Oroxin A from Oroxylum indicum improves disordered lipid metabolism by inhibiting SREBPs in oleic acid-induced HepG2 cells and high-fat diet-fed non-insulin-resistant rats.

Background: Lipid metabolism disorders have become a major global public health issue. Due to the complexity of these diseases, additional research and drugs are needed. Oroxin A, the major component of Oroxylum indicum (L.) Kurz (Bignoniaceae), can improve the lipid profiles of diabetic and insulin-resistant (IR) rats. Because insulin resistance is strongly correlated with lipid metabolism, improving insulin resistance may also constitute an effective strategy for improving lipid metabolism. Thus, additional research on the efficacy and mechanism of oroxin An under non-IR conditions is needed. Methods: In this study, we established lipid metabolism disorder model rats by high-fat diet feeding and fatty HepG2 cell lines by treatment with oleic acid and evaluated the therapeutic effect and mechanism of oroxin A in vitro and in vivo through biochemical indicator analysis, pathological staining, immunoblotting, and immunofluorescence staining. Results: Oroxin A improved disordered lipid metabolism under non-IR conditions, improved the plasma and hepatic lipid profiles, and enhanced the lipid-lowering action of atorvastatin. Additionally, oroxin A reduced the total triglyceride (TG) levels by inhibiting sterol regulatory element-binding protein 1 (SREBP1) expression and reducing the expression of acetyl coenzyme A carboxylase (ACC) and fatty acid synthase (FASN) in vivo and in vitro. Oroxin A also reduced the total cholesterol (TC) levels by inhibiting SREBP2 expression and reducing HMGCR expression in vivo and in vitro. In addition, oroxin A bound to low-density lipoprotein receptor (LDLR) and increased AMPK phosphorylation. Conclusions: Our results suggested that oroxin A may modulate the nuclear transcriptional activity of SREBPs by binding to LDLR proteins and increasing AMPK phosphorylation. Oroxin A may thus reduce lipid synthesis and could be used for the treatment and prevention of lipid metabolism disorders.

The circadian rhythm: A new target of natural products that can protect against diseases of the metabolic system, cardiovascular system, and nervous system.

BACKGROUND: The treatment of metabolic system, cardiovascular system, and nervous system diseases remains to be explored. In the internal environment of organisms, the metabolism of substances such as carbohydrates, lipids and proteins (including biohormones and enzymes) exhibit a certain circadian rhythm to maintain the energy supply and material cycle needed for the normal activities of organisms. As a key factor for the health of organisms, the circadian rhythm can be disrupted by pathological conditions, and this disruption accelerates the progression of diseases and results in a vicious cycle. The current treatments targeting the circadian rhythm for the treatment of metabolic system, cardiovascular system, and nervous system diseases have certain limitations, and the identification of safer and more effective circadian rhythm regulators is needed. AIM OF THE REVIEW: To systematically assess the possibility of using the biological clock as a natural product target for disease intervention, this work reviews a range of evidence on the potential effectiveness of natural products targeting the circadian rhythm to protect against diseases of the metabolic system, cardiovascular system, and nervous system. This manuscript focuses on how natural products restore normal function by affecting the amplitude of the expression of circadian factors, sleep/wake cycles and the structure of the gut microbiota. KEY SCIENTIFIC CONCEPTS OF THE REVIEW: This work proposes that the circadian rhythm, which is regulated by the amplitude of the expression of circadian rhythm-related factors and the sleep/wake cycle, is crucial for diseases of the metabolic system, cardiovascular system and nervous system and is a new target for slowing the progression of diseases through the use of natural products. This manuscript provides a reference for the molecular modeling of natural products that target the circadian rhythm and provides a new perspective for the time-targeted action of drugs.

High-performance heterometallic photocatalysts afforded by polyoxometalate synthons for efficient H2 production.

