The aim of this study is to investigate the molecular mechanism of licochalcone A (LCA) in alleviating abnormal gluconeogenesis and endoplasmic reticulum (ER) stress caused by type 2 diabetes mellitus (T2DM). In the in vivo study, 8-week-old male C57BL/6J mice were fed with a high-fat and high-sugar diet and injected intraperitoneally with streptozotocin (STZ) to establish a T2DM model. LCA (5 and 10 mg·kg^-1) was administered at an interval of 3 days for 3 weeks with metformin (MET, 200 mg·kg^-1) as a positive control drug. The animal experiment protocol was reviewed and approved by the Experimental Animal Ethics Committee of Beijing University of Chinese Medicine (approval number: BUCM-4-2021061701-2060). Human hepatoma cell line HepG2 was used as the experimental cell line for in vitro experiments. Sodium palmitate (SP) was used to induce the insulin resistance cell model and tunicamycin (TM) was applied to establish the ER stress cell model. Real-time quantitative polymerase chain reaction (RT-qPCR), enzyme-linked immunosorbent assay (ELISA) and Western blot (WB) were used to detect the mRNA and protein levels of gluconeogenesis and ER stress-related targets, respectively. Molecular docking and dynamics simulations were used to verify the interaction between LCA and key targets. The results showed that LCA inhibits gluconeogenesis by reducing phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6P) and increasing 6-phosphofructokinase-2/fructose-2,6-bisphosphatase 3 (PFKFB3) at both the mRNA and protein levels, as well as suppressing the activity of pyruvate carboxylase (PC). Additionally, LCA alleviates ER stress by downregulating the transcription of eukaryotic initiation factor 2 subunit α (eIF2α), inositol-requiring enzyme 1α (IRE1α), X-box binding protein 1 (XBP1), c-Jun N-terminal kinase 1 (JNK1), and activating transcription factor 6α (ATF6α), inhibiting the transcription and protein expression of glucose-regulated protein 78 (GRP78), and suppressing the phosphorylation of protein kinase RNA-like endoplasmic reticulum kinase (PERK). In conclusion, LCA alleviates abnormal gluconeogenesis and ER stress, thereby ameliorating the abnormal metabolism induced by T2DM.

Rheumatoid arthritis(RA), a chronic autoimmune disease, is featured by persistent joint inflammation. The development of RA is associated with the disturbance of endogenous metabolites and intestinal microbiota. Gardeniae Fructus(GF), one of the commonly used medicinal food in China, is usually prescribed for the prevention and treatment of jaundice, inflammation, ache, fever, and skin ulcers. GF exerts an effect on ameliorating RA, the mechanism of which remains to be studied. In this study, ultra-perfor-mance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS)-based serum non-target metabolomics and 16S rDNA high-throughput sequencing were employed to elucidate the mechanism of GF in ameliorating RA induced by complete Freund's adjuvant in rats. The results showed that GF alleviated the pathological conditions in adjuvant arthritis(AA) rats. The low-and high-dose GF lo-wered the serum levels of interleukin(IL)-6, tumor necrosis factor-α(TNF-α), IL-1β, and prostaglandin E2 in the rats(P<0.05, P<0.01). Pathways involved in metabolomics were mainly α-linolenic acid metabolism and glycerophospholipid metabolism. The results of 16S rDNA sequencing showed that the Streptococcus, Facklamia, Klebsiella, Enterococcus, and Kosakonia were the critical gut microorganisms for GF to treat AA in rats. Spearman correlation analysis showed that the three differential metabolites PE-NMe[18:1(9Z)/20:0], PC[20:1(11Z)/18:3(6Z,9Z,12Z)], and PC[20:0/18:4(6Z,9Z,12Z,15Z)] were correlated with the differential bacteria. In conclusion, GF may ameliorate RA by regulating the composition of intestinal microbiota, α-linolenic acid metabolism, and glycerophospholipid metabolism. The findings provide new ideas and data for elucidating the mechanism of GF in relieving RA.
Rats ; Animals ; Chromatography, Liquid ; Gardenia ; Tandem Mass Spectrometry ; Gastrointestinal Microbiome ; alpha-Linolenic Acid ; Metabolomics/methods* ; Arthritis, Rheumatoid/drug therapy* ; Inflammation ; Glycerophospholipids

The formulation and revision of the detection methods of indoor air quality standards is an important, rigorous and delicate endeavor. This paper introduced the formulation and revision of the detection methods of the standards for indoor air quality (GB/T 18883-2022), focusing on the revision process, revision principles, main adjustments and technical points of some key indicators to facilitate users to better understand and apply the detection methods in standards for indoor air quality (GB/T 18883-2022).
Humans ; Air Pollution, Indoor ; China ; Reference Standards ; Air Pollutants/analysis*

