Systematic review and meta-analysis of repetitive transcranial magnetic stimulation (rTMS) for activities of daily living in Alzheimer's disease.

OBJECTIVE: This systematic review of randomised controlled trials (RCTs) was conducted to assess the effect of repetitive transcranial magnetic stimulation (rTMS) on activities of daily living (ADLs) in Alzheimer's disease (AD) patients. DATA SOURCES: Ten databases were retrieved for pertinent Chinese and English literatures published up until January 2024. REVIEW METHODS: All RCTs of rTMS for ADLs in AD were included in this meta-analysis. Two researchers independently selected the literatures, retrieved the data of included literatures, accessed risk-of-bias of literatures with the Cochrane Collaboration's quality criteria and then cross-checked. Meta-analysis was carried out with Cochrane's Review Manager (RevMan, version 5.4). The PRISMA guidelines were followed in this systematic review. RESULTS: The 37 literatures involving 2461 patients with AD were included in this study. Compared with the control groups received the interventions such as routine pharmacotherapy, cognitive training, ect., with/without sham-rTMS, the experiment groups received the interventions of the control groups and rTMS. The findings were as follows: ADL scale [mean difference (MD) = -3.92, 95%CI (-4.93, -2.91), P < 0.00001]; Barthel Index (BI) [MD = 9.75, 95% CI (6.66, 12.85), P < 0.00001]; Modified Barthel Index (MBI) [MD = 5.43, 95% CI (3.13, 7.73), P < 0.00001]. The differences were statistically significant for all indicators. In 29 studies, rTMS stimulation sites were located in the dorsolateral prefrontal cortex (DLPFC). CONCLUSION: The rTMS could improve the ADLs in AD patients, and the DLPFC was a frequently used stimulation site of the rTMS for AD treatment.

High-frequency repetitive transcranial magnetic stimulation (HF-rTMS) on global cognitive function of elderly in mild to moderate Alzheimer's disease: a systematic review and meta-analysis.

OBJECTIVE: High-frequency repetitive transcranial magnetic stimulation (HF-rTMS) is a non-invasive brain stimulation technique used to improve cognitive deficits in patients with Alzheimer's disease (AD). This systematic review and meta-analysis aimed to evaluate the efficacy of HF-rTMS in improving global cognitive function rehabilitation in elderly patients with mild to moderate AD. METHODS: A detailed literature search of publications using ten databases (Chinese: Wanfang, VIP Periodical, SinoMed, the Chinese National Knowledge Infrastructure; English: PubMed, Embase, OVID, Web of Science, Cochrane Library, and EBSCOhost) was performed to identify English and Chinese language articles published up to December 2022. We only included randomized controlled trials (RCTs) that evaluate the effect of HF-rTMS on elderly patients with mild to moderate AD. The retrieved studies were carefully reviewed, extracted data, and assessed quality. RESULTS: Seventeen studies, including 1161 elderly patients with mild to moderate AD, were included in this meta-analysis. Compared to the control group, HF-rTMS could increase MMSE (mean difference [MD] = 3.64; 95%CI 1.86-5.42; P < 0.0001), MoCA (MD = 3.69; 95%CI 1.84-5.54; P < 0.0001), P300 amplitude (MD = 1.09; 95%CI 0.45-1.72; P = 0.0008), and total effective rate scores (MD = 3.64; 95% CI 2.14-6.18; P < 0.00001) while decreasing ADAS-Cog (MD = - 3.53; 95%CI - 4.91- - 2.15; P < 0.00001) and P300 latency scores (MD = - 38.32; 95%CI - 72.40- - 4.24; P = 0.03). Our study showed that HF-rTMS could improve the global cognitive function of elderly patients with mild to moderate AD. CONCLUSION: HF-rTMS can improve global cognitive function in elderly patients with mild to moderate AD, which is an effective and safe rehabilitation treatment tool for AD patients.

Systematic review and meta-analysis of transcranial direct current stimulation (tDCS) for global cognition in mild cognitive impairment and Alzheimer's disease.