MoS2-based materials have emerged as photoelectric semiconductors characterized by a narrow band gap, high capacity for absorbing visible light, and reduced H2 adsorption energy comparable to Pt. These attributes render them appealing for application in photocatalytic hydrogen production. Despite these advantages, the widespread adoption of MoS2-based materials remains hindered by challenges associated with limited exposure to active sites and suboptimal catalytic hydrogen production efficiency. To address these issues, we have designed and synthesized a new class of highly dispersed bimetallic/trimetallic sulfide materials. This was achieved by developing polyoxometalate synthons containing Ni-Mo elements, which were subsequently reacted with thiourea and CdS. The resulting Ni3S2-MoS2 and Ni3S2-MoS2-CdS materials achieve photocatalytic hydrogen production rates of 2770 and 2873 µmol g-1h-1, respectively. Notably, the rate of 2873 µmol g-1h-1 for Ni3S2-MoS2-CdS surpassed triple (3.23 times) the performance of CdS and nearly sextuple (5.77 times) that of single MoS2. These materials outperformed the majority of MoS2-based photocatalysts. Overall, this study introduces a straightforward methodology for synthesizing bimetallic/trimetallic sulfides with enhanced photocatalytic H2 evolution performance. Our findings underscore the potential of transition metal sulfide semiconductors in the realm of photocatalysis and pave the way for the development of more sustainable energy production systems.

Site-selective fatty acid chain conjugation of the N-terminus of the recombinant human granulocyte colony-stimulating factor.

The clinical application of the recombinant human granulocyte colony-stimulating factor (rhG-CSF) is restricted by its short serum half-life. Herein, site-selective modification of the N-terminus of rhG-CSF with PAL-PEG3-Ph-CHO was used to develop a long-acting rhG-CSF. The optimized conditions for rhG-CSF modification with PAL-PEG3-Ph-CHO were: reaction solvent system of 3% (w/v) Tween 20 and 30 mM NaCNBH3 in acetate buffer (20 mmol/L, pH 5.0), molar ratio of PAL-PEG3-Ph-CHO to rhG-CSF of 6:1, temperature of 20°C, and reaction time of 12 h, consequently, achieving a PAL-PEG3-Ph-rhG-CSF product yield of 70.8%. The reaction mixture was purified via preparative liquid chromatography, yielding the single-modified product PAL-PEG3-Ph-rhG-CSF with a HPLC purity exceeding 95%. The molecular weight of PAL-PEG3-Ph-rhG-CSF was 19297 Da by MALDI-TOF-MS, which was consistent with the theoretical value. The circular dichroism analysis revealed no significant change in its secondary structure compared to unmodified rhG-CSF. The PAL-PEG3-Ph-rhG-CSF retained 82.0% of the in vitro biological activity of unmodified rhG-CSF. The pharmacokinetic analyses showed that the serum half-life of PAL-PEG3-Ph-rhG-CSF was 7.404 ± 0.777 h in mice, 4.08 times longer than unmodified rhG-CSF. Additionally, a single subcutaneous dose of PAL-PEG3-Ph-rhG-CSF presented comparable in vivo efficacy to multiple doses of rhG-CSF. This study demonstrated an efficacious strategy for developing long-acting rhG-CSF drug candidates.

Fibroblasts facilitate lymphatic vessel formation in transplanted heart.

Rationale: Lymphangiogenesis plays a critical role in the transplanted heart. The remodeling of lymphatics in the transplanted heart and the source of newly formed lymphatic vessels are still controversial, especially the mechanism of lymphangiogenesis remains limited. Methods: Heart transplantation was performed among BALB/c, C57BL/6J, Cag-Cre, Lyve1-CreERT2;Rosa26-tdTomato and Postn(2A-CreERT2-wpre-pA)1;Rosa26-DTA mice. scRNA-seq, Elisa assay, Western blotting, Q-PCR and immunohistochemical staining were used to identify the cells and cell-cell communications of allograft heart. Cell depletion was applied to in vivo and in vitro experiments. Whole-mount staining and three-dimensional reconstruction depicted the cell distribution within transparent transplanted heart. Results: Genetic lineage tracing mice and scRNA-seq analysis have revealed that these newly formed lymphatic vessels mainly originate from recipient LYVE1+ cells. It was found that LECs primarily interact with activated fibroblasts. Inhibition of lymphatic vessel formation using a VEGFR3 inhibitor resulted in a decreased survival time of transplanted hearts. Furthermore, when activated fibroblasts were ablated in transplanted hearts, there was a significant suppression of lymphatic vessel generation, leading to earlier graft failure. Additional investigations have shown that activated fibroblasts promote tube formation of LECs primarily through the activation of various signaling pathways, including VEGFD/VEGFR3, MDK/NCL, and SEMA3C/NRP2. Interestingly, knockdown of VEGFD and MDK in activated fibroblasts impaired cardiac lymphangiogenesis after heart transplantation. Conclusions: Our study indicates that cardiac lymphangiogenesis primarily originates from recipient cells, and activated fibroblasts play a crucial role in facilitating the generation of lymphatic vessels after heart transplantation. These findings provide valuable insights into potential therapeutic targets for enhancing graft survival.

