarding the clinical application and future directions of chronotherapy.

Hydrogel design to overcome thermal resistance and ROS detoxification in photothermal and photodynamic therapy of cancer.

Responsive heat resistance (by heat shock protein upregulation) and spontaneous reactive oxygen species (ROS) detoxification have been regarded as the major obstacles for photothermal/photodynamic therapy of cancer. To overcome the thermal resistance and improve ROS susceptibility in breast cancer therapy, Au ion-crosslinked hydrogels including indocyanine green (ICG) and polyphenol are devised. Au ion has been introduced for gel crosslinking (by catechol-Au3+ coordination), cellular glutathione depletion, and O2 production from cellular H2O2. ICG can generate singlet oxygen from O2 (for photodynamic therapy) and induce hyperthermia (for photothermal therapy) under the near-infrared laser exposure. (-)-Epigallocatechin gallate downregulates heat shock protein to overcome heat resistance during hyperthermia and exerts multiple anticancer functions in spite of its ironical antioxidant features. Those molecules are concinnously engaged in the hydrogel structure to offer fast gel transformation, syringe injection, self-restoration, and rheological tuning for augmented photo/chemotherapy of cancer. Intratumoral injection of multifunctional hydrogel efficiently suppressed the growth of primary breast cancer and completely eliminated the residual tumor mass. Proposed hydrogel system can be applied to tumor size reduction prior to surgery of breast cancer and the complete remission after its surgery.

Supplementation with a high-glucose drink stimulates anti-tumor immune responses to glioblastoma via gut microbiota modulation.

A high-sugar diet induces lifestyle-associated metabolic diseases, such as obesity and diabetes, which may underlie the pro-tumor effects of a high-sugar diet. We supply GL261 syngeneic glioblastoma (GBM) mice with a short-term high-glucose drink (HGD) and find an increased survival rate with no evidence of metabolic disease. Modulation of the gut microbiota through HGD supplementation is critical for enhancing the anti-tumor immune response. Single-cell RNA sequencing shows that gut microbiota modulation by HGD supplementation increases the T cell-mediated anti-tumor immune response in GBM mice. We find that the cytotoxic CD4+ T cell population in GBM is increased due to synergy with anti-programmed cell death protein 1 (anti-PD-1) immune checkpoint inhibitors, but this effect depends upon HGD supplementation. Thus, we determine that HGD supplementation enhances anti-tumor immune responses in GBM mice through gut microbiota modulation and suggest that the role of HGD supplementation in GBM should be re-examined.

Alum-tuned hyaluronic acid-based hydrogel with immune checkpoint inhibition for immunophoto therapy of cancer.

Alum-crosslinked hyaluronic acid-dopamine (HD) hydrogel containing indocyanine green (ICG) with anti-programmed cell death-1 (PD-1) antibody (Ab) administration was developed for immunophoto therapy of cancer. Alum modulates the rheological characteristics of hydrogel for enabling syringe injection, shear-thinning feature, and slower biodegradation. In addition, alum in HD-based hydrogel provided CD8+ T cell-mediated immune responses for cancer therapy. ICG in the hydrogel under near-infrared (NIR) light exposure may induce hyperthermia and generate singlet oxygen for selective cancer cell killing. HD/alum/ICG hydrogel injection with NIR laser irradiation elevated PD-1 level in CD8+ T cells. Administration of PD-1 Ab aiming at highly expressed PD-1 in T cells may amplify the anticancer efficacies of HD/alum/ICG hydrogel along with NIR laser. HD/alum/ICG hydrogel with NIR light may have both CD8+ T cell-linked immune responses and ICG-related photodynamic/photothermal effects. Additional injection of immune checkpoint inhibitor can ultimately suppress primary and distant tumor growth by combination with those therapeutic actions.

Aloe-derived nanovesicles attenuate inflammation and enhance tight junction proteins for acute colitis treatment.

