Molecular targets and mechanisms of Jiawei Jiaotai Pill on diabetic cardiomyopathy based on network pharmacology.

BACKGROUND: Jiawei Jiaotai Pill is commonly used in clinical practice to reduce apoptosis, increase insulin secretion, and improve blood glucose tolerance. However, its mechanism of action in the treatment of diabetic cardiomyopathy (DCM) remains unclear, hindering research efforts aimed at developing drugs specifically for the treatment of DCM. AIM: To explore the pharmacodynamic basis and molecular mechanism of Jiawei Jiaotai Pill in DCM treatment. METHODS: We explored various databases and software, including the Traditional Chinese Medicine Systems Pharmacology Database, Uniport, PubChem, GenCards, String, and Cytoscape, to identify the active components and targets of Jiawei Jiaotai Pill, and the disease targets in DCM. Protein-protein interaction network, gene ontology, and Kyoto Encyclopedia of Genes and Genomes analyses were used to determine the mechanism of action of Jiawei Jiaotai Pill in treating DCM. Molecular docking of key active components and core targets was verified using AutoDock software. RESULTS: Total 42 active ingredients and 142 potential targets of Jiawei Jiaotai Pill were identified. There were 100 common targets between the DCM and Jiawei Jiaotai Pills. Through this screening process, TNF, IL6, TP53, EGFR, INS, and other important targets were identified. These targets are mainly involved in the positive regulation of the mitogen-activated protein kinase (MAPK) MAPK cascade, response to xenobiotic stimuli, response to hypoxia, positive regulation of gene expression, positive regulation of cell proliferation, negative regulation of the apoptotic process, and other biological processes. It was mainly enriched in the AGE-RAGE signaling pathway in diabetic complications, DCM, PI3K-Akt, interleukin-17, and MAPK signaling pathways. Molecular docking results showed that Jiawei Jiaotai Pill's active ingredients had good docking activity with DCM's core target. CONCLUSION: The active components of Jiawei Jiaotai Pill may play a role in the treatment of DCM by reducing oxidative stress, cardiomyocyte apoptosis and fibrosis, and maintaining metabolic homeostasis.

Comparison of therapeutic effects of different acupuncture and moxibustion therapies in the treatment of peripheral facial nerve paralysis: A protocol for systematic review and network meta-analysis.

BACKGROUND: Previous evidences show that acupuncture and moxibustion therapy has positive effects on peripheral facial nerve paralysis (PFP), but there are many acupuncture treatments based on meridian theory, and there are differences in the efficacy of each program. This study will compare the clinical efficacy of different acupuncture treatments for PFP through mesh meta-analysis. METHODS: Randomized controlled trials of acupuncture therapy in the treatment of PFP are going to be retrieved from 8 Science databases including CNKI, Wanfang, VIP and Chinese Biomedical Science, PubMed, Embase, Web of Science and the Cochrane Library from establishment to January 2022. We will use the Cochrane Risk Bias Assessment Tool to assess the quality of the studies and the grading of recommendation assessment, development and evaluation method to assess the strength of the evidence. All data analyses will be performed by Revman5.3, Gemtc 0.14.3, and Stata 14.0. RESULTS: This study will evaluate the efficacy of different acupuncture treatments for PFP by evaluating clinical efficacy rate, facial nerve function score, facial disability score scale, facial electromyography, adverse reactions, etc, and further explore the mechanism of action of each therapy. CONCLUSION: This study will provide a reliable evidence-based basis for selecting the best acupuncture treatment for PFP. TRIAL REGISTRATION: Open science framework registration number: DOI 10.17605/OSF.IO/XQRK9.

Anti-inflammatory effects of curcumin in acute lung injury: In vivo and in vitro experimental model studies.

Inflammation plays a major role in the pathogenesis of acute lung injury (ALI), but the mechanism remains unclear. Current anti-inflammatory therapy has poor efficacy on ALI. The aim of this study was to investigate the protective mechanism of curcumin against ALI. In in vivo experiments, curcumin significantly alleviated lung inflammation, histopathological injury and MPO activity, serum concentrations of CCL7, IL-6 and TNF-α, and mortality in mice compared to the model group. RAW264.7 cells cultured in the presence of lipopolysaccharide and adenosine triphosphate showed significantly lower viability, higher pyroptotic percentage and inflammation, but supplement of curcumin increased the cell viability, reduced pyroptosis and inflammation. Additionally, the expressions of NF-κB and pyroptosis related proteins were notably increased, while Sirtuin 1 (SIRT1) was decreased in both in vivo and in vitro ALI models. The results suggested that curcumin remarkably inhibited the expression of NF-κB and pyroptosis related proteins and increased the expression of SIRT1. However, EX527, a SIRT1 inhibitor, blocked the protective effect of curcumin against ALI. In conclusion, curcumin has protective effect against ALI. It may inhibit inflammatory process by inhibiting the activation of NLRP3 inflammasome-dependent pyroptosis through the up-regulation of SIRT1.

