Quantitative proteomics analysis based on data-independent acquisition reveals the effect of Shenling Baizhu powder (SLP) on protein expression in MAFLD rat liver tissue.

BACKGROUND: Metabolic associated fatty liver disease (MAFLD) has become the most common chronic liver disease worldwide, and it is also a high-risk factor for the development of other metabolic diseases. Shenling Baizhu powder (SLP) is a traditional Chinese herbal formula with good clinical efficacy against MAFLD. However, its molecular mechanism for the treatment of MAFLD is still not fully understood. This study used quantitative proteomics analysis to reveal the SLP action mechanism in the treatment of MAFLD by discovering the effect of SLP on protein expression in the liver tissue of MAFLD rats. MATERIALS AND METHODS: Q-Orbitrap LC-MS/MS was used to identify the incoming blood compounds of SLP. The 18 SD male rats were randomly divided into 3 groups (n = 6): control group, HFD group and SLP group. The HFD group and SLP group were established as MAFLD rat models by feeding them a high-fat diet for 4 weeks. Afterwards, the SLP group was treated with SLP (10.89 g/kg/d) for 3 weeks. Biochemical parameters and liver pathological status were measured. Rat liver tissue was analyzed using DIA-based quantitative proteomics and the DEPs were validated by western blotting analysis. RESULTS: A total of 18 active compounds of SLP were identified and isolated to enter the bloodstream. Comparison of DEPs between control group vs. HFD group and HFD group vs. SLP group revealed that SLP restored the expression of 113 DEPs. SLP catalyzes oxidoreductase activity and binding activity on mitochondria and endoplasmic reticulum to promote lipid oxidative catabolism, maintain oxoacid metabolic homeostasis in vivo and mitigate oxidative stress-induced hepatocyte injury. And 52 signaling pathways including PPAR signaling, arachidonic acid metabolism and glycine, serine and threonine metabolism were enriched by KEGG. PPI topology analysis showed that Cyp4a2, Agxt2, Fabp1, Pck1, Acsm3, Aldh1a1, Got1 and Hmgcs2 were the core DEPs. The western blotting analysis verified that SLP was able to reverse the increase in Fabp1 and Hmgcs2 and the decrease in Pck1 induced by HFD, and the results were consistent proteomic data. CONCLUSION: SLP ameliorates hepatic steatosis to exert therapeutic effects on MAFLD by inhibiting the expression of lipid synthesis genes and inhibiting lipid peroxidation in mitochondria. This study provides a new idea and basis for the study of SLP in the treatment of MAFLD and provides an experimental basis for the clinical application of SLP.

NK cells mediate the cumulative analgesic effect of electroacupuncture in a rat model of neuropathic pain.

BACKGROUND: Cumulating evidence has revealed the effectiveness of acupuncture therapy in relieving pain via immunoregulation. However, its underlying mechanism remains unknown. The present study was designed to determine the changes of immunogenic responses at different time-points of electroacupuncture (EA) interventions in neuropathic pain rats. METHODS: The neuropathic pain model was established by ligature of the left sciatic nerve to induce chronic constriction injury (CCI). EA was applied at Zusanli (ST36) and Yanglingquan (GB34) for the EA groups. The thermal pain threshold was detected with an algesia-detector. The subgroups of plasma and splenic lymphocytes were determined via fluorescence-activated cell sorting. Specific inflammatory cytokines were assayed using an ELISA-based bead multiplex assay. The activities of splenic natural killer (NK) cells and cytotoxic T lymphocytes were detected by methyl thiazolyl tetrazolium colorimetric method. For confirming the involvement of NK cell in EA-analgesia, anti-asialo-ganglio-N-tetraosylceramide (anti-asialo-GM1) antibody was given to CCI rats before EA. RESULTS: Following CCI, the thermal pain threshold of the affected hind footpad was significantly decreased, and increased from the 3rd day to the 12th day after EA interventions, presenting a time-dependent tendency from the 5th day on. From day 3 to 5 of EA interventions, the percentages and activity of splenic NK cells, concentrations of splenic interleukin-2 (IL-2) and beta-endorphin (ß-EP) were significantly increased. Meanwhile, the concentrations of plasma IL-2, IL-1ß and gamma-interferon (IFN-γ) were significantly decreased and returned to the normal level on day 12 following EA. Plasma transforming growth factor-ß (TGF-ß) levels were considerably upregulated on day 5 and 12 following EA. The CD4+/CD8+ T cell ratio was markedly downregulated compared with the control and CCI groups on day 5 and returned to the normal level on day 12 following EA. After depleting NK cells by anti-asialo-GM1 antibody, the increased thermal pain threshold following EA intervention was obviously reduced. CONCLUSIONS: Repeated EA interventions have a time-dependent cumulative analgesic effect in neuropathic pain rats, which is closely associated with its regulatory effects on NK cells, splenic IL-2, ß-EP, and plasma IL-2, IL-1ß, IFN-γ and TGF-ß levels.

