CHEMICO-BIOLOGICAL INTERACTIONS
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2024
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IF 4.7
Aijie Zhang,Shiqi Dong,Fanlong Yang,Yufeng Zhang,Yunhua Teng,Weisheng Tang,Jianfeng Liu,Huirong Fan,Ying Peng,Jiang Zheng
ABSTRACT Pharmacokinetic changes induced by radiation following radiotherapy (“RT-PK” phenomenon) are of great significance to the effectiveness and safety of chemotherapeutic agents in clinical settings. The aims of this study were to clarify the organic anion transporters (Oats) involved in the “RT-PK” phenomenon of bestatin in rats following X-ray irradiation and to elucidate its potential mechanism via vitamin D signalling. Pharmacokinetic studies, uptake assays using rat kidney slices and primary proximal tubule cells, and molecular biological studies were performed. Significantly increased plasma concentrations and systemic exposure to bestatin were observed at 24 and 48 h following abdominal X-ray irradiation, regardless of oral or intravenous administration of the drugs in rats. Reduced renal clearance and cumulative urinary excretion of bestatin were observed at 24 and 48 h post-irradiation in rats following intravenous administration. The uptake of the probe substrates p -aminohippuric acid and oestrone 3-sulphate sodium in vitro and the expression of Oat1 and Oat3 in vivo were reduced in the corresponding models following irradiation. Moreover, the upregulation of the vitamin D receptor (Vdr) in mRNA and protein levels negatively correlated with the expressions and functions of Oat1 and Oat3 following irradiation. Additionally, elevated plasma urea nitrogen levels and histopathological changes were observed in rats after exposure to irradiation. The “RT-PK” phenomenon of bestatin occurs in rats after exposure to irradiation, possibly resulting in the regulation of the expressions and activities of renal Oats via activation of the Vdr signalling pathway.
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Molecular Medicine Reports
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2025
·Vol. 31
·期 3
·1-12
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IF 3.5
Xiangli Yan,Siqi Quan,Roujia Guo,Zibo Li,Ming Bai,Baoying Wang,Pan Su,Erping Xu,Yucheng Li
Calycosin‑7‑O‑β‑D‑glucoside (CG), a major active ingredient of Astragali Radix, exerts neuroprotective effects against cerebral ischemia; however, whether the effects of CG are associated with mitochondrial protection remains unclear. The present study explored the role of CG in improving mitochondrial function in a HT22 cell model of oxygen‑glucose deprivation/reperfusion (OGD/R). The Cell Counting Kit‑8 assay, flow cytometry, immunofluorescence and western blotting were performed to investigate the effects of CG on mitochondrial function. The results demonstrated that mitochondrial function was restored after treatment with CG, as indicated by reduced mitochondrial reactive oxygen species levels, increased mitochondrial membrane potential and improved mitochondrial morphology. Overactivated mitophagy was revealed to be inhibited by the regulation of proteins involved in fission [phosphorylated‑dynamin‑related protein 1 (Drp1) and Drp1] and mitophagy (LC3, p62 and translocase of outer mitochondrial membrane 20), and mitochondrial biogenesis was demonstrated to be enhanced by increased levels of sirtuin 1 (SIRT1) and peroxisome proliferator‑activated receptor γ coactivator‑1α (PGC‑1α). In addition, neuronal apoptosis was ameliorated by CG, as determined by a decreased rate of apoptosis, and levels of caspase‑3 and Bcl‑2/Bax. In conclusion, the present study demonstrated that CG may alleviate OGD/R‑induced injury by upregulating SIRT1 and PGC‑1α protein expression, and reducing excessive mitochondrial fission and overactivation of mitophagy.