Effects of plant natural products on metabolic-associated fatty liver disease and the underlying mechanisms: a narrative review with a focus on the modulation of the gut microbiota.

Metabolic-associated fatty liver disease (MAFLD) is a chronic liver disease characterized by the excessive accumulation of fat in hepatocytes. However, due to the complex pathogenesis of MAFLD, there are no officially approved drugs for treatment. Therefore, there is an urgent need to find safe and effective anti-MAFLD drugs. Recently, the relationship between the gut microbiota and MAFLD has been widely recognized, and treating MAFLD by regulating the gut microbiota may be a new therapeutic strategy. Natural products, especially plant natural products, have attracted much attention in the treatment of MAFLD due to their multiple targets and pathways and few side effects. Moreover, the structure and function of the gut microbiota can be influenced by exposure to plant natural products. However, the effects of plant natural products on MAFLD through targeting of the gut microbiota and the underlying mechanisms are poorly understood. Based on the above information and to address the potential therapeutic role of plant natural products in MAFLD, we systematically summarize the effects and mechanisms of action of plant natural products in the prevention and treatment of MAFLD through targeting of the gut microbiota. This narrative review provides feasible ideas for further exploration of safer and more effective natural drugs for the prevention and treatment of MAFLD.

PPARs in atherosclerosis: The spatial and temporal features from mechanism to druggable targets.

BACKGROUND: Atherosclerosis is a chronic and complex disease caused by lipid disorder, inflammation, and other factors. It is closely related to cardiovascular diseases, the chief cause of death globally. Peroxisome proliferator-activated receptors (PPARs) are valuable anti-atherosclerosis targets that showcase multiple roles at different pathological stages of atherosclerosis and for cell types at different tissue sites. AIM OF REVIEW: Considering the spatial and temporal characteristics of the pathological evolution of atherosclerosis, the roles and pharmacological and clinical studies of PPARs were summarized systematically and updated under different pathological stages and in different vascular cells of atherosclerosis. Moreover, selective PPAR modulators and PPAR-pan agonists can exert their synergistic effects meanwhile reducing the side effects, thereby providing novel insight into future drug development for precise spatial-temporal therapeutic strategy of anti-atherosclerosis targeting PPARs. KEY SCIENTIFIC: Concepts of Review: Based on the spatial and temporal characteristics of atherosclerosis, we have proposed the importance of stage- and cell type-dependent precision therapy. Initially, PPARs improve endothelial cells' dysfunction by inhibiting inflammation and oxidative stress and then regulate macrophages' lipid metabolism and polarization to improve fatty streak. Finally, PPARs reduce fibrous cap formation by suppressing the proliferation and migration of vascular smooth muscle cells (VSMCs). Therefore, research on the cell type-specific mechanisms of PPARs can provide the foundation for space-time drug treatment. Moreover, pharmacological studies have demonstrated that several drugs or compounds can exert their effects by the activation of PPARs. Selective PPAR modulators (that specifically activate gene subsets of PPARs) can exert tissue and cell-specific effects. Furthermore, the dual- or pan-PPAR agonist could perform a better role in balancing efficacy and side effects. Therefore, research on cells/tissue-specific activation of PPARs and PPAR-pan agonists can provide the basis for precision therapy and drug development of PPARs.