OBJECTIVE: To systematically assess the effectiveness of transcranial direct current stimulation (tDCS) on global cognition in patients with mild cognitive impairment (MCI) and Alzheimer's disease (AD). DATA SOURCES: Ten databases were retrieved for pertinent Chinese and English studies published up until February 2023. DATA EXTRACTION: Two researchers independently selected the literature, extracted the data, evaluated using the Cochrane Collaboration's quality criteria, and then cross-checked. Meta-analysis was performed using RevMan 5.4. RESULTS: 22 studies involving 1074 patients were included. Compared with the control group received the interventions such as pharmacotherapy, cognitive stimulation, et al., with/without sham-tDCS, while the experiment group received tDCS added to the interventions of the control group. The meta-analysis found that tDCS increased MMSE, MoCA, MODA scores and reduced the P300 latency scores (all P < 0.05). CONCLUSION: The tDCS can ameliorate the global cognition of patients with MCI and AD, and it has a better rehabilitation effect than non-tDCS or sham-tDCS.

Influence of growth interruption on the morphology and luminescence properties of AlGaN/GaN ultraviolet multi-quantum wells.

The influence of growth interruption on the surface and luminescence properties of AlGaN/GaN ultraviolet multi-quantum wells (UV MQWs) is investigated. It is found that when the well and barrier layers of MQW samples are continuously grown at the same temperature, they have lower edge dislocation density and flatter surface of MQWs compared to samples with interrupted well and barrier growth. Moreover, continuous growth of well and barrier layers is more conducive to improving the luminescence efficiency of MQWs. This phenomenon is attributed to more impurity incorporation induced by the growth interruption, while a continuous growth of well and barrier can reduce surface diffusion and migration processes of atoms, reducing the defects and surface roughness of MQWs. In addition, the continuous growth of well and barrier can better control the reaction between Al and N atoms, avoiding the formation of excessively high Al content AlGaN at the well/barrier interface, thus improving the luminescence of UV MQWs.

High-frequency repetitive transcranial magnetic stimulation (HF-rTMS) impacts activities of daily living of patients with post-stroke cognitive impairment: a systematic review and meta-analysis.

OBJECTIVE: To systematically evaluate the impact of high-frequency repetitive transcranial magnetic stimulation (HF-rTMS) on activities of daily living (ADLs) of patients with post-stroke cognitive impairment (PSCI). DATA SOURCES: Relevant studies published as of November 2022 (English and Chinese) were searched in Web of Science, PubMed, Embase, Cochrane Library, OVID, China Science and Technology Journal Database (VIP), Wanfang, Chinese National Knowledge Infrastructure (CNKI), and SinoMed databases. REVIEW METHODS: Randomized controlled trials (RCTs) that used HF-rTMS for the treatment of ADLs in patients with PSCI were included in this meta-analysis. Two reviewers independently screened literature, extracted the data, evaluated the risk of bias using the Cochrane Risk of Bias Tool, and cross-checked. RESULTS: Forty-one RCTs involving 2855 patients with PSCI were included. In 30 RCTs, the experimental group received HF-rTMS in addition to the interventions used in the control group. In 11 RCTs, the experimental group received HF-rTMS while the control group received sham-rTMS. Barthel Index (BI), Modified Barthel Index (MBI), and Functional Independence Measure (FIM) were higher in the HF-rTMS group than in the control group, whereas scores of Blessed Behavior Scale was lower in the HF-rTMS group than in the control group. All P < 0.05. In 36 studies, the stimulation sites were on the dorsolateral prefrontal cortex (DLPFC). CONCLUSION: HF-rTMS can ameliorate ADLs of patients with PSCI and has a better rehabilitation effect on PSCI.

Stepped upper waveguide layer for higher hole injection efficiency in GaN-based laser diodes.

We propose a stepped upper waveguide layer (UWG) to improve the hole injection efficiency of GaN-based laser diodes (LDs), and investigate its effect on the performance of LDs from experiments and theoretical calculations. The experimental characterization of the LD with stepped UWG presents a decrease of 16.6% for the threshold current as well as an increase of 41.2% for the slope efficiency compared to the LD with conventional GaN UWG. Meanwhile, strong localized effects are found in the quantum wells of LD with stepped UWG and a large blue-shift in the electroluminescence (EL) spectra below the threshold by analyzing the differential efficiency and the EL spectra. The large blue shift implies a stronger polarization field in the LDs, which may affect the injection of holes. Additionally, the simulation results demonstrate that the LD with stepped UWG achieves higher hole injection efficiency by modulating the valence band, and the hole current density injected into the quantum wells reaches 6067 A/cm2.