The formulation and revision of the detection methods of indoor air quality standards is an important, rigorous and delicate endeavor. This paper introduced the formulation and revision of the detection methods of the standards for indoor air quality (GB/T 18883-2022), focusing on the revision process, revision principles, main adjustments and technical points of some key indicators to facilitate users to better understand and apply the detection methods in standards for indoor air quality (GB/T 18883-2022).
Humans ; Air Pollution, Indoor ; China ; Reference Standards ; Air Pollutants/analysis*

Precious Tibetan medicine formula is a characteristic type of medicine commonly used in the clinical treatment of central nervous system diseases. Through the summary of modern research on the precious Tibetan medicine formulas such as Ratnasampil, Ershiwuwei Zhenzhu Pills, Ershiwewei Shanhu Pills, and Ruyi Zhenbao Pills, it is found that they have obvious advantages in the treatment of stroke, Alzheimer's disease, epilepsy, angioneurotic headache, and vascular dementia. Modern pharmacological studies have shown that the mechanisms of precious Tibetan medicine formulas in improving central nervous system diseases are that they promote microcirculation of brain tissue, regulate the permeability of the blood-brain barrier, alleviate inflammation, relieve oxidative stress damage, and inhibit nerve cell apoptosis. This review summarizes the clinical and pharmacological studies on precious Tibetan medicine formulas in prevention and treatment of central nervous system diseases, aiming to provide a reference for future in-depth research and innovative discovery of Tibetan medicine against central nervous diseases.
Blood-Brain Barrier ; Brain ; Central Nervous System Diseases ; Humans ; Medicine, Tibetan Traditional ; Stroke/drug therapy*

The present study investigated the mechanism of the Tibetan medicine Ershiwuwei Songshi Pills(ESP) against the liver injury induced by acetaminophen(APAP) in mice based on the kelch-like ECH-associated protein 1(Keap1)/nuclear transcription factor E2 related factor 2(Nrf2) and Toll-like receptor 4(TLR4)/nuclear factor-kappa B(NF-κB) p65 signaling pathways. Kunming mice were randomly divided into a blank control group, a model group, an N-acetyl-L-cysteine(NAC) group, and high-(400 mg·kg~(-1)), medium-(200 mg·kg~(-1)), and low-dose(100 mg·kg~(-1)) ESP groups. After 14 days of continuous administration, except for those in the control group, the mice were intraperitoneally injected with 200 mg·kg~(-1) APAP. After 12 h, the serum and liver tissues of mice were collected. Hematoxylin-eosin(HE) staining was performed on pathological sections of the liver, and the levels of aspartate aminotransferase(AST) and alanine aminotransferase(ALT) in the serum and the levels of glutathione(GSH), malondialdehyde(MDA), superoxide dismutase(SOD), catalase(CAT), myeloperoxidase(MPO), and total antioxidant capacity(T-AOC) in liver tissue homogenate were detected to observe and analyze the protective effect of ESP on APAP-induced liver injury in mice. The serum levels of tumor necrosis factor-alpha(TNF-α), interleukin-1 beta(IL-1β), and interleukin-6(IL-6) were determined by enzyme-linked immunosorbent assay(ELISA). The protein expression of Nrf2, Keap1, TLR4, and NF-κB p65 in the liver was determined by Western blot. Quantitative real-time was used to determine the mRNA expression of glutamate-cysteine ligase catalytic subunit(GCLC), glutamate-cysteine ligase regulatory subunit(GCLM), heme oxygenase-1(HO-1), and NAD(P)H dehydrogenase quinone 1(NQO-1) in the liver to explore the mechanism of ESP in improving APAP-induced liver damage in mice. As revealed by results, compared with the model group, the ESP groups showed improved liver pathological damage, decreased ALT and AST levels in the serum and MDA and MPO content in the liver, increased GSH, SOD, CAT, and T-AOC in the liver, reduced TNF-α and IL-6 levels in the serum, down-regulated expression of Keap1 in the liver cytoplasm and NF-κB p65 in the liver nucleus, up-regulated expression of Nrf2 in the liver nucleus, insignificant change in TLR4 expression, and elevated relative mRNA expression levels of antioxidant genes GCLC, GCLM, HO-1, and NQO-1. ESP can reduce the oxidative damage and inflammation caused by APAP, and the mechanism may be related to the Keap1/Nrf2 signaling pathway and the signal transduction factors on the TLR4/NF-κB p65 pathway.
Acetaminophen/toxicity* ; Animals ; Antioxidants/pharmacology* ; Glutamate-Cysteine Ligase/pharmacology* ; Glutathione ; Interleukin-6/metabolism* ; Kelch-Like ECH-Associated Protein 1/metabolism* ; Liver ; Medicine, Tibetan Traditional ; Mice ; NF-E2-Related Factor 2/metabolism* ; NF-kappa B/metabolism* ; RNA, Messenger/metabolism* ; Signal Transduction ; Superoxide Dismutase/metabolism* ; Toll-Like Receptor 4/metabolism* ; Tumor Necrosis Factor-alpha/metabolism*