Achieving ultrafast and highly selective capture of radiotoxic tellurite ions on iron-based metal-organic frameworks through coordination bond-dominated conversion.

Chemically durable and effective adsorbents for radiotoxic TeOx2- (TeIV and TeVI) anions remain in great demand for contamination remediation. Herein, a low-cost iron-based metal-organic framework (MIL-101(Fe)) was used as an adsorbent to capture TeOx2- anions from contaminated solution with ultrafast kinetics and record-high adsorption capacity of 645 mg g-1 for TeO32- and 337 mg g-1 for TeO42-, outperforming previously reported adsorbents. Extended X-ray absorption fine structure (EXAFS) and density functional theory (DFT) calculations confirmed that the capture of TeOx2- by MIL-101(Fe) was mediated by the unique C-O-Te and Fe-O-Te coordination bonds at corresponding optimal adsorption sites, which enabled the selective adsorption of TeOx2- from solution and further irreversible immobilization under the geological environment. Meanwhile, MIL-101(Fe) works steadily over a wide pH range of 4-10 and at high concentrations of competing ions, and it is stable under ß-irradiation even at high dose of 200 kGy. Moreover, the MIL-101(Fe) membrane was fabricated to efficiently remove TeO32- ions from seawater for practical use, overcoming the secondary contamination and recovery problems in powder adsorption. Finally, the good sustainability of MIL-101(Fe) was evaluated from three perspectives of technology, environment, and society. Our strategy provides an alternative to traditional removal methods that should be attractive for Te contamination remediation.

One-Step Synthesis of Hollow CoS2 Spheres Derived from Polyoxometalate-Based Metal-Organic Frameworks with Peroxidase-like Activity.

In this work, hollow CoS2 particles were prepared by a one-step sulfurization strategy using polyoxometalate-based metal-organic frameworks as the precursor. The morphology and structure of CoS2 have been monitored by scanning electron microscopy, X-ray photoelectron spectroscopy, and X-ray powder diffraction. The mechanism for the formation of CoS2 is discussed. The reaction time and sulfur content are found to be important factors that affect the morphology and pure phase formation of CoS2, and a hollow semioctahedral morphology of CoS2 with open voids was obtained when the sulfur source was twice as large as the precursor and the reaction time was 24 h. The CoS2 (24 h) particles show an excellent peroxidase-like activity for the oxidation of colorless 3,3',5,5'-tetramethylbenzidine (TMB) to blue oxidized (oxTMB) by hydrogen peroxide. The polyoxometalate used as a precursor helps to stabilize oxTMB during catalytic oxidation, forming a stable curve platform for at least 8 min. Additionally, the colorimetric detection of hydroquinone is developed with a low detection limit of 0.42 µM. This research provides a new strategy to design hollow materials with high peroxidase-mimicking activity.

Attenuating effect of Polygala tenuifolia Willd. seed oil on progression of MAFLD.

Introduction: Metabolic-associated fatty liver disease (MAFLD) is a common chronic metabolic disease that seriously threatens human health. The pharmacological activity of unsaturated fatty acid-rich vegetable oil interventions in the treatment of MAFLD has been demonstrated. This study evaluated the pharmacological activity of Polygala tenuifolia Willd, which contains high levels of 2-acetyl-1,3-diacyl-sn-glycerols (sn-2-acTAGs). Methods: In this study, a mouse model was established by feeding a high-fat diet (HFD, 31% lard oil diet), and the treatment group was fed a P. tenuifolia seed oil (PWSO) treatment diet (17% lard oil and 14% PWSO diet). The pharmacological activity and mechanism of PWSO were investigated by total cho-lesterol (TC) measurement, triglyceride (TG) measurement and histopathological observation, and the sterol regulatory element-binding protein-1 (SREBP1), SREBP2 and NF-κB signaling pathways were evaluated by immunofluorescence and Western blot analyses. Results: PWSO attenuated the increases in plasma TC and TG levels. Furthermore, PWSO reduced the hepatic levels of TC and TG, ameliorating hepatic lipid accumulation. PWSO treatment effectively improves the level of hepatitic inflammation, such as reducing IL-6 levels and TNF-α level. Discussion: PWSO treatment inactivated SREBP1 and SREBP2, which are involved in lipogenesis, to attenuate hepatic lipid accumulation and mitigate the inflammatory response induced via the NF-κB signaling pathway. This study demonstrated that PWSO can be used as a relatively potent dietary supplement to inhibit the occurrence and development of MAFLD.