Inflammatory bowel disease (IBD) is a chronic recurrent inflammatory disease of the digestive tract that causes pain and weight loss and also increases the risk of colon cancer. Inspired by the benefits of plant-derived nanovesicles and aloe, we herein report aloe-derived nanovesicles, including aloe vera-derived nanovesicles (VNVs), aloe arborescens-derived nanovesicles (ANVs), and aloe saponaria-derived nanovesicles (SNVs) and evaluate their therapeutic potential and molecular mechanisms in a dextran sulfate sodium (DSS)-induced acute experimental colitis mouse model. Aloe-derived nanovesicles not only facilitate markedly reduced DSS-induced acute colonic inflammation, but also enable the restoration of tight junction (TJ) and adherent junction (AJ) proteins to prevent gut permeability in DSS-induced acute colonic injury. These therapeutic effects are ascribed to the anti-inflammatory and anti-oxidant effects of aloe-derived nanovesicles. Therefore, aloe-derived nanovesicles are a safe treatment option for IBD.

Terbium-Rose Bengal Coordination Nanocrystals-Induced ROS Production under Low-Dose X-rays in Cultured Cancer Cells for Photodynamic Therapy.

X-ray-triggered scintillators (Sc) and photosensitizers (Ps) have been developed for X-ray-induced photodynamic therapy (X-PDT) to selectively destruct deep tissue tumors with a low X-ray dose. This study designed terbium (Tb)-rose bengal (RB) coordination nanocrystals (T-RBNs) by a solvothermal treatment, aiming to reduce photon energy dissipation between Tb3+ and RB and thus increase the reactive oxygen species (ROS) production efficiency. T-RBNs synthesized at a molar ratio of [RB]/[Tb] = 3 exhibited a size of 6.8 ± 1.2 nm with a crystalline property. Fourier transform infrared analyses of T-RBNs indicated successful coordination between RB and Tb3+. T-RBNs generated singlet oxygen (1O2) and hydroxyl radicals (•OH) under low-dose X-ray irradiation (0.5 Gy) via scintillating and radiosensitizing pathways. T-RBNs produced ∼8-fold higher ROS amounts than bare RB and ∼3.6-fold higher ROS amounts than inorganic nanoparticle-based controls. T-RBNs did not exhibit severe cytotoxicity up to 2 mg/mL concentration in cultured luciferase-expressing murine epithelial breast cancer (4T1-luc) cells. Furthermore, T-RBNs were efficiently internalized into cultured 4T1-luc cells and induced DNA double strand damage, as evidenced by an immunofluorescence staining assay with phosphorylated γ-H2AX. Ultimately, under 0.5 Gy X-ray irradiation, T-RBNs induced >70% 4T1-luc cell death via simultaneous apoptosis/necrosis pathways. Overall, T-RBNs provided a promising Sc/Ps platform under low-dose X-PDT for advanced cancer therapy.

Direct Monitoring of Membrane Fatty Acid Changes and Effects on the Isoleucine/Valine Pathways in an ndgR Deletion Mutant of Streptomyces coelicolor.

NdgR, a global regulator in soil-dwelling and antibiotic-producing Streptomyces, is known to regulate branched-chain amino acid metabolism by binding to the upstream region of synthetic genes. However, its numerous and complex roles are not yet fully understood. To more fully reveal the function of NdgR, phospholipid fatty acid (PLFA) analysis with gas chromatography-mass spectrometry (GC-MS) was used to assess the effects of an ndgR deletion mutant of Streptomyces coelicolor. The deletion of ndgR was found to decrease the levels of isoleucine- and leucine-related fatty acids but increase those of valine-related fatty acids. Furthermore, the defects in leucine and isoleucine metabolism caused by the deletion impaired the growth of Streptomyces at low temperatures. Supplementation of leucine and isoleucine, however, could complement this defect under cold shock condition. NdgR was thus shown to be involved in the control of branched-chain amino acids and consequently affected the membrane fatty acid composition in Streptomyces. While isoleucine and valine could be synthesized by the same enzymes (IlvB/N, IlvC, IlvD, and IlvE), ndgR deletion did not affect them in the same way. This suggests that NdgR is involved in the upper isoleucine and valine pathways, or that its control over them differs in some respect.