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BIOORGANIC CHEMISTRY
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2024
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IF 4.5
Muhammad Waheed Iqbal,Xinrui Tang,Tahreem Riaz,Shahid Mahmood,Yufei Zhang,Mei Zhao,Junhua Yun,Jia Li,Xianghui Qi
6-Deoxy- l -sorbose (6-DLS) is an imperative rare sugar employed in food, agriculture, pharmaceutical and cosmetic industeries. However, it is a synthetic and very expensive rare sugars, previously synthesized by chemo-enzymatic methods through a long chain of chemical processes. Recently, enzymatic synthesis of rare sugars has attracted a lot of attention due to its advantages over synthetic methods. In this work, a promising approach for the synthesis of 6-DLS from an inexpensive sugar l -fucose was identified. The genes for l -fucose isomerase from Paenibacillus rhizosphaerae (Pr-LFI) and genes for d -tagatose-3-epimerase from Caballeronia fortuita (Cf-DTE) have been used for cloning and co-expression in Escherichia coli , developed a recombinant plasmid harboring pANY1-Pr-LFI/Cf-DTE vector. The recombinant co-expression system exhibited an optimum activity at 50 °C of temperature and pH 6.5 in the presence of Co 2+ metal ion which inflated the catalytic activity by 6.8 folds as compared to control group with no metal ions. The recombinant co-expressed system was stable up to more than 50 % relative activity after 12 h and revealed a melting temperature (T m ) of 63.38 °C exhibiting half-life of 13.17 h at 50 °C. The co-expression system exhibited, 4.93, 11.41 and 16.21 g/L of 6-DLS production from initial l -fucose concentration of 30, 70 and 100 g/L, which equates to conversion yield of 16.44 %, 16.30 % and 16.21 % respectively. Generally, this study offers a promising strategy for the biological production of 6-DLS from an inexpensive substrate l -fucose in slightly acidic conditions with the aid of co-expression system harboring Pr-LFI and CF-DTE genes.
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Food Bioscience
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2024
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IF 4.8
Linhui Feng,Heping Cui,Khizar Hayat,Xiaoming Zhang,Chi-Tang Ho
The Amadori rearrangement product (GR-ARP) derived from glutathione/ribose mixture (GSH/Rib) was prepared through spray drying characterized by short-term high temperature dehydration. The water activity of spray-dried samples containing GR-ARP decreased continuously with an intensified degree of dehydration. Lower water activity (from 0.23 to 0.13) and higher GR-ARP yield (from 46.56% to 64.02%) in the spray-dried products were found with the increase of inlet temperature, the slowdown of feed speed, and the alkalization of stock solution. Moreover, during the spray drying and formation of powders, the intensified dissipation of bound water to free water promoted intermolecular condensation that compensated bound water, favoring the directed conversion of GSH/Rib into GR-ARP. Compared to rotary evaporation at 80 °C, spray drying enabled a stronger restraint of amide cleavage and sulfhydryl oxidation in GSH, which reduced the yield of GSH-derived byproducts by 16.39%. Thus, GR-ARP was achieved a peak yield of 64.02% at an initial pH of 7.00 based on more efficient intermolecular condensation and controlled side reactions of GSH when the inlet temperature was set at 170 °C. The spray-dried sample containing richer GR-ARP and other flavor precursors showed a more similar flavor profile to the heated GSH/Rib mixture (complete Maillard reaction products) than other GR-ARP-related thermal processing samples, such as vacuum-dehydrated, GR-ARP, GR-ARP + GSH, and GR-ARP + Rib samples, revealing a great potential of the ARP mixture prepared by spray drying for flavor enhancement.
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JOURNAL OF ETHNOPHARMACOLOGY
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2024
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IF 4.8
Yun-Lu Xu,Xue-Jian Li,Wei Cai,Wen-Ying Yu,Jing Chen,Qin Lee,Yong-Jun Choi,Fang Wu,Ying-Jun Lou,Hua-Zhong Ying,Chen-Huan Yu,Qiao-Feng Wu