Brachial plexus injury after clavicle fracture operation: a case report and literature review.

BACKGROUND: Open reduction and internal fixation (ORIF) is the preferred choice for treating clavicle fractures. The brachial plexus injury caused by ORIF of a clavicle fracture is very rare. If it is not treated in time, the function of the brachial plexus will be challenging to recover, which will eventually lead to upper limb dysfunction and seriously affect the patient's quality of life. Our team recently used ORIF to treat a patient with a clavicle fracture, who developed brachial plexus injury symptoms after surgery. CASE PRESENTATION: A 34-year-old female patient was admitted to the hospital for 13 h due to the right shoulder movement restriction after a fall. Due to the significant displacement of the fracture, we used ORIF to treat the fracture. The surgery went well. When the anaesthesia effect subsided 12 h after the operation, the patient developed right brachial plexus injury symptoms, decreased right upper limb muscle strength, dysfunction, and hypoesthesia. Symptomatic treatments, such as nourishing nerve and electrical stimulation, were given immediately. Sixty days after the operation, the patient's brachial plexus injury symptoms disappeared, and the function of the right upper limb returned to the preoperative state. CONCLUSIONS: Patients with clavicle fractures usually need to undergo a careful physical examination before surgery to determine whether symptoms of brachial plexus injury have occurred. Anaesthesia puncture requires ultrasound guidance to avoid direct damage to the brachial plexus. When the fracture end is sharp, reset should be careful to prevent nerve stump stabbed. When using an electric drill to drill holes, a depth limiter should be installed in advance to prevent the drill from damaging the subclavian nerve and blood vessels. When measuring the screw depth, the measuring instrument should be close to the bone surface and sink slowly to avoid intense hooks and damage to the brachial plexus. Try to avoid unipolar electrosurgical units to prevent heat conduction from damaging nerves, and bipolar electrocoagulation should be used instead. If symptoms of brachial plexus injury occur after surgery, initial symptomatic treatment is drugs and functional exercise, and if necessary, perform surgical exploration.

MicroRNA hsa-miR-1301-3p Regulates Human ADH6, ALDH5A1 and ALDH8A1 in the Ethanol-Acetaldehyde-Acetate Metabolic Pathway.

Alcohol dehydrogenases (ADHs) and aldehyde dehydrogenases (ALDHs) are vital enzymes involved in the metabolism of a variety of alcohols. Differences in the expression and enzymatic activity of human ADHs and ALDHs correlate with individual variability in metabolizing alcohols and drugs and in the susceptibility to alcoholic liver disease. MicroRNAs (miRNAs) function as epigenetic modulators to regulate the expression of drug-metabolizing enzymes. To characterize miRNAs that target ADHs and ALDHs in human liver cells, we carried out a systematic bioinformatics analysis to analyze free energies of the interaction between miRNAs and their cognate sequences in ADH and ALDH transcripts and then calculated expression correlations between miRNAs and their targeting ADH and ALDH genes using a public data base. Candidate miRNAs were selected to evaluate bioinformatic predictions using a series of biochemical assays. Our results showed that 11 miRNAs have the potential to modulate the expression of two ADH and seven ALDH genes in the human liver. We found that hsa-miR-1301-3p suppressed the expression of ADH6, ALDH5A1, and ALDH8A1 in liver cells and blocked their induction by ethanol. In summary, our results revealed that hsa-miR-1301-3p plays an important role in ethanol metabolism by regulating ADH and ALDH gene expression. SIGNIFICANCE STATEMENT: Systematic bioinformatics analysis showed that 11 microRNAs might play regulatory roles in the expression of two alcohol dehydrogenase (ADH) and seven aldehyde dehydrogenase (ALDH) genes in the human liver. Experimental evidences proved that hsa-miR-1301-3p suppressed the expression of ADH6, ALDH5A1, and ALDH8A1 in liver cells and decreased their inducibility by ethanol.

CYC31, A Natural Bromophenol PTP1B Inhibitor, Activates Insulin Signaling and Improves Long Chain-Fatty Acid Oxidation in C2C12 Myotubes.