Effects of dietary glycerol supplementation on meat quality, palatability, and lipid metabolism gene expression in the longissimus thoracis of Hanwoo steers.

This study tested the hypothesis that dietary glycerol supplementation (GS) would affect growth of Hanwoo steers, beef marbling and palatability, and gene expression for lipid uptake and transport and lipogenesis in the longissimus thoracis (LT). Diets with or without 45.2 g daily glycerol supplementation/kg dry matter concentrate were tested in fourteen Hanwoo steers during a 16-week feeding trial. GS did not affect (P ≥ 0.40) the average daily gain or the gain-to-feed ratio. GS increased the LT marbling score (P = 0.01). GS enhanced (P ≤ 0.01) the sensory traits, including the flavor and overall acceptance of the LT. GS tended (0.05 < P ≤ 0.10) to upregulate mRNA levels of fatty acid translocase, lipoprotein lipase, and fatty acid binding protein 4 genes in the LT. These tendencies of upregulated expression of fatty acid uptake and cytosolic transport genes may, in part, contribute to the increased marbling by GS. The increased marbling degree caused by GS may improve palatability including the flavor and overall acceptance of the LT.

Lucidumol A, Purified Directly from Ganoderma lucidum, Exhibits Anticancer Effect and Cellular Inflammatory Response in Colorectal Cancer.

Colorectal cancer (CRC) is a deadly disease regardless of sex, and a few therapeutic approaches have been fully developed at advanced stages, even if some strategies have durable clinical benefits, such as immunotherapy and chemotherapy. Ganoderma lucidum has been recognized as an organism that suppresses tumors and inflammation; however, the molecular mechanisms induced by a triterpenoid in Ganoderma lucidum, Lucidumol A, have not yet been fully explored in CRC and inflammatory responses. To this end, we extracted Lucidumol A from Ganoderma lucidum and analyzed its anticancer effect and anti-inflammatory potential in CRC cell lines and RAW264.7 macrophage-derived cell lines, respectively. A series of in vitro experiments including cell survival, wound healing, and migration assays were performed to determine the role of Lucidumol A in the CRC cell line. We also analyzed inflammatory responses using qRT-PCR, Western Blot, and ELISA in RAW 264.7 macrophaged-derived cell lines exposed to various concentrations of Lucidumol A. Lucidumol A efficiently suppressed the metastatic potential of CRC at very low concentrations. Furthermore, significant anti-inflammatory activities were observed in Lucidumol A-treated RAW264.7 cells through modulation of inflammation-associated marker genes and cytokines. In conclusion, Lucidumol A plays an important role in Ganoderma lucidum-dependent tumor suppression and anti-inflammation, suggesting different strategies to treat CRC patients, and other diseases evoked by proinflammatory cytokines, despite the need to explore further its mechanism of action.

Rose Bengal Decorated NaYF4:Tb Nanoparticles for Low Dose X-ray-Induced Photodynamic Therapy in Cancer Cells.

The use of scintillating nanoparticles (ScNPs) in X-ray-induced photodynamic therapy (X-PDT) is a technique for deep tissue-localized tumor therapy with few side effects. ScNPs transfer X-ray-induced energy to photosensitizers, which generate massive amounts of reactive oxygen species (ROS) and kill cancer cells. Here we fabricated rose bengal (RB)-installed, Tb3+-rich NaYF4 nanocrystals (NaYF4:Tb@RB), in which optically inert Y3+ enables highly efficient energy transfer via high amounts of Tb3+ doping. NaYF4:Tb was prepared via solvothermal synthesis to have an average size of 7.6 nm, followed by coating with poly(maleic anhydride-alt-1-octedecene)-poly(ethylene glycol) with a molecular weight of 2000 (C18PMH-PEG2k). Further, RB was covalently conjugated to carboxyl groups generated from PMH on NaYF4:Tb using an ethylenediamine linker. NaYF4:Tb@RB exhibited a hydrodynamic diameter of ∼75 nm with a ζ-potential of -12 mV. NaYF4:Tb@RB efficiently generated ROS in cultured luciferase-expressing murine epithelial breast cancer (4T1-luc) cells under low dose X-ray irradiation (0.5 Gy). The ROS generation amounts of NaYF4:Tb@RB were 1.5-2-fold higher than those of NaGdF4:Tb@RB, in which host nanocrystals were prepared with optically active Gd3+. Flow cytometric and confocal microscopic analyses showed higher intracellular ROS production of NaYF4:Tb@RB, compared to NaYF4:Tb and RB, resulting in higher X-ray-induced DNA damage in cultured 4T1-luc cells. Ultimately, NaYF4:Tb@RB elicited significant cytotoxicity after X-ray irradiation (0.5 Gy), while inducing marginal cytotoxicity without X-ray irradiation. Altogether, this research proposes a promising ScNP design for efficient X-PDT agents that make the better use of incident X-ray energy while causing the fewest side effects.