Ligand-free Pd-catalyzed highly selective arylation of activated and unactivated alkenes via oxidative and reductive heck coupling.

In this work, an eco-friendly, green, efficient approach for oxidative and reductive Heck-Mizoroki (HM) reactions was developed, which offered acceptable yields from first-pass experiments. Mono-arylation was achieved without the use of ligands, directing groups, or prefunctionalized alkenes. Considering mild reaction conditions, good functional group compatibility, and great regioselectivity, the method can find broad applications in novel medicine and material development and discovery processes.

Proteomic analysis of differential proteins related to anti-nociceptive effect of electroacupuncture in the hypothalamus following neuropathic pain in rats.

Increasing evidence has been accumulated for the effectiveness of acupuncture therapy in relieving pain. However, there are limited data on regulation of protein expression after electroacupuncture (EA) intervention. Thus, the present study is designed to determine changes in protein expression following EA stimulation in rats with sciatic nerve chronic constrictive injury (CCI) induced neuropathic pain. Sixty Wistar rats were equally randomized into normal control group, CCI group, and CCI with EA stimulation (EA) group. The CCI model was established by ligature of the left sciatic nerve. EA stimulation was applied at Zusanli (ST36) and Yanglingquan (GB34) in the EA group. Differentially expressed hypothalamic proteins in the three groups were identified by 2-D gel electrophoresis and matrix-assisted laser desorption/ionization time of flight mass spectrometry. The functional clustering and pathway of the identified proteins were analyzed by Mascot software. Results showed that, after CCI, the thermal pain threshold of the affected hind footpad was decreased and was reversed gradually by 12 sessions of EA treatment. Following EA intervention, there were 17 hypothalamic proteins identified with significant changes in the expression (>twofold). Three gene-ontologies (oxidoreductase activity, oxidation reduction, and protein binding) were enriched, while there was a significant regulation of glycolysis/gluconeogenesis/hexose metabolism pathway. These data demonstrate that EA intervention can attenuate pain via regulation of expression of multiple proteins in the hypothalamus. Further, hypothalamic glucose metabolism may be important in supporting energy and neurotransmitter homeostasis in the effects of EA intervention.

Artificial intelligence for healthcare and medical education: a systematic review.

BACKGROUND: Human society has entered the age of artificial intelligence, medical practice and medical education are undergoing profound changes. Artificial intelligence (AI) is now applied in many industries, particularly in healthcare and medical education, where it deeply intersects. The purpose of this paper is to overview the current situation and problems of "AI+medicine/medical" education and to provide our own perspective on the current predicament. METHODS: We searched PubMed, Embase, Cochrane and CNKI databases to assess the literature on AI+medical/medical education from 2017 to July 2022. The main inclusion criteria include literature describing the current situation or predicament of "AI+medical/medical education". RESULTS: Studies have shown that the current application of AI in medical education is focused on clinical specialty training and continuing education, with the main application areas being radiology, diagnostics, surgery, cardiology, and dentistry. The main role is to assist physicians to improve their efficiency and accuracy. In addition, the field of combining AI with medicine/medical education is steadily expanding, and the most urgent need is for policy makers, experts in the medical field, AI and education, and experts in other fields to come together to reach consensus on ethical issues and develop regulatory standards. Our study also found that most medical students are positive about adding AI-related courses to the existing medical curriculum. Finally, the quality of research on "AI+medical/medical education" is poor. CONCLUSION: In the context of the COVID-19 pandemic, our study provides an innovative systematic review of the latest "AI+medicine/medical curriculum". Since the AI+medicine curriculum is not yet regulated, we have made some suggestions.