The combined effect of fire and nitrogen addition on biodiversity and herbaceous aboveground productivity in a coastal shrubland.

Introduction: Fire and nitrogen (N) deposition each impact biodiversity and ecosystem productivity. However, the effect of N deposition on ecosystem recovery after fire is still far from understood, especially in coastal wetlands. Methods: We selected a typical coastal shrubland to simulate three N deposition levels (0, 10, and 20 g N m-2 year-1) under two different burned conditions (unburned and burned) in the Yellow River Delta of North China. Soil properties, soil microbial biodiversity, shrub growth parameters, herbaceous biodiversity, and aboveground productivity were determined after experimental treatments for 1 year. Results: We found that fire had a stronger influence on the ecosystem than N addition. One year after the fire, shrub growth had significantly decreased, while soil pH, soil electrical conductivity, herbaceous biodiversity, soil microbial biodiversity, and herbaceous aboveground productivity significantly increased. Conversely, a single year of N addition only slightly increased herbaceous aboveground productivity. The combined effect of fire and N addition was only significant for fungus biodiversity and otherwise had minimal influence. Interestingly, we found that herbaceous aboveground productivity was positively associated with fungal community diversity under unburned conditions but not in burned shrublands. Fire showed a great impact on soil parameters and biodiversity in the coastal wetland ecosystem even after a full year of recovery. Discussion: Fire may also diminish the influence of several belowground factors on herbaceous aboveground productivity, which ultimately reduces recovery and stability. Appropriate N addition may be an effective way to improve the ecosystem productivity in a wetland dominated by shrub species.

Highly Efficient Photocatalysts: Polyoxometalate Synthons Enable Tailored CdS-MoS2 Morphologies and Enhanced H2 Evolution.

The development of photocatalysts toward highly efficient H2 evolution reactions is a feasible strategy to achieve the effective conversion of solar energy and meet the increasing demand for new energy. To this end, we prepared two different CdS-MoS2 photocatalysts with unique morphologies ranging from hexagonal prisms to tetragonal nanotubes by carefully tuning polyoxometalate synthons. These two photocatalysts, namely, CdS-MoS2-1 and CdS-MoS2-2, both exhibited remarkable photocatalytic efficiency in H2 generation, among which CdS-MoS2-2 showed superior performance. In fact, the best catalytic hydrogen desorption rate of CdS-MoS2-2 is as high as 1815.5 µmol g-1 h-1. Such performance is superior to twice that of single CdS and almost four times that of pure MoS2. This obvious enhancement can be accredited to the highly open nanotube morphology and highly dispersed heterometallic composition of CdS-MoS2-2, which represents an excellent example of the highest noble-metal-free H2 evolution photocatalysts reported so far. Taken together, these findings suggest that the development of highly dispersed heterometallic catalysts is an auspicious route to realize highly efficient conversion of solar energy and that CdS-MoS2-2 represents a major advance in this field.

The impact of microbially modified metabolites associated with obesity and bariatric surgery on antitumor immunity.

Obesity is strongly associated with the occurrence and development of many types of cancers. Patients with obesity and cancer present with features of a disordered gut microbiota and metabolism, which may inhibit the physiological immune response to tumors and possibly damage immune cells in the tumor microenvironment. In recent years, bariatric surgery has become increasingly common and is recognized as an effective strategy for long-term weight loss; furthermore, bariatric surgery can induce favorable changes in the gut microbiota. Some studies have found that microbial metabolites, such as short-chain fatty acids (SCFAs), inosine bile acids and spermidine, play an important role in anticancer immunity. In this review, we describe the changes in microbial metabolites initiated by bariatric surgery and discuss the effects of these metabolites on anticancer immunity. This review attempts to clarify the relationship between alterations in microbial metabolites due to bariatric surgery and the effectiveness of cancer treatment. Furthermore, this review seeks to provide strategies for the development of microbial metabolites mimicking the benefits of bariatric surgery with the aim of improving therapeutic outcomes in cancer patients who have not received bariatric surgery.