Inhibitory Effects of Acetyloctadecadienediynoic Acid Isolated from Leaves of Dendropanax morbiferus on Viability and Self-Renewal Activity of Glioma Stem-Like Cells.

Glioblastoma (GBM) is one of the most dangerous brain tumors in humans. The median survival of patients with GBM is <18 months. Glioma stem-like cells (GSCs), a small subpopulation of cells with stem cell-like characteristics found within GBM, are regarded as the main cause of GBM malignancy. Therefore, targeting GSCs presents an important therapeutic strategy for reducing the aggressiveness of tumors. In this study, we examined effects of (9Z,16S)-16-O-acetyl-9,17-octadecadiene-12,14-diynoic acid (AODA), a diacetylenic carboxylic acid isolated from leaves of Dendropanax morbiferus, on viability and self-renewal activity of GSCs. AODA substantially decreased GSC growth, causing apoptotic cell death as assessed by Annexin V/PI staining and morphological alterations by optical diffraction tomography. Interestingly, treatment with AODA suppressed ''stem-like features'' in vitro by limiting dilution assays and real-time polymerase chain reaction analysis. In addition, Western blotting revealed that AODA treatment decreased expression levels of phosphorylated AKT and phosphorylated ERK in GSC11 cells. Taken together, our results indicate that AODA could be considered a new therapeutic candidate to target GSCs.

Walnut Prevents Cognitive Impairment by Regulating the Synaptic and Mitochondrial Dysfunction via JNK Signaling and Apoptosis Pathway in High-Fat Diet-Induced C57BL/6 Mice.

This study was conducted to evaluate the protective effect of Juglans regia (walnut, Gimcheon 1ho cultivar, GC) on high-fat diet (HFD)-induced cognitive dysfunction in C57BL/6 mice. The main physiological compounds of GC were identified as pedunculagin/casuariin isomer, strictinin, tellimagrandin I, ellagic acid-O-pentoside, and ellagic acid were identified using UPLC Q-TOF/MS analysis. To evaluate the neuro-protective effect of GC, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), 2',7'-dichlorodihydrofluorecein diacetate (DCF-DA) analysis were conducted in H2O2 and high glucose-induced neuronal PC12 cells and hippocampal HT22 cells. GC presented significant cell viability and inhibition of reactive oxygen species (ROS) production. GC ameliorated behavioral and memory dysfunction through Y-maze, passive avoidance, and Morris water maze tests. In addition, GC reduced white adipose tissue (WAT), liver fat mass, and serum dyslipidemia. To assess the inhibitory effect of antioxidant system deficit, lipid peroxidation, ferric reducing antioxidant power (FRAP), and advanced glycation end products (AGEs) were conducted. Administration of GC protected the antioxidant damage against HFD-induced diabetic oxidative stress. To estimate the ameliorating effect of GC, acetylcholine (ACh) level, acetylcholinesterase (AChE) activity, and expression of AChE and choline acetyltransferase (ChAT) were conducted, and the supplements of GC suppressed the cholinergic system impairment. Furthermore, GC restored mitochondrial dysfunction by regulating the mitochondrial ROS production and mitochondrial membrane potential (MMP) levels in cerebral tissues. Finally, GC ameliorated cerebral damage by synergically regulating the protein expression of the JNK signaling and apoptosis pathway. These findings suggest that GC could provide a potential functional food source to improve diabetic cognitive deficits and neuronal impairments.