Differential proteomics analysis of the analgesic effect of electroacupuncture intervention in the hippocampus following neuropathic pain in rats.

BACKGROUND: Evidence is building steadily on the effectiveness of acupuncture therapy in pain relief and repeated acupuncture-induced pain relief is accompanied by improvement of hippocampal neural synaptic plasticity. To further test the cellular and molecular changes underlying analgesic effect of acupuncture, the global change of acupuncture associated protein profiles in the hippocampus under neuropathic pain condition was profiled. METHODS: The chronic constrictive injury (CCI) model was established by ligature of the unilateral sciatic nerve in adult Wistar rats. Rats were randomized into normal control (NC) group, CCI group, and CCI with electroacupuncture (EA) stimulation group. EA was applied to bilateral Zusanli (ST36) and Yanglingquan (GB34) in the EA group. Differentially expressed proteins in the hippocampus in the three groups were identified by two-dimensional gel electrophoresis and matrix-assisted laser desorption/ionization time of flight mass spectrometry. The functional clustering of the identified proteins was analyzed by Mascot software. RESULTS: After CCI, the thermal pain threshold of the affected hind footpad was decreased and was reversed gradually by 12 sessions of acupuncture treatment. Following EA, there were 19 hippocampal proteins identified with significant changes in expression (>2-fold), which are involved in metabolic, physiological, and cellular processes. The top three canonical pathways identified were "cysteine metabolism", "valine, leucine, and isoleucine degradation" and "mitogen-activated protein kinase (MAPK) signaling". CONCLUSIONS: These data suggest that the analgesic effect of EA is mediated by regulation of hippocampal proteins related to amino acid metabolism and activation of the MAPK signaling pathway.

Postconditioning reduces infarct size and cardiac myocyte apoptosis via the opioid receptor and JAK-STAT signaling pathway.

Brief intermittent episodes of ischemia and reperfusion could reduce infarct size, a phenomenon called "postconditioning" at the onset of reperfusion after a prolonged period of ischemia. To investigate whether the opioid receptors and signaling factor JAK-STAT might be responsible for the cardioprotection in ischemic postconditioning, and the possible molecular machinery of cardioprotection. Hundred and twenty healthy New Zealand rabbits were divided into six groups. The myocardial infarct size, cardiac myocyte apoptosis, BCL-2 and P-Stat3 protein expression were tested in the current study. The results suggested that ischemic postconditioning might increase BCL-2 protein expression by activating the opioid receptors and JAK-STAT signaling pathway, and also to reduce ischemia-reperfusion-induced cardiomyocyte apoptosis and to play a key role in myocardial protection. However, further research still needs to be done to unravel the underlying mechanisms.

A multiaxial molecular ferroelectric with record high TC designed by intermolecular interaction modulation.

Through precise and ingenious molecular modification, we successfully obtained a multiaxial ferroelectric, [FEtDabco]ZnI3 (N-fluoroethyl-N'-ZnI3-1,4-diazabicyclo[2.2.2]octonium), with a record high Tc (540 K) among molecular ferroelectrics, which is promising for application under extreme thermal conditions.

Combined metal/air fuel cell and electrocoagulation process: Energy generation, flocs production and pollutant removal.

Electrocoagulation (EC) which is characterized by in-situ generation of highly absorbable hydroxide flocs, is an environmentally friendly process for treating heavy metal ions and toxic organic wastewater. In order to decrease EC's energy consumption, a combined metal/air FC-EC process which contains two successive parts: metal/air fuel cell (FC) and electrocoagulation (EC) was studied with the consideration of hydroxide flocs production, pollutant removal and energy generation analysis. For the combined iron/air FC-EC process, the porous nickel cathode which has a good performance in high polarization zone was selected as the ideal air cathode. It was found that iron/air FC-EC with acid electrolyte condition has a high energy generation (as high as 20% EC energy consumption). The energy generation increases with iron/air FC time. Also energy generation increases with wastewater's conductivity. Beside the energy generation, the iron/air fuel cell generate extra coagulants Fe2+ for the subsequent EC process. The coagulants generated from iron/air FC and EC process together have further spontaneous hydrolysis reactions with the OH- to form hydroxide flocs, which are beneficial for a rapid adsorption and pollutant trapping. Compared with EC process, iron/air (or Al/air) FC-EC process shows lower energy consumption and high removal efficiency for treating acid wastewater.