3-bromo-4,5-Bis(2,3-dibromo-4,5-dihydroxybenzyl)-1,2-benzenediol (CYC31) is a bromophenol protein tyrosine phosphatase 1B (PTP1B) inhibitor isolated from the red alga Rhodomela confervoides. Here, the effect of CYC31 on the insulin signaling and fatty-acid-induced disorders in C2C12 myotubes was investigated. Molecular docking assay showed that CYC31 was embedded into the catalytic pocket of PTP1B. A cellular study found that CYC31 increased the activity of insulin signaling and promoted 2-NBDG uptake through GLUT4 translocation in C2C12 myotubes. Further studies showed that CYC31 ameliorated palmitate-induced insulin resistance in C2C12 myotubes. Moreover, CYC31 treatment significantly increased the mRNA expression of carnitine palmitoyltransferase 1B (CPT-1B) and fatty acid binding protein 3 (FABP3), which was tightly linked with fatty acid oxidation. These findings suggested that CYC31 could prevent palmitate-induce insulin resistance and could improve fatty acid oxidation through PTP1B inhibition.

Integration of proteomics, lipidomics, and metabolomics reveals novel metabolic mechanisms underlying N, N-dimethylformamide induced hepatotoxicity.

N, N-Dimethylformamide (DMF) is a universal organic solvent which widely used in various industries, and a considerable amount of DMF is detected in industrial effluents. Accumulating animal and epidemiological studies have identified liver injury as an early toxic effect of DMF exposure; however, the detailed mechanisms remain poorly understood. In this study, we systematically integrated the quantitative proteomics, lipidomics, and metabolomics data obtained from the primary human hepatocytes exposed to DMF, to depict the complicated biochemical reactions correlated to liver damage. Eventually, we identified 284 deregulated proteins (221 downregulated and 63 upregulated) and 149 deregulated lipids or metabolites (99 downregulated and 50 upregulated) induced by DMF exposure. Further, the integration of the protein-metabolite (lipid) interactions revealed that N-glycan biosynthesis (involved in the endoplasmic reticulum stress and the unfolded protein response), bile acid metabolism (involved in the lipid metabolism and the inflammatory process), and mitochondrial dysfunction and glutathione depletion (both contributed to reactive oxygen species) were the typical biochemical reactions disturbed by DMF exposure. In summary, our study identified the versatile protein, lipid, and metabolite molecules in multiple signaling and metabolic pathways involved in DMF induced liver injury, and provided new insights to elucidate the toxic mechanisms of DMF.

Hyaluronic Acid Coated Acid-Sensitive Nanoparticles for Targeted Therapy of Adjuvant-Induced Arthritis in Rats.

Activated macrophages play a vital role in rheumatoid arthritis (RA) pathophysiology. CD44 is an overexpressed receptor on activated macrophages that is a potential target site for RA treatment. In this study, we prepared hyaluronic acid (HA) coated acid-sensitive polymeric nanoparticles (HAPNPs) composed of egg phosphatidylcholine, polyethylenimine, and poly (cyclohexane-1,4-diyl acetone dimethylene ketal) (PCADK) loaded with dexamethasone (Dex) for the treatment of RA. PCADK was used to form polymeric cores because of its acid-sensitivity. The HAPNPs were about 150 nm in size and had a zeta potential of -2.84 mV. The release rate of Dex from HAPNPs/Dex in vitro increased markedly when the pH decreased from 7.4 to 4.5, indicating that the HAPNPs were pH-sensitive. In a cellular uptake study, stronger fluorescence signals were observed in activated macrophages treated with HAPNPs, suggesting that HAPNPs could be effective nanodevices target to activated macrophages. In rats with adjuvant-induced arthritis, HAPNPs could inhibited the progression of RA. Taken together, these results suggest that the HAPNPs could be useful in RA therapy.

Bioactive spirans and other constituents from the leaves of Cannabis sativa f. sativa.

In this paper, 17 compounds (1-17) were isolated from the leaves of Hemp (Cannabis sativa f. sativa). Among the isolates, two were determined to be new spirans: cannabispirketal (1), and α-cannabispiranol 4'-O-ß-D-glucopyranose (2) by 1D and 2D NMR spectroscopy, LC-MS, and HRESIMS. The known compounds 7, 8, 10, 13, 15, and 16 were isolated from Hemp (C. sativa f. sativa) for the first time. Furthermore, compounds 8 and 13 were isolated from the nature for the first time. All isolated compounds were evaluated for cytotoxicity on different tissue-derived passage cancer cell lines through cell viability and apoptosis assay. Among these compounds, compounds 5, 9 and 16 exhibited a broad-spectrum antitumor effect via inhibiting cell proliferation and promoting apoptosis. These results obtained have provided valuable clues to the understanding of the cytotoxic profile for these isolated compounds from Hemp (C. sativa f. sativa).