Plum Prevents Intestinal and Hepatic Inflammation in the Acute and Chronic Models of Dextran Sulfate Sodium-Induced Mouse Colitis.

SCOPE: Inflammatory bowel disease (IBD), including ulcerative colitis (UC), is a chronic recurrent inflammatory disease of the digestive tract and increases the risk of colon cancer. METHOD AND RESULTS: This study evaluates the effects of dietary intervention with freeze-dried plum (FDP), a natural antioxidant and anti-inflammatory fruit with no toxicity on dextran sulfate sodium (DSS)-induced acute and chronic experimental colitis in a mouse model and studies the molecular mechanisms of protection through the gut-liver axis. The results show that FDP decreases the levels of inflammatory mediators, which is a nitrative stress biomarker in both acute and chronic models. FDP markedly reduces DSS-induced injury to the colonic epithelium in both acute and chronic models. In addition, FDP significantly decreases the levels of pro-oxidant markers such as CYP2E1, iNOS, and nitrated proteins (detected by anti-3-NT antibody) in DSS-induced acute and chronic colonic injury models. Furthermore, FDP markedly reduces markers of liver injury such as serum ALT/AST, antioxidant markers, and inflammatory mediators in DSS-induced acute and chronic colonic injury. CONCLUSION: These results demonstrate that the FDP exhibits a protective effect on DSS-induced acute and chronic colonic and liver injury through the gut-liver axis via antioxidant and anti-inflammatory properties.

Oral Microbiome Using Colocasia antiquorum var. esculenta Extract Varnish in a Mouse Model with Oral Gavage of P. gingivalis ATCC 53978.

Background and Objective: There is increasing interest in preventing periodontitis using natural products. The purpose of this study was to investigate the effect of Colocasia antiquorum var. esculenta (CA) varnish on the oral microbiome and alveolar bone loss in a mouse periodontitis model. Materials and Methods: Antibacterial activity against Porphyromonas gingivalis (P. gingivalis) ATCC 53978 and cell cytotoxicity using CCK-8 on L929 cells were measured. Balb/c mice were assigned into five groups (negative control, positive control, CA in drinking water, varnish, and CA varnish). P. gingivalis was administered to the mice by oral gavage three times. After sacrifice, the oral microbiome and the levels of the inflammatory cytokine IL-1ß and matrix metalloproteinase-9 were analyzed. Alveolar bone loss was measured using micro-computed tomography. Results: CA extract showed an antibacterial effect against P. gingivalis (p < 0.05) and showed no cytotoxicity at that concentration (p > 0.05). Although alpha diversity of the oral microbiome did not statistically differ between the groups (p > 0.05), the relative abundance of dominant bacteria tended to be different between the groups. The inflammatory cytokine IL-1ß was reduced in the CA varnish group (p < 0.05), and no difference was observed in MMP-9 expression and alveolar bone loss (p > 0.05). Conclusions: CA varnish did not affect the overall microflora and exhibited an anti-inflammatory effect, suggesting that it is possibility a suitable candidate for improving periodontitis.

Anticancer Activity of 2-O-caffeoyl Alphitolic Acid Extracted from the Lichen, Usnea barbata 2017-KL-10.

Colorectal cancer is one of the life-threatening ailments causing high mortality and morbidity worldwide. Despite the innovation in medical genetics, the prognosis for metastatic colorectal cancer in patients remains unsatisfactory. Recently, lichens have attracted the attention of researchers in the search for targets to fight against cancer. Lichens are considered mines of thousands of metabolites. Researchers have reported that lichen-derived metabolites demonstrated biological effects, such as anticancer, antiviral, anti-inflammatory, antibacterial, analgesic, antipyretic, antiproliferative, and cytotoxic, on various cell lines. However, the exploration of the biological activities of lichens' metabolites is limited. Thus, the main objective of our study was to evaluate the anticancer effect of secondary metabolites isolated from lichen (Usnea barbata 2017-KL-10) on the human colorectal cancer cell line HCT116. In this study, 2OCAA exhibited concentration-dependent anticancer activities by suppressing antiapoptotic genes, such as MCL-1, and inducing apoptotic genes, such as BAX, TP53, and CDKN1A(p21). Moreover, 2OCAA inhibited the migration and invasion of colorectal cancer cells in a concentration-dependent manner. Taken together, these data suggest that 2OCAA is a better therapeutic candidate for colorectal cancer.