[Effects of puerarin on ADRP gene expression in fatty tissue of type 2 diabetes mellitus rats].

OBJECTIVE: To observe the effects of puerarin on ADRP gene mRNA expression in fatty tissue of type 2 diabetes mellitus rats (T2DM). METHOD: Wiastar rats of T2DM model were made by feeding with high glucose and fat diet and injecting with small dose of streptozocin (25 mg x kg(-1)). 40 model rats were randomly divided into model control group and three puerarin groups (40, 80, 160 mg x kg(-1)), another 10 rats were selected as normal control group. FBG and FINS were measured to calculate IR after rats were injected consecutively for 6 weeks. The level of ADRP gene mRNA in fatty tissue was determined by RT-PCR after rats were injected eight weeks. RESULT: Compared with model control group, high and middle dosage of puerarin can decreased ADRP gene mRNA expression in fatty tissue obviously, FBG, IR level in each puerarin group and FINS in high and middle dosage puerarin groups decreased obviously. CONCLUSION: Puerarin can decrease the blood glucose level of T2DM by downregulating ADRP mRNA expression and depressing the insulin resistance.

Correlation between the cumulative analgesic effect of electroacupuncture intervention and synaptic plasticity of hypothalamic paraventricular nucleus neurons in rats with sciatica.

In the present study, a rat model of chronic neuropathic pain was established by ligation of the sciatic nerve and a model of learning and memory impairment was established by ovariectomy to investigate the analgesic effect of repeated electroacupuncture stimulation at bilateral Zusanli (ST36) and Yanglingquan (GB34). In addition, associated synaptic changes in neurons in the paraventricular nucleus of the hypothalamus were examined. Results indicate that the thermal pain threshold (paw withdrawal latency) was significantly increased in rats subjected to 2-week electroacupuncture intervention compared with 2-day electroacupuncture, but the analgesic effect was weakened remarkably in ovariectomized rats with chronic constrictive injury. 2-week electroacupuncture intervention substantially reversed the chronic constrictive injury-induced increase in the synaptic cleft width and thinning of the postsynaptic density. These findings indicate that repeated electroacupuncture at bilateral Zusanli and Yanglingquan has a cumulative analgesic effect and can effectively relieve chronic neuropathic pain by remodeling the synaptic structure of the hypothalamic paraventricular nucleus.

The cumulative analgesic effect of repeated electroacupuncture involves synaptic remodeling in the hippocampal CA3 region.

In the present study, we examined the analgesic effect of repeated electroacupuncture at bilateral Zusanli (ST36) and Yanglingquan (GB34) once a day for 14 consecutive days in a rat model of chronic sciatic nerve constriction injury-induced neuropathic pain. In addition, concomitant changes in calcium/calmodulin-dependent protein kinase II expression and synaptic ultrastructure of neurons in the hippocampal CA3 region were examined. The thermal pain threshold (paw withdrawal latency) was increased significantly in both groups at 2 weeks after electroacupuncture intervention compared with 2 days of electroacupuncture. In ovariectomized rats with chronic constriction injury, the analgesic effect was significantly reduced. Electroacupuncture for 2 weeks significantly diminished the injury-induced increase in synaptic cleft width and thinning of the postsynaptic density, and it significantly suppressed the down-regulation of intracellular calcium/calmodulin-dependent protein kinase II expression in the hippocampal CA3 region. Repeated electroacupuncture intervention had a cumulative analgesic effect on injury-induced neuropathic pain reactions, and it led to synaptic remodeling of hippocampal neurons and upregulated calcium/calmodulin-dependent protein kinase II expression in the hippocampal CA3 region.