Ethnopharmacological relevance Viral pneumonia is the leading cause of death after SARS-CoV-2 infection. Despite effective at early stage, long-term treatment with glucocorticoids can lead to a variety of adverse effects and limited benefits. The Chinese traditional herb Pogostemonis Herba is the aerial part of Pogostemon Cablin (Blanco) Benth., which has potent antiviral, antibacterial, anti-inflammatory, and anticancer effects. It was used widely for treating various throat and respiratory diseases, including COVID-19, viral infection, cough, allergic asthma, acute lung injury and lung cancer. Aim of the study To investigate the antiviral and anti-inflammatory effects of chemical compounds from Pogostemonis Herba in SARS-CoV-2-infected hACE2-overexpressing mouse macrophage RAW264.7 cells and hACE2 transgenic mice. Materials and methods The hACE2-overexpressing RAW264.7 cells were exposed with SARS-CoV-2. The cell viability was detected by CCK8 assay and cell apoptotic rate was by flow cytometric assay. The expressions of macrophage M1 phenotype markers (TNF-α and IL-6) and M2 markers (IL-10 and Arg-1) as well as the viral loads were detected by qPCR. The mice were inoculated intranasally with SARS-CoV-2 omicron variant to induce viral pneumonia. The levels of macrophages, neutrophils, and T cells in the lung tissues of infected mice were analyzed by full spectrum flow cytometry. The expressions of key proteins were detected by western blot assay. Results Diosmetin-7-O-β-D-glucopyranoside (DG) presented the strongest anti-SARS-CoV-2 activity. Intervention with DG at the concentrations of 1.25-50 μM not only reduced the viral replication, cell apoptosis, and the productions of inflammatory cytokines (IL-6 and TNF-α) in SARS-CoV-2-infected RAW264.7 cells, but also reversed macrophage polarity from M1 to M2 phenotype. Furthermore, treatment with DG (25-100 mg/kg) alleviated acute lung injury, and reduced macrophage infiltration in SARS-COV-2-infected mice. Mechanistically, DG inhibited SARS-COV-2 gene expression and HK3 translation via targeting YTHDF1, resulting in the inactivation of glycolysis-mediated NF-κB pathway. Conclusions DG exerted the potent antiviral and anti-inflammatory activities. It reduced pneumonia in SARS-COV-2-infected mice via inhibiting the viral replication and accelerating M2 macrophage polarization via targeting YTHDF1, indicating its potential for COVID-19 treatment.
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Advanced Healthcare Materials
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2024
·
IF 10
Yixuan Xu,Huiping Dang,Changchang Teng,Dalong Yin,Lifeng Yan
Rapid propagation of tumor cells requires plenty of energy, which is adenosine triphosphate (ATP) dependent. ATP inhibition in tumors not only results in the starvation of tumor cells but also down-regulation of the level of heat shock proteins (HSPs), which usually increase during traditional photothermal therapy (PTT), especially when the temperature is up 50 °C. 2-deoxy-D-glucose (2DG) is an anti-glycolytic reagent and can be used as an efficient agent for ATP inhibition in tumors. Compared with typical PTT, low-temperature mild photothermal therapy (MPTT) is receiving more and more attention because it avoids the high temperatures causing damage to the normal tissue, and the increase of HSPs which decrease PTT. Here, multifunctional polypeptide nanoparticles pDG@Ahx conjugating both a NIR probe Ahx-BDP and 2DG into the side chain of the amphiphilic polypeptide have been prepared. In vitro and in vivo studies reveal that the as-prepared nanoparticles achieve a synergistic effect of starvation/MPTT/PDT (photodynamic therapy), and it provides a new strategy to NIR-I/II fluorescence imaging-guided starvation/MPTT/PDT synergy therapy for tumors.
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SPECTROCHIMICA ACTA PART A-MOLECULAR AND BIOMOLECULAR SPECTROSCOPY
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2024
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IF 4.3
Mingyi Guan,Hui Li,Man Tu,Chenchen Fu,Xiyu Yang,Feng Wang
Trivalent chromium (Cr 3+ ) causes serious environmental pollution, degradation of the quality of edible agricultural products and human diseases. A novel phenanthro[9,10-d]imidazole-derived conjugated polymers (PIPF) was obtained from 4-(5,10-dibromo-1H-phenanthro[9,10-d]imidazol-2-yl)phenol and diethyl 4,4′-(2,7-bis(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-9H-fluorene-9,9-diyl)dibutyrate by Suzuki polymerization reaction, which was reasonably demonstrated by 1 H NMR spectroscopy, infrared spectroscopy and quantum chemical calculations. The PIPF exhibits a “turn-on” fluorescence response to Cr 3+ in DMSO/H 2 O (98:2, v/v) with naked-eye detection. The limit of detection for Cr 3+ was calculated to be 0.073 μM with a linear range of 3–9 μM. The possible mechanism of the PIPF-based Cr 3+ fluorescence “turn-on” sensor is due to the inhibition of the PET process by the coordination of Cr 3+ to the hexaalkyl ester carbon chain of PIPF (RCOO-). The high sensitivity, good selectivity, and utility of this sensor indicated that PIPF-based “turn-on” fluorescence sensor is a potential fluorescence application for measuring Cr 3+ in environmental samples.