Oroxin B improves metabolic-associated fatty liver disease by alleviating gut microbiota dysbiosis in a high-fat diet-induced rat model.

Metabolic-associated fatty liver disease (MAFLD) has become a common chronic liver disease, but there is no FDA-approved drug for MAFLD treatment. Numerous studies have revealed that gut microbiota dysbiosis exerts a crucial effect on MAFLD progression. Oroxin B is a constituent of the traditional Chinese medicine Oroxylum indicum (L.) Kurz. (O. indicum), which has the characteristics of low oral bioavailability but high bioactivity. However, the mechanism through which oroxin B improves MAFLD by restoring the gut microbiota balance remains unclear. To this end, we assessed the anti-MAFLD effect of oroxin B in HFD-fed rats and investigated the underlying mechanism. Our results indicated that oroxin B administration reduced the lipid levels in the plasma and liver and lowered the lipopolysaccharide (LPS), interleukin 6 (IL-6), and tumor necrosis factor-α (TNF-α) levels in the plasma. Moreover, oroxin B alleviated hepatic inflammation and fibrosis. Mechanistically, oroxin B modulated the gut microbiota structure in HFD-fed rats by increasing the levels of Lactobacillus, Staphylococcus, and Eubacterium and decreasing the levels of Tomitella, Bilophila, Acetanaerobacterium, and Faecalibaculum. Furthermore, oroxin B not only suppressed Toll-like receptor 4-inhibitor kappa B-nuclear factor kappa-B-interleukin 6/tumor necrosis factor-α (TLR4-IκB-NF-κB-IL-6/TNF-α) signal transduction but also strengthened the intestinal barrier by elevating the expression of zonula occludens 1 (ZO-1) and zonula occludens 2 (ZO-2). In summary, these results demonstrate that oroxin B could alleviate hepatic inflammation and MAFLD progression by regulating the gut microbiota balance and strengthening the intestinal barrier. Hence, our study suggests that oroxin B is a promising effective compound for MAFLD treatment.

Microbially produced vitamin B12 contributes to the lipid-lowering effect of silymarin.

Silymarin has been used for improving hepatic damage and lipid disorders, but its action mechanism remains to be clarified. Here, we investigate the contributions of the gut microbiota to the improvement of liver lipid metabolism by silymarin. We find i) strong and significant microbial shifts upon silymarin but not silibinin treatment; ii) over 60% variations of liver fat are explained by silymarin-induced bacterial B12 production in male rats but not in male germ-free mice; iii) fecal microbiota transplantation confirms their protective roles against liver fat accumulation; iv) upregulation of one-carbon metabolism and fatty acid degradation pathways are observed based on the liver transcriptome analyses; and v) in humans the delta changes of serum B12 associate negatively with the fluctuations of serum triglycerides. Overall, we reveal a mechanism of action underpinning the lipid-lowering effect of silymarin via the gut microbiota and its vitamin B12 producing capabilities.

Naringenin Ameliorates Hyperuricemia by Regulating Renal Uric Acid Excretion via the PI3K/AKT Signaling Pathway and Renal Inflammation through the NF-κB Signaling Pathway.