The role of lysosome in cell death regulation.

Lysosome is a highly membrane-bound organelle which possesses a sequence of biological functions including protein degradation, cell signal transduction, plasma membrane repairment, homoeostasis, and autophagy. The lysosome contains more than 50 soluble acid hydrolases, and the acidification of lysosome is the most important biological characteristic. The integrity of lysosome is of vital importance. During the past few years, it was reported that the destabilization of lysosomal membrane can result in the release of lysosomal contents into cytosol and trigger cell death in a caspase-dependent or caspase-independent pathway. Lysosome functions at the late stage of autophagy and degrades cellular components delivered by autophagosome, which is a complicated process. The present article will summarize the current knowledge on the role of lysosome in cell death regulation and the underlying mechanisms.

Moxibustion Promoted Axonal Regeneration and Improved Learning and Memory of Post-stroke Cognitive Impairment by Regulating PI3K/AKt and TACC3.

BACKGROUND: This study aimed to investigate whether moxibustion could affect PI3K/Akt pathway to regulate Transforming acidic coiled-coil containing protein 3 (TACC3) and promote axonal regeneration to improve learning and memory function in middle cerebral artery occlusion (MCAO) rats. METHODS: Sixty SD rats were randomly divided into 4 groups: sham-operated control group (SC), model control group (MC), model + moxibustion group (MM), and model + inhibitor + moxibustion group (MIM). The rats in MC, MM, and MIM groups were made into MCAO models, and PI3K inhibitor LY294002 was injected into the rats in MIM group before modeling; while the rats in SC group were only treated with artery separation without monofilament inserting. After that, the rats in MM and MIM groups were intervented with moxibustion. We used the Zea-Longa scale, micro-Magnetic Resonance Imaging (micro-MRI), Morris water maze (MWM), TUNEL, western blot (WB), immunofluorescence and immunohistochemistry to evaluate the neurological deficits, cerebral infarct volume, learning and memory, apoptotic cell percentage in the hippocampal, the expression level of axonal regeneration and PI3K/AKt related proteins, the expression level of TACC3. The detection of 2 h after surgery showed the result before moxibustion and 7 days after the intervention showed the results after moxibustion. RESULTS: After 7 d of intervention, the scores of Zea-Longa and the cerebral infarct volume, the escape latency, the percentage of apoptosis cells of MM group were lower than that of MC and MIM groups; the frequency of rats crossed the previous platform location, PI3K, p-Akt/t-Akt and TACC3, the level of GAP-43 in MM group was more than MC and MIM groups (P < 0.05). While no statistical difference existed between MIM group and MC group (P > 0.05). CONCLUSION: Moxibustion can promote axonal regeneration and improve learning and memory of Post-stroke cognitive impairment via activating the PI3K/AKT signaling pathway and TACC3.

High-Frequency Repetitive Transcranial Magnetic Stimulation on Overall Cognition in Patients With Poststroke Cognitive Impairment: A Systematic Review and Meta-analysis.

OBJECTIVE: The aim of the study is to comprehensively assess the recovery effects of high-frequency repetitive transcranial magnetic stimulation in patients with poststroke cognitive impairment. METHODS: Six English and four Chinese databases were searched for relevant studies published up to January 2022. Randomized controlled trials of patients with poststroke cognitive impairment treated with high-frequency repetitive transcranial magnetic stimulation were included. Included studies were assessed for the risk of bias through the Cochrane Intervention Systematic Review Manual 5.1.0. The meta-analysis was performed using RevMan 5.4 software. The PRISMA 2020 guidelines were followed. RESULTS: Sixty-one randomized controlled trials (4012 patients) were included. Montreal Cognitive Assessment Score, Mini-Mental State Examination score, event-related potential P300 (P300) amplitude, Loewenstein Occupational Therapy Cognitive Assessment score, and total effective rate of cognitive function were higher in the high-frequency repetitive transcranial magnetic stimulation group than in the control group at the end of the treatment period, and scores of Alzheimer Disease Assessment Scale-Cognitive Subscale and P300 latency were lower in the high-frequency repetitive transcranial magnetic stimulation group than in the control group. Fifty studies had selected the dorsolateral prefrontal cortex as the stimulation site for high-frequency repetitive transcranial magnetic stimulation. CONCLUSIONS: Compared with nonrepetitive transcranial magnetic stimulation or sham repetitive transcranial magnetic stimulation, high-frequency repetitive transcranial magnetic stimulation not only improves the overall cognitive function of poststroke cognitive impairment patients but also has better rehabilitation results.