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JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
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2025
·
IF 6.2
Yuvaraj Ravikumar,Abdullah Arsalan,Xinrui Tang,Guoyan Zhang,Xianghui Qi
l-Arabinose isomerase (l-AI) catalyzes d-galactose to produce the rare, industrially important sugar d-tagatose. Enzyme stability is vital for its application in industrial processes, and rational design-based protein engineering methods have been employed to improve its stability. This study employed molecular dynamics simulations (MDS)-guided rational redesign of flexible regions to improve the thermostability of mesophilic Bifidobacterium adolescentis l-AI (Ba-l-AI). Comparative MDS (200 ns, 340–360 K) of thermophilic l-AIs (Geobacillus kaustophilus Gk-l-AI and Thermotoga maritima Tm-l-AI) and mesophilic Ba-l-AI identified flexible regions in Ba-l-AI via RMSF and ionic interaction. Five stabilizing mutations (G78C, K46R, N187R, K112R, and N190R) were introduced to provide rigidness. MDS of the mutant revealed reduced RMSF/RMSD, improved compactness, and enhanced conformational stability across temperatures, supported by free-energy landscape analysis resembling thermophilic profiles. Experimentally, the mutant exhibited superior thermal stability (72 °C), broader pH/temperature tolerance, and efficient d-tagatose production. The redesigned Ba-l-AI’s rigid backbone and stability highlight its potential for industrial d-tagatose biosynthesis.
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ADVANCED FUNCTIONAL MATERIALS
·
2025
·
IF 19
Fan Li,Shang Sun,Lina Ma,Wenjing Zhang,Min Zhou,Yu Fu,Hengrui Guo,Xueying Su,Jinliang Shi,Hao Luo,Yang Yang
The intrinsically low electrical conductivity of elemental iodine and its slow redox kinetics represent two significant obstacles that hinder the commercialization of aqueous zinc-iodine batteries. These challenges can be addressed by modulating the adsorption-desorption equilibrium of iodide ions in the active material. This study presented a synergistic strategy of “Electronic Modulation” and “Phase Transition Engineering” to optimize the catalytic adsorption-desorption dynamics. A dual-designed Fe ions doped VO 2- x heterostructure anchored on reduced graphene oxide (Fe-VO 2- x /rGO) is demonstrated to synchronously adjust iodine adsorption and boost redox kinetics. The Fe-induced electronic structure modulation elevated the d-band center of vanadium, creating catalytic sites to promote the desorption of iodide ions and facilitate their diffusion. Concurrently, the phase transition from VO 2- x to V 2 O 5- n within the heterostructure establishes a 3D conductive network, synergizing with rGO to ensure rapid ion/electron transport. This “adsorption-catalysis-transport” collaborative mechanism enabled the Fe-VO 2- x /rGO cathode to achieve an ultrahigh capacity retention of 81.48% after 60,000 cycles at 20 A g −1 , surpassing state-of-the-art zinc-iodine systems. The work provides a paradigm for manipulating interfacial dynamics through electronic and crystallographic dual regulation in conversion-type batteries.
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Journal of Energy Chemistry
·
2025
·
IF 14.9
Xiaona Zhang,Zeyang Liu,Wenxuan Guo,Wei An,Zhaoyi Song,Yizhang Du,Tongjun Shen,Qihao Qin,Chunxia Wang,Guoyong Huang,Shengming Xu,Junjie Mao
The strong hydrogen binding affinity on Ru surfaces and their intrinsic aggregation tendency pose significant challenges to the hydrogen evolution reaction (HER) activity of Ru-based electrocatalysts. The construction of active electrocatalysts composed of partially dispersed nanoparticles (NPs) and individual single atomic sites with robust thermodynamic stability, has emerged as a viable alternative to benchmark commercial HER electrocatalyst. Herein, a multi-step strategy was designed to synthesize Ru NP @Fe SA -NC electrocatalyst and a robust interaction between uniformly dispersed Ru NPs and embedded single-atom Fe sites was uncovered, which not only regulates the particle size of Ru NPs but also controls the spin state and electronic configuration of Fe single atom. Moreover, magnetic characterization further corroborates the synergetic effect and predicts that the synergetic effect induces a high spin state of the Fe atom with unpaired electrons in the 3 d orbitals, which enhances the adsorption of intermediates and accelerates the reaction kinetics. The as obtained electrocatalyst demonstrate exceptional performance with a low overpotential of 13 mV at 10 mA cm -2 in alkaline condition. Remarkably, theoretical calculations indicates that the outstanding performance of Ru NP @Fe SA -NC stems from the Fe optimized electronic structure of the Ru site, which downshifts the d-band center, reduces the energy barriers for water dissociation and optimizes H* desorption, thereby promoting HER. This study presents an innovative approach to utilize Fe SA -NC to stabilize Ru NPs and reduce the energy barrier, contributing to an ideal HER performance.