The present study investigated the mechanism of the Tibetan patent medicine Ershiwuwei Shanhu Pills(ESP) in alleviating Alzheimer's disease in mice via Akt/mTOR/GSK-3β signaling pathway. BALB/c mice were randomly assigned into a blank control group, a model group, low(200 mg·kg~(-1)), medium(400 mg·kg~(-1)) and high(800 mg·kg~(-1)) dose groups of ESP, and donepezil hydrochloride group. Except the blank control group, the other groups were given 20 mg·kg~(-1) aluminum chloride by gavage and 120 mg·kg~(-1) D-galactose by intraperitoneal injection for 56 days to establish Alzheimer's disease model. Morris water maze was used to detect the learning and memory ability of mice. The level of p-tau protein in mouse hippocampus and the levels of superoxide dismutase(SOD), malondialdehyde(MDA), catalase(CAT), and total antioxidant capacity(T-AOC) in hippocampus and serum were detected. Hematoxylin-eosin staining and Nissl staining were performed for the pathological observation of whole brain in mice. TdT-mediated dUTP nick-end labeling(TUNEL) staining was employed for the observation of apoptosis in mouse cortex. Western blot was adopted to detect the protein levels of p-mTOR, p-Akt, and GSK-3β in the hippocampus. Compared with the model group, the ESP groups showcased alleviated pathological damage of the whole brain, decreased TUNEL positive cells, reduced level of p-tau protein in hippocampus, and risen SOD, CAT, and T-AOC levels and declined MDA level in hippocampus and serum. Furthermore, the ESP groups had up-regulated protein levels of p-mTOR and p-Akt while down-regulated protein level of GSK-3β in hippocampus. Therefore, ESP can alleviate the learning and memory decline and oxidative damage in mice with Alzheimer's disease induced by D-galactose combined with aluminum chloride, which may be related to Akt/mTOR/GSK-3β signaling pathway.
Aluminum Chloride/adverse effects* ; Alzheimer Disease/drug therapy* ; Animals ; Galactose/metabolism* ; Glycogen Synthase Kinase 3 beta/metabolism* ; Hippocampus/metabolism* ; Mice ; Mice, Inbred BALB C ; Plant Extracts ; Proto-Oncogene Proteins c-akt/metabolism* ; Signal Transduction ; Superoxide Dismutase/metabolism* ; TOR Serine-Threonine Kinases/metabolism* ; tau Proteins