Immature Persimmon Suppresses Amyloid Beta (Aß) Mediated Cognitive Dysfunction via Tau Pathology in ICR Mice.

This study confirmed the ameliorating effect of immature persimmon (Diospyros kaki) ethanolic extract (IPEE) on neuronal cytotoxicity in amyloid beta (Aß)1-42-induced ICR mice. The administration of IPEE ameliorated the cognitive dysfunction in Aß1-42-induced mice by improving the spatial working memory, the short-term and long-term memory functions. IPEE protected the cerebral cholinergic system, such as the acetylcholine (ACh) level and acetylcholinesterase (AChE) activity, and antioxidant system, such as the superoxide dismutase (SOD), reduced glutathione (GSH) and malondialdehyde (MDA) contents. In addition, mitochondrial dysfunction against Aß1-42-induced toxicity was reduced by regulating the reactive oxygen species (ROS), mitochondrial membrane potential and ATP contents. In addition, IPEE regulated the expression levels of tau signaling, such as TNF-α, p-JNK, p-Akt, p-GSK3ß, p-tau, p-NF-κB, BAX and caspase 3. Finally, gallic acid, ellagic acid and quercetin 3-O-(6″-acetyl-glucoside) were identified as the physiological compounds of IPEE using ultra-performance liquid chromatography ion mobility separation quadrupole time-of-flight/tandem mass spectrometry (UPLC IMS Q-TOF/MS2).

Chondroprotective effect of Alpinia oxyphylla extract in experimentally induced cartilage degradation in rabbit articular cartilage explants.

Alpinia oxyphylla is a widely used medicinal herb for diarrhea, gastralgia, tumors, hypertention, and cerebrovascular disorders. Here, we evaluated the chondroprotective effect of A. oxyphylla dried fruit ethanol extract (AOE) against cartilage degradation in rabbit articular cartilage explants. Treatment of interleukin-1α (IL-1α) and plasminogen increased degraded collagen release in culture supernatants, but pretreatment of AOE (50, 100, 200 µg/ml) inhibited the collagen release in dose-dependent manner. To examine the mechanism of action of AOE on chondroprotection, the level of matrix metalloproteinases-3 (MMP-3), matrix metalloproteinases-13 (MMP-13), tissue inhibitor of metalloprotease-1 (TIMP-1), and inflammatory mediators like prostaglandin E2 (PGE2 ) and nitric oxide (NO) was evaluated. AOE inhibited upregulation of MMP-3 and MMP-13 and downregulation of TIMP-1 and also reduced increase of PGE2 and NO level induced by exposure of IL-1α and plasminogen. These results indicate that AOE show chondroprotective effect through inhibiting collagen degradation via regulating MMPs, TIMP-1, and inflammatory mediators. PRACTICAL APPLICATIONS: Osteoarthritis (OA) is a one of the most common chronic disorders in elderly persons. Because the regenerative power of joint articular cartilage is very low, treatment of OA is difficult to expect complete recovery. Therefore, there is a need to develop a therapeutic agent that can safely and effectively inhibit the cartilage destruction. For the first time, we exhibited the inhibitory effect of AOE on collagen degradation through regulating MMPs and TIMP-1 in articular cartilage explants. These findings support AOE could be used as herbal therapeutic application for protecting articular cartilage to prevent OA.

Protection of palmitic acid treatment in RAW264.7 cells and BALB/c mice during Brucella abortus 544 infection.