Controlling GaN-Based Laser Diode Performance by Variation of the Al Content of an Inserted AlGaN Electron Blocking Layer.

The leakage of the electronic current of a laser diode (LD) has some significant influences on the performance of the LD. In this study, commercial simulation software LASTIP is used to numerically evaluate the performances of LDs by using different wavelengths and Al contents of the electron blocking layer (EBL). These LDs a adopt multilayer structure, which contains cladding layers, waveguide layers, multiple quantum well layers, contact layers and an AlxGa1-xN EBL. The influence mechanism of EBL is theoretically examined by analyzing the simulated performances. It is found that for short-wavelength violet LDs, the electrical and optical properties of the LD will reach the optimum state when the Al content (x) in the EBL is nearly 0.25. For long-wavelength green LDs, it will achieve optimum electrical and optical properties when the Al content in the EBL is as low as possible. We also compare the simulation results of LDs with emission wavelengths in the range of violet and green, including blue cyan, for a more general evaluation. According to the simulated results, it is verified that the influence of the EBL's Al content on LD performance enhances as the wavelength increases.

Magnetic Soft Catheter Robot System for Minimally Invasive Treatments of Articular Cartilage Defects.

Articular cartilage defects are among the most common orthopedic diseases, which seriously affect patients' health and daily activities, without prompt treatment. The repair biocarrier-based treatment has shown great promise. Total joint injection and open surgery are two main methods to deliver functional repair biocarriers into the knee joint. However, the exhibited drawbacks of these methods hinder their utility. The repair effect of total joint injection is unstable due to the low targeting rate of the repair biocarriers, whereas open surgery causes serious trauma to patients, thereby prolonging the postoperative healing time. In this study, we develop a magnetic soft catheter robot (MSCR) system to perform precise in situ repair of articular cartilage defects with minimal incision. The MSCR processes a size of millimeters, allowing it to enter the joint cavity through a tiny skin incision to reduce postoperative trauma. Meanwhile, a hybrid control strategy combining neural network and visual servo is applied to sequentially complete the coarse and fine positioning of the MSCR on the cartilage defect sites. After reaching the target, the photosensitive hydrogel is injected and anchored into the defect sites through the MSCR, ultimately completing the in situ cartilage repair. The in vitro and ex vivo experiments were conducted on a 3D printed human femur model and an isolated porcine femur, respectively, to demonstrate the potential of our system for the articular cartilage repair.

Explore the active ingredients and potential mechanism of action on Actinidia arguta leaves against T2DM by integration of serum pharmacochemistry and network pharmacology.

BACKGROUND: Actinidia arguta leaves (AAL) are traditionally consumed as a vegetable and as tea in folk China and Korea. Previous studies have reported the anti-diabetic effect of AAL, but its bioactive components and mechanism of action are still unclear. AIM OF THE STUDY: This study aims to identify the hypoglycemic active components of AAL by combining serum pharmacochemistry and network pharmacology and to elucidate its possible mechanism of action. METHODS: Firstly, the effective components in mice serum samples were characterized by UPLC-Q/TOF-MSE. Furthermore, based on these active ingredients, network pharmacology analysis was performed to establish an "H-C-T-P-D" interaction network and reveal possible biological mechanisms. Finally, the affinity between serum AAL components and the main proteins in the important pathways above was investigated through molecular docking analysis. RESULTS: Serum pharmacochemistry analysis showed that 69 compounds in the serum samples were identified, including 23 prototypes and 46 metabolites. The metabolic reactions mainly included deglycosylation, dehydration, hydrogenation, methylation, acetylation, glucuronidation, and sulfation. Network pharmacology analysis showed that the key components quercetin, pinoresinol diglucoside, and 5-O-trans-p-coumaroyl quinic acid butyl ester mainly acted on the core targets PTGS2, HRAS, RELA, PRKCA, and BCL2 targets and through the PI3K-Akt signaling pathway, endocrine resistance, and MAPK signaling pathway to exert a hypoglycemic effect. Likewise, molecular docking results showed that the three potential active ingredients had good binding effects on the five key targets. CONCLUSION: This study provides a basis for elucidating the pharmacodynamic substance basis of AA against T2DM and further exploring the mechanism of action.