This study aims to investigate the mechanism of the Tibetan medicine Ershiwuwei Shanhu Pills(ESP) in improving scopolamine-induced learning and memory impairment in mice based on Keap1/Nrf2/HO-1 signaling pathway. ICR mice were randomized into blank group, model group, low-dose(200 mg·kg~(-1)), medium-dose(400 mg·kg~(-1)), and high-dose(800 mg·kg~(-1)) ESP groups, and donepezil hydrochloride group. The learning and memory impairment was induced in mice by intraperitoneal injection of scopola-mine. The learning and memory abilities of mice were detected by Morris water maze test, and the damage of hippocampal neurons and cortical neurons was detected based on Nissl staining. The expression of neuron specific nuclear protein(NeuN) in hippocampus and cortex of mice was determined by immunofluorescence assay, and the content of acetylcholine(Ach) and the activity of acetylcholines-terase(AchE) in hippocampus of mice by kits. Moreover, the content of superoxide dismutase(SOD), malondialdehyde(MDA), catalase(CAT), and total antioxidant capacity(T-AOC) in serum of mice was detected. The content of Kelch-like ECH-associated protein 1(Keap1), nuclear factor erythroid 2-related factor 2(Nrf2), and heme oxygenase 1(HO-1) in hippocampus was determined by Western blot. The results showed that there were significant differences in the trajectory map of mice among different groups in the behavioral experiment. Moreover, the latency of ESP groups decreased significantly compared with that in the model group. The hippocampal neurons in the high-dose ESP group were significantly more than those in the model group and the cortical neurons in the high-dose and medium-dose ESP groups were significantly more than those in the model group. The expression of NeuN in the model group was significantly decreased compared with that in the blank group, and the expression in the ESP groups was significantly higher than that in the model group. The AchE activity and MDA level were significantly decreased, and Ach content and levels of SOD, CAT, and T-AOC in the ESP groups were significantly increased in the ESP groups compared with those in the model group. The expression of Keap1 in the model group was significantly increased compared with that in the blank group, and the Keap1 expression increased insignificantly in ESP groups compared with that in the model group. The expression of Nrf2 and HO-1 was significantly lower in the model group than in the blank group, and the expression was significantly higher in the medium-dose ESP group than in the model group. In conclusion, ESP protected mice against the scopolamine-induced learning and memory impairment by regulating the Keap1/Nrf2/HO-1 signaling pathway.
Animals ; Kelch-Like ECH-Associated Protein 1/metabolism* ; Medicine, Tibetan Traditional ; Mice ; Mice, Inbred ICR ; NF-E2-Related Factor 2/metabolism* ; Oxidative Stress ; Plant Extracts ; Scopolamine/adverse effects* ; Signal Transduction ; Superoxide Dismutase/metabolism*

The reconstruction of tactile function during the repair of skin damage caused by factors including burns is inseparable from the functional regeneration of tactile receptor Merkel cells. Merkel cells mainly exist in the basal layer of the epidermis and are closely connected with nerves to form Merkel cell-nerve complexes, which play an important role in biological organisms. A large number of studies have shown that Merkel cells conduct precise transmission of mechanical force stimuli through the mechanically gated ion channels PIEZO2, and perform the function of tactile receptors. In this paper, we discussed the characteristics of Merkel cells and analyzed the different subgroups that may possibly exist in this type of cells and their functions, at the same time, we investigated the animal model research of touch-related diseases and the clinical diseases related to touch, revealing the importance of Merkel cell function research.
Animals ; Ion Channels/metabolism* ; Mechanotransduction, Cellular/physiology* ; Merkel Cells/physiology* ; Skin/metabolism* ; Touch/physiology*

OBJECTIVE: To evaluate the consistency and reproducibility of aortic root measurements by Anythink, a semi-automated preoperative CT analysis software, with those of 3mensio. METHODS: Sixty-seven patients undergoing transcatheter aortic valve replacement (TAVR) in the First Medical Center of Chinese PLA General Hospital from December, 2016 to February, 2022 were retrospectively enrolled in this study. A cardiology resident who completed his professional training used both the software Anythink and 3mensio (as the gold standard) to reconstruct the aortic root model and analyze the parameters of the aortic annulus and the surrounding structures. The correlation and consistency of the measurement results of two software were analyzed. Two independent residents also used Anythink software to repeat the measurements for the same patient for assessment of the reproducibility of Anythink measurements. The valve models were selected based on the measurements by Anythink and 3mensio, and similarities and differences of the two software in clinical valve selection were assessed. RESULTS: The measurements of the distances from the anulus plane to the left and right coronary ostium, average diameter of the anulus, anulus area, anulus perimeter, and the angle between the annulus and horizontal plane did not differ significantly between the two software (P > 0.05), and their measurements showed positive correlations (r= 0.884-0.981, P < 0.01). The intra-group and inter-group correlation coefficients of the anulus parameters measured by Anythink ranged from 0.894 to 0.992 and from 0.651 to 0.954, respectively. The Kappa-test values of valve models selected by Anythink and 3mensio based on the average diameter, area diameter and perimeter diameter were 0.886, 0.796 and 0.775, respectively. The intra-group Kappa values for the valve models selected based on Anythink measurements were 0.819, 0.841, and 0.795, and the inter-group Kappa values were 0.812, 0.812, and 0.768, respectively. Compared with the measurements by 3mensio, the recommended area diameter measured by Anythink was slightly greater in patients with postoperative paravalvular leakage, but slightly smaller in patients with postoperative new-onset conduction block. CONCLUSION Anythink has excellent measurement consistency and high reproducibility for aortic root measurements, and trained cardiologists can use Anythink to obtain accurate aortic root parameters before TAVR.
Humans ; Transcatheter Aortic Valve Replacement ; Reproducibility of Results ; Retrospective Studies ; Aorta ; Tomography, X-Ray Computed