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MOLECULES
·
2018
·Vol. 23
·期 4
·756
·
IF 3.098
Ming-Xia Song,Zhen-Yuan Wang,Shi-Hui He,Sheng-Wang Yu,Shi-Long Chen,Dong-Fu Guo,Wen-Hao Zhao,Xian-Qing Deng
In this study, a novel series of 4-(2-(alkylthio)benzo[d]oxazol-5-yl)-2,4-dihydro-3H-1,2,4-triazol-3-ones (4a–m) was designed and synthesized. The anticonvulsant activities of these compounds were evaluated by using the maximal electroshock seizure (MES) and subcutaneous pentylenetetrazole (scPTZ) seizure models in mice. The neurotoxicity of these compounds was evaluated using the rotarod neurotoxicity test. The majority of compounds showed anti-MES activities at 100 or 300 mg/kg. Compound4gwas considered to be the most promising, based on its potency against MES- and PTZ-induced seizures with ED50values of 23.7 and 18.9 mg/kg, respectively. The TD50value of4gwas 284.0 mg/kg, which resulted in a higher protective index (PI = TD50/ED50) value than that of carbamazepine and valproate. In an ELISA test, compound4gsignificantly increased the γ-aminobutyric acid (GABA) content in mouse brain. In addition, pretreatment with thiosemicarbazide (an inhibitor of the GABA synthesizing enzyme) significantly decreased the activity of4gin the MES model, which suggests that the mechanism through which compound4gelicits its anticonvulsive action is at least in part through increasing the GABA level in the brain.Keywords:anticonvulsant;maximal electroshock;pentylenetetrazole;benzoxazole;triazolone
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International Journal of Nanomedicine
·
2023
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IF 8
Hongzhi Qiao,Lihua Chen,Tianqi Rui,Jingxian Wang,Ting Chen,Tingming Fu,Junsong Li,Liuqing Di
Andrographolide (ADG) is a diterpenoid isolated from Andrographis paniculata with a wide spectrum of biological activities, including anti-inflammatory, anticancer and hepatoprotective effects. However, its poor water solubility and efflux by P-glycoprotein have resulted in lower bioavailability. In this study, ADG nanosuspensions (ADG-NS) were prepared using a wet media milling technique followed by freeze drying. d-α-Tocopheryl polyethylene glycol 1000 succinate (TPGS), a surfactant that inhibits P-glycoprotein function, and sodium lauryl sulfate were used as surface stabilizers. A Box–Behnken design was used to optimize the nanosuspension preparation. The products of these optimal preparation conditions were amorphous and possessed much faster dissolution in vitro than a coarse powder of ADG. The particle size and redispersibility index of the freeze-dried ADG-NS were 244.6±3.0 nm and 113%±1.14% (n=3), respectively. A short-term stability study indicated that the freeze-dried ADG-NS could remain highly stable as nanosuspensions during the testing period. A test of transport across a Caco-2 cell monolayer revealed that the membrane permeability (Papp) of ADG-NS was significantly higher than the permeability of the ADG coarse powder or ADG-NS without TPGS (P<0.01). Compared to the ADG coarse powder, a physical mixture, commercial dripping pills and ADG-NS without TPGS, ADG-NS exhibited significantly higher plasma exposure with significant enhancements in Cmax and area under the curve of plasma concentration versus time from zero to the last sampling time (AUC0−t) (P<0.01). An evaluation of the anti-inflammatory effect on Carr-induced paw edema demonstrated that the ADG-NS were more effective in reducing the rate of paw swelling, producing a greater increase in the serum levels of nitric oxide (NO), Interleukin-1 (IL-1) and tumor necrosis factor-α (TNF-α) (P<0.01) and an increase in superoxide dismutase activity (P<0.05) compared to the ADG coarse powder. This study indicated that nanosuspensions could act as an effective delivery device for ADG to enhance its oral bioavailability and biological efficacy.
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