[Effects of electroacupuncture of "Futu" (LI 18), etc. on pain behavior and expression of GABA receptor subunit genes in cervical spinal cord in rats with thyroid regional pain].

OBJECTIVE: To observe the effect of electroacupuncture (EA) at different acupoints on the expression of gamma aminobutyric (GABA) receptor (R) subunit genes in the cervical spinal cord in rats with thyroid regional inflammatory pain so as to analyze its analgesic mechanism for thyroid surgery. METHODS: A total of 50 Wistar rats were randomized into control, model, Futu (LI 18), Hegu (LI 4)-Neiguan (PC 6, LI 4-PC 6), Zusanli (ST 36)-Yanglingquan (GB 34, ST 36-GB 34) groups, with 10 rats in each group. Thyroid regional pain model was established by subcutaneous injection of 2.5% formalin (100 microL). Ten minutes after modeling, EA (2 Hz/15 Hz, 1 mA) was applied to LI 18, LI 4-PC 6 and ST 36-GB 34 for 30 min, respectively. The animals' face-grooming (FG) times in 5 min and thermal pain threshold (paw withdrawal latency, PWL) were recorded. The expression of GABA(A) R, GABA(B) R1, and GABA(B) R2 genes in the cervical 1-3 segments of the spinal cord 80 min after modeling was detected by using reversed transcription-polymerase chain reaction (RT-PCR). Histological changes of the tissues of the thyroid region were observed by using H. E. staining. RESULTS: After subcutaneous injection of formalin, the animals' FG times in 5 min were increased considerably and the thermal pain threshold was decreased obviously in the model group (P < 0.05). Concomitantly, the expression levels of GABA(B) R1, and GABA(B) R2 genes of the cervical spinal cord were upregulated significantly in the model group (P < 0.05), and GABA(A) R expression was increased slightly (P > 0.05). Compared with the model group, the FG times in 5 min in the LI 18 and LI 4-PC 6 groups at 40 min and 70 min after modeling were decreased significantly (P < 0.05), and their thermal pain threshold values were increased markedly (P < 0.05). The expression levels of GABA(B) R1 mRNA, GABA(B) R2 mRNA and GABAA R mRNA were significantly higher in the LI 18 and LI 4-PC 6 groups than in the model group (P < 0.05). The expression level of GABA(B) R1 mRNA of the ST 36-GB 34 group was obviously higher than that of the model group (P < 0.05). The inflammatory cells in the formalin-injected thyroid region were relatively fewer in the LI 18 and LI 4-PC 6 groups than in the model group. CONCLUSION: Both EA of LI 18 and LI 4-PC 6 can significantly suppress formalin-injection induced pain reactions in the thyroid region, which may be closely associated with its effects in upregulating expression levels of cervico-spinal GABA(B) R1 mRNA, GABA(B) R2 mRNA and GABA(A) R mRNA, and reduce regional inflammatory reactions in the thyroid region.

[Effects of electroacupuncture at different acupoints on the pain behavior and NMDA receptor 2 B subunit mRNA and protein expression and phosphorylation level in the cervical spinal cord in rats with thyroid regional pain].