Hyperuricemia characterized by high serum levels of uric acid (UA, >6.8 mg/dL) is regarded as a common chronic metabolic disease. When used as a food supplement, naringenin might have various pharmacological activities, including antioxidant, free-radical-scavenging, and inflammation-suppressing activities. However, the effects of naringenin on hyperuricemia and renal inflammation and the underlying mechanisms remain to be elucidated. Here, we comprehensively examined the effects of naringenin on hyperuricemia and the attenuation of renal impairment. Mice were injected with 250 mg/kg of potassium oxonate (PO) and given 5% fructose water to induce hyperuricemia. The pharmacological effects of naringenin (10 and 50 mg/kg) and benzbromarone (positive control group, 20 mg/kg) on hyperuricemic mice were evaluated in vivo. The disordered expression of urate transporters in HK-2 cells was stimulated by 8 mg/dL UA, which was used to determine the mechanisms underlying the effects of naringenin in vitro. Naringenin markedly reduced the serum UA level in a dose-dependent manner and improved renal dysfunction. Moreover, the increased elimination of UA in urine showed that the effects of naringenin were associated with the regulation of renal excretion. Further examination indicated that naringenin reduced the expression of GLUT9 by inhibiting the PI3K/AKT signaling pathway and reinforced the expression of ABCG2 by increasing the abundance of PDZK1 in vivo and in vitro. Furthermore, sirius red staining and western blotting indicated that naringenin plays a protective role in renal injury by suppressing increases in the levels of pro-inflammatory cytokines, including IL-6 and TNF-α, which contribute to the inhibition of the TLR4/NF-κB signaling pathway in vivo and in vitro. Naringenin supplementation might be a potential therapeutic strategy to ameliorate hyperuricemia by promoting UA excretion in the kidney and attenuating the inflammatory response by decreasing the release of inflammatory cytokines. This study shows that naringenin could be used as a functional food or dietary supplement for hyperuricemia prevention and treatment.

Construction of Selenium Nanoparticle-Loaded Mesoporous Silica Nanoparticles with Potential Antioxidant and Antitumor Activities as a Selenium Supplement.

Excessive reactive oxygen species (ROS) can damage cells and affect normal cell functions, which are related to various diseases. Selenium nanoparticles are a potential selenium supplement for their good biocompatibility and antioxidant activity. However, their poor stability has become an obstacle for further applications. In this study, mesoporous silica nanoparticles (MSNs) were prepared as a carrier of selenium nanoparticles. Pluronic F68 (PF68) was used for the surface modification of the compounds to prevent the leakage of the selenium nanoparticles. The prepared MSN@Se@PF68 nanoparticles were characterized by transmission electron microscopy, energy-dispersive X-ray spectroscopy, dynamic light scattering, X-ray photoelectron spectroscopy, confocal micro-Raman spectroscopy, and Fourier transform infrared spectroscopy. The MSN@Se@PF68 nanoparticles showed excellent antioxidant activity in HeLa tumor cells and zebrafish larvae. The cytotoxicity of MSN@Se@PF68 nanoparticles was concentration- and time-dependent in HeLa tumor cells. The MSN@Se@PF68 nanoparticles showed a negligible cytotoxicity of ≤2 µg/mL at 48 h. At a concentration of 50 µg/mL, the cell viability of the HeLa tumor cells decreased to about 50%. The results indicated that the MSN@Se@PF68 nanoparticles could be a potential antitumor agent. The embryonic development of zebrafish cocultured with the MSN@Se@PF68 nanoparticles showed that there was no lethal or obvious teratogenic toxicity. The results implied that the MSN@Se@PF68 nanoparticles could be a safe selenium supplement and have the potential for antioxidant and antitumor activity.

New insight into the management of renal excretion and hyperuricemia: Potential therapeutic strategies with natural bioactive compounds.