A comprehensive analysis of the chemical composition of Fraxinus mandshurica roots based on HPLC-DAD-MS, GC-MS and UPLC-ESI-Q-TOF-MS.

Fraxinus mandshurica is widely distributed around the world, which has significant economic value and pharmacological effects. However, its roots are often overlooked during processing and use. In this study, the preliminary identification of chemical components in F. mandshurica roots was carried out using ultra-performance liquid chromatography coupled with electrospray quadrupole time-of-flight mass spectrometry (UPLC-ESI-Q-TOF-MS), and a total of 37 characteristic components were identified, including 13 secoiridoids, 7 lignans, 6 coumarins, 4 flavonoids, 4 phenylethanols, 1 terpenoid and 2 other compounds. Meanwhile, to evaluate the 6 lignans content of F. mandshurica roots, the identification, quantitation analysis and methodological validation were performed by high-performance liquid chromatography with diode array detection mass spectrometry (HPLC-DAD-MS), which showed that the concentration range of standard compounds was 0.5-1000 µg/mL. The standard curve correlation coefficients (R2) were all greater than 0.9991, indicating that the linearity of the fitted curves was good. The highest lignan content in F. mandshurica roots was olivil (461.11 µg/g) and the lowest in buddlenol E (11.14 µg/g), and the total lignan content was 764.63 µg/g. The relative standard deviations (RSD, %) of both intra-day and inter-day precision were less than 1.95%. The RSD (%) of the reproducibility and stability experiments was less than 2.91%. The spiked recoveries of the samples were in the range of 98.29-102.62%, and the RSD (%) was in the range of 0.43-1.73, indicating that the method has high accuracy. In addition, a total of 20 volatile components in F. mandshurica roots were identified and quantified by gas chromatography-mass spectrometer (GC-MS) in this study, which laid a solid foundation for the comprehensive development and utilization of F. mandshurica resources.

Gut Microbiota Combined with Serum Metabolomics to Investigate the Hypoglycemic Effect of Actinidia arguta Leaves.

Actinidia arguta leaves (AAL) are an excellent source of bioactive components for the food industry and possess many functional properties. However, the hypoglycemic effect and mechanism of AAL remain unclear. The aim of this work was to investigate the potential hypoglycemic effect of AAL and explore its possible mechanism using 16S rRNA sequencing and serum metabolomics in diabetic mice induced by high-fat feeding in combination with streptozotocin injection. A total of 25 flavonoids from AAL were isolated and characterized, and the contents of the extract from the AAL ranged from 0.14 mg/g DW to 8.97 mg/g DW. The compound quercetin (2) had the highest content of 8.97 ± 0.09 mg/g DW, and the compound kaempferol-3-O-(2'-O-D-glucopyl)-ß-D-rutinoside (12) had the lowest content of 0.14 ± 0.01 mg/g DW. In vivo experimental studies showed that AAL reduced blood glucose and cholesterol levels, improved insulin sensitivity, and ameliorated oxidative stress and liver and kidney pathological damage. In addition, gut microbiota analysis found that AAL significantly reduced the F/B ratio, enriched the beneficial bacteria Bacteroides and Bifidobacterium, and inhibited the harmful bacteria Lactobacillus and Desulfovibrio, thereby playing an active role in intestinal imbalance. In addition, metabolomics analysis showed that AAL could improve amino acid metabolism and arachidonic acid metabolism, thereby exerting a hypoglycemic effect. This study confirmed that AAL can alleviate type 2 diabetes mellitus (T2DM) by regulating intestinal flora and interfering with related metabolic pathways, providing a scientific basis for its use as a dietary supplement and for further exploration of the mechanism of AAL against T2DM.