OBJECTIVE: To observe the effect of electroacupuncture (EA) of different acupoint groups on the expression of NR 2 B subunit of N-methyl-D-aspartate (NMDA) receptor in the cervical spinal cord in rats with thyroid regional pain so as to analyze the analgesic mechanism of acupuncture for performing thyroid surgery. METHODS: A total of 50 Wistar rats were randomized into control, model, EA-Futu (ST 32), EA-Hegu (LI 4)-Neiguan (PC 6, EA-LI 4-PC 6), EA-Zusanli (ST 36)-Yanglingquan (GB 34, EA-ST 36-GB 34) groups, with 10 cases in each. Thyroid regional pain model was established by subcutaneous injection of 2.5% formaldehyde. Ten minutes after modeling, EA (2 Hz/100 Hz, 1 mA) was applied to ST 32, LI 4-PC 6 and ST 36-GB 34 for 30 min respectively. The animals' face-grooming (FG) times and paw withdrawal latency (PWL) of radiant heat irradiation were recorded. The spinal cord tissues of the cervical 1-3 segments were removed for detecting the expression of NR 2 B mRNA and protein of NMDA receptor with reversed transcription-polymerase chain reaction and Western blotting techniques separately. RESULTS: After subcutaneous injection of 2.5% formaldehyde, the animals' FG times increased considerably and the PWL was shortened obviously (P<0.05). Compared with model group, the FG times of EA-ST 32 and EA-LI 4-PC 6 groups at 40-45 min and 70-75 min after modeling decreased significantly, and their PWL prolonged markedly (P<0.05). The effect of EA-ST 32 was apparently superior to that of EA-LI 4-PC 6 group in reducing FG times. No significant differences were found between EA-ST 32 and EA-LI 4-PC 6 groups in PWL, and between model and EA-ST 36-GB 34 groups (P>0.05). Results of NR 2 B mRNA and protein detections showed no significant differences among the 5 groups in their expression (P>0.05). Comparison of the phosphorylated NR 2 B among 5 groups showed that EA-ST 32 and EA-LI 4-PC 6 could effectively down-regulate 2.5% formaldehyde induced increase of NR 2 B phosphorylation levels (P<0.05), while EA-ST 36-GB 34 had no obvious effect on it (P>0.05). CONCLUSION: Both EA-ST 32 and EA-LI 4-PC 6 can significantly suppress thyroid regional pain induced behavior reactions, which may be closely associated with their effects in down-regulating NR 2 B phosphorylated level. The analgesic effect of EA-ST 32 and EA-LI 4-PC 6 for thyroid surgery is relatively more effective in comparison with EA-ST 36-GB 34.

[Effects of electroacupuncture of different acupoints groups on blood pressure and heart rate variability in rats].

OBJECTIVE: To observe the effect of electroacupuncture (EA) of different acupoint groups on mean arterial pressure (MAP) and heart rate variability (HRV) in hypotension rats. METHODS: A total of 70 Wistar female rats were randomized into model, "Neiguan" (PC 6)-"Daling" (PC 7), "Waiguan" (SJ 4)-"Yangchi" (SJ 5), "Tianshu" (ST 25)-"Wailing" (ST 26), "Dachangshu" (BL 25)-"Qihaishu" (BL 24), "Baihui" (GV 20)-"Qianshencong" (EX-HN), and"Guangming" (GB 37)-"Xuanzhong" (GB 39) groups, with 10 cases in each. Hypotension model was established by bleeding (2.5-3 ml) through carotid artery. Immediately after bleeding, EA (2/15 Hz, 1 mA, 30 min) was applied to the above-mentioned acupoints of the 6 EA groups. MAP and ECG were recorded, then HRV was analyzed by using software Chart 5.2.1. RESULTS: MAP declined significantly after bleeding. Compared with model group, MAP values of PC6-PC7 and GB37-GB39 groups increased significantly 15 min and 30 min after bleeding, and those of ST25-ST26 and GV20-EX-HN groups also increased apparently 30 min after bleeding (P<0.05). No marked effects were observed in EA of SJ4-SJ5 and BL25-BL24 groups (P>0.05). The effect of PC6-PC7 and GB37-GB39 groups was significantly superior to that of SJ4-SJ5, BL25-BL24 and GV20-EX-HN groups in elevating MAP 30 min after bleeding (P<0.05). Compared with model group, heart rate (HR) of PC6-PC7 group was increased significantly 15 min and 30 min after bleeding (P<0.05). After bleeding, low frequency (LF), LF/high frequency (HF) and very low frequency (VLF) increased apparently. Compared with model group, LF, LF/HF and VLF of PC6-PC7 and GB37-GB39 groups decreased significantly 30 min after bleeding (P<0.05), suggesting a better balancing effect of EA of PC6-PC7 and GB37-GB39 on the activities of sympathetic and vagus nerves. CONCLUSION: EA of different acupoint groups has its own relative specificity in regulating MAP and HR in the rat, and PC6-PC7 EA and GB37-GB39 EA have a better efficacy, which is closely associated with their effects in balancing activities of the autonomic nerve system.