Hyperuricemia is the result of increased production and/or underexcretion of uric acid. Hyperuricemia has been epidemiologically associated with multiple comorbidities, including metabolic syndrome, gout with long-term systemic inflammation, chronic kidney disease, urolithiasis, cardiovascular disease, hypertension, rheumatoid arthritis, dyslipidemia, diabetes/insulin resistance and increased oxidative stress. Dysregulation of xanthine oxidoreductase (XOD), the enzyme that catalyzes uric acid biosynthesis primarily in the liver, and urate transporters that reabsorb urate in the renal proximal tubules (URAT1, GLUT9, OAT4 and OAT10) and secrete urate (ABCG2, OAT1, OAT3, NPT1, and NPT4) in the renal tubules and intestine, is a major cause of hyperuricemia, along with variations in the genes encoding these proteins. The first-line therapeutic drugs used to lower serum uric acid levels include XOD inhibitors that limit uric acid biosynthesis and uricosurics that decrease urate reabsorption in the renal proximal tubules and increase urate excretion into the urine and intestine via urate transporters. However, long-term use of high doses of these drugs induces acute kidney disease, chronic kidney disease and liver toxicity. Therefore, there is an urgent need for new nephroprotective drugs with improved safety profiles and tolerance. The current systematic review summarizes the characteristics of major urate transporters, the mechanisms underlying the pathogenesis of hyperuricemia, and the regulation of uric acid biosynthesis and transport. Most importantly, this review highlights the potential mechanisms of action of some naturally occurring bioactive compounds with antihyperuricemic and nephroprotective potential isolated from various medicinal plants.

Network pharmacology analysis to explore mechanism of Three Flower Tea against nonalcoholic fatty liver disease with experimental support using high-fat diet-induced rats.

Objective: Nonalcoholic fatty liver disease (NAFLD) has become a common chronic liver disease that is harmful to human health. Moreover, there is currently no FDA-approved first-line drug for the treatment of nonalcoholic steatohepatitis (NASH) or NAFLD. Traditional Chinese medicine (TCM) is widely used to ameliorate liver diseases, such as the traditional ancient recipe called Three Flower Tea (TFT), which consists of double rose (Rosa rugosa), white chrysanthemum (Chrysanthemum morifolium), and Daidaihua (Citrus aurantium). However, the mechanisms of the action of TFT are not clear. Therefore, this study aimed to elucidate the mechanisms of TFT against NAFLD in high-fat diet (HFD)-induced rats. Methods: This study utilized bioinformatics and network pharmacology to establish the active and potential ingredient-target networks of TFT. Furthermore, a protein-protein interaction (PPI) network was constructed, and enrichment analysis was performed to determine the key targets of TFT against NAFLD. Furthermore, an animal experiment was conducted to evaluate the therapeutic effect and confirm the key targets of TFT against NAFLD. Results: A total of 576 NAFLD-related genes were searched in GeneCards, and under the screening criteria of oral bioavailability (OB) ≥30% and drug-likeness (DL) ≥0.18, a total of 19 active ingredients and 210 targets were identified in TFT. Network pharmacology analysis suggested that 55 matching targets in PPIs were closely associated with roles for NAFLD treatment. Through the evaluation of network topology parameters, four key central genes, PPARγ, SREBP, AKT, and RELA, were identified. Furthermore, animal experiments indicated that TFT could reduce plasma lipid profiles, hepatic lipid profiles and hepatic fat accumulation, improve liver function, suppress inflammatory factors, and reduce oxidative stress. Through immunoblotting and immunofluorescence analysis, PPARγ, SREBP, AKT, and RELA were confirmed as targets of TFT in HFD-induced rats. Conclusion: In summary, our results indicate that TFT can prevent and treat NAFLD via multiple targets, including lipid accumulation, antioxidation, insulin sensitivity, and inflammation.

Genetic characterization of a novel HIV­1 CRF01_AE/ CRF07_BC recombinant form found among men who have sex with men in Baoding City, Hebei Province, China.

Large numbers of unique recombinant forms (URF) of human immunodeficiency virus (HIV-1) have been found among sexual transmission populations in China. Here, we report a novel second-generation URF of HIV-1 named BD201AQ that was isolated from an HIV-1-positive man who was infected through homosexual transmission in Baoding City, Hebei Province, China. Phylogenetic analysis based on the near-full-length genome (NFLG) sequence indicated that BD201AQ formed a monophyletic branch that did not cluster with other HIV-1 subtypes. Recombination analysis showed that the NFLG of BD201AQ had 12 segments, six CRF07_BC and six CRF01_AE segments, with CRF07_BC as the main framework. These findings indicate that the constant emergence of novel recombinant forms should receive more attention and that more measures should be taken to monitor the molecular epidemiological characteristics of HIV-1 and to prevent the spread of HIV-1 infections.