BACKGROUND: We previously elucidated the protective mechanism of Korean red ginseng oil (RGO) against Brucella abortus infection, and our phytochemical analysis revealed that palmitic acid (PA) was an abundant component of RGO. Consequently, we investigated the contribution of PA against B. abortus. OBJECTIVES: We aimed to investigate the efficacy of PA against B. abortus infection using a murine cell line and a murine model. METHODS: Cell viability, bactericidal, internalization, and intracellular replication, western blot, nitric oxide (NO), and superoxide (O2⁻) analyses and flow cytometry were performed to determine the effects of PA on the progression of B. abortus infection in macrophages. Flow cytometry for cytokine analysis of serum samples and bacterial counts from the spleens were performed to determine the effect of PA in a mouse model. RESULTS: PA did not affect the growth of B. abortus. PA treatment in macrophages did not change B. abortus uptake but it did attenuate the intracellular survivability of B. abortus. Incubation of cells with PA resulted in a modest increase in sirtuin 1 (SIRT1) expression. Compared to control cells, reduced nitrite accumulation, augmented O2⁻, and enhanced pro-inflammatory cytokine production were observed in PA-treated B. abortus-infected cells. Mice orally treated with PA displayed a decreased serum interleukin-10 level and enhanced bacterial resistance. CONCLUSIONS: Our results suggest that PA participates in the control of B. abortus within murine macrophages, and the in vivo study results confirm its efficacy against the infection. However, further investigations are encouraged to completely characterize the mechanisms involved in the inhibition of B. abortus infection by fatty acids.

Effects of germination and roasting on physicochemical and sensory characteristics of brown rice for tea infusion.

Germinated brown rice was roasted for the preparation of tea. The germination induced substantial increases in reducing sugars (from 3224.06 to 5028.80 mg/100 g), free amino acids (from 62.51 to 165.07 mg/100 g), volatile compounds, and phenolics (10.06 to 14.27 mg GAE/100 g). Roasting decreased the residual contents of free amino acids and reducing sugars, but produced the volatiles and phenolics. Browning index was slightly decreased by the germination (from 22.69 to 20.13), but significantly increased by the subsequent roasting. The germinated BR (GBR) was more susceptible to roasting than native BR. Acrylamide content in the roasted GBR was significantly lower than that in the roasted BR, because of the lower asparagine content in GBR. Sensory evaluation revealed that a mild roasting for 5 min at 230 °C after germination for 2 days was appropriate to produce a brown rice tea.

Efficacy and safety of thermal ablation for autonomously functioning thyroid nodules: a systematic review and meta-analysis.

BACKGROUND: Although thermal ablation has been regarded as an alternative treatment option for autonomously functioning thyroid nodules (AFTNs), the efficacy of this treatment in patients with AFTNs has not yet been systematically evaluated. In this systematic review and meta-analysis, we aimed to evaluate the efficacy and safety of thermal ablation in the treatment of AFTN, and identify the factors affecting the effectiveness of the treatment. METHODS: Ovid-MEDLINE and Embase databases were searched for studies reporting the efficacy and safety of thermal ablation for patients with AFTN published up until January 6, 2020. Data extraction and quality assessment were performed by two radiologists according to PRISMA guidelines. The primary and secondary outcomes were to yield the pooled proportions of thyroid-stimulating hormone (TSH) normalization and pooled estimates of volume reduction rate (VRR), respectively. Subgroup analyses were performed to identify factors affecting the treatment efficacy. RESULTS: This systematic review identified 411 AFTNs treated by thermal ablation in 391 patients in 14 studies. TSH normalization was achieved in 71.2% of patients and the volume reduction rate was 69.4% at a mean follow-up period of 12.8 months. No patients experienced hypothyroidism or a life-threatening complication during follow-up. Subgroup analyses according to nodule volume did not find a significant difference in TSH normalization (p = 0.54) or VRR (p = 0.94). CONCLUSIONS: Thermal ablation is an effective and safe treatment method for patients with AFTNs. The nodule volume did not affect the efficacy of thermal ablation, and this result should be considered in future thermal ablation guidelines. KEY POINTS: • Thermal ablation has good efficacy and safety in the treatment of autonomously functioning thyroid nodule. • The efficacy of thermal ablation was not affected by nodule volume.