The different effects of concept definition and interactive imagery encoding on associative recognition for word and picture stimuli.

Traditional view holds that associative recognition require recollection while familiarity can't support associative recognition. However, recent research indicate that familiarity can also contribute to associative recognition when the stimuli are unitized in encoding. Here, we investigated the electrophysiological correlates of retrieval of word and picture stimuli in three encoding conditions. Semantically unrelated word pairs or picture pairs were encoded in concept definition, interactive imagery, and item comparison conditions, separately. In test, the participants were required to discriminate between old pairs that appeared in the same pairing as in study, rearranged pairs that appeared in different pairings in study, or completely new pairs. The behavioral results revealed that higher associative recognition was observed in interactive imagery condition than in concept definition condition, with item comparison condition eliciting the worst recognition, regardless of word or picture stimuli. ERP results of word stimuli revealed that the FN400 old/new effect was solely elicited in concept definition and interactive imagery conditions, but not in item comparison condition. However, ERP results of picture stimuli revealed that the late FN400 old/new effect was observed in three encoding conditions and that larger magnitude of old/new effect was elicited in item comparison condition than in interactive imagery condition. There may be different neural mechanisms of unitization on associative recognition for word and picture stimuli. These findings suggested that the pattern of engagement of familiarity during successful retrieval was dependent on the stimulating properties and the encoding conditions. We will discuss the possibility that top-down unitization which manipulates two unrelated stimuli through instructions may lead to the engagement of specific forms of familiarity-association familiarity and item familiarity.

[Effect of warm acupuncture at Yifeng (TE 17) on facial paralysis with periauricular pain during pregnancy].

OBJECTIVE: To compare the curative effect between the warm acupuncture at Yifeng (TE 17) combined with conventional acupuncture and TDP plus conventional acupuncture on facial paralysis with periauricular pain during pregnancy. METHODS: A total of 68 patients were randomized into an observation group (36 cases, 3 cases dropped off) and a control group (32 cases, 1 case dropped off). First week, TDP light was used on the affected side in the control group, and warm acupuncture at Yinfeng (TE 17) on the affected side was used in the observation group, both once a day. From the second week, both groups were given acupuncture at Chengjiang (CV 24) and the affected side of Cuanzhu (BL 2), Yangbai (GB 14), Taiyang (EX-HN 5), Yingxiang (LI 20), Dicang (ST 4), etc. and electroacupuncture (continuous wave, 2 Hz in frequency) was connected at Cuanzhu (BL 2) and Taiyang (EX-HN 5), Jiache (ST 6) and Dicang (ST 4). Both treatments were given every other day for 4 weeks totally. The visual analogue scale (VAS) score of the periauricular pain degree before treatment and after 1 week of treatment, the House-Brackmann (H-B) facial nerve function grading scale and facial disability index (FDI) score before treatment and after 2, 4 weeks of treatment were compared between the two groups. RESULTS: After 1 week of treatment, the VAS scores of both groups decreased (P<0.001), and the variation in the observation group was larger than the control group (P<0.01). After 2 and 4 weeks of treatment, the H-B grading of both groups were improved (P<0.01, P<0.05), and those in the observation group were better than the control group (P<0.05). After 2 and 4 weeks of treatment, the FDI physical function (FDIP) scores of both groups were higher (P<0.01), and the FDI social life function (FDIS) scores were lower than before treatment (P<0.05, P<0.01), and the FDIP scores in the observation group were higher than those in the control group (P<0.05). CONCLUSION: Warm acupuncture at Yinfeng (TE 17) combined with conventional acupuncture can effectively improve the periauricular pain and facial nerve function in patients of facial paralysis with periauricular pain during pregnancy, and the curative effect is better than TDP plus conventional acupuncture.

[Clinical observation on time-effect of electroacupuncture for idiopathic facial paralysis].

OBJECTIVE: To observe the effect of different acupuncture frequency and duration of needle retention on idiopathic facial paralysis, and optimize the acupuncture treatment plan. METHODS: A total of 140 patients were randomized into a group A (37 cases, 3 cases dropped off), a group B (35 cases, 3 cases dropped off), a group C (34 cases, 1 case dropped off) and a group D (34 cases, 1 case dropped off). Under the same basic treatment, acupuncture intervention time (day 8 of morbidity), acupoint selection [Cuanzhu (BL 2), Yangbai (GB 14), Taiyang (EX-HN 5), Yingxiang (LI 20), Jiache (ST 6), Dicang (ST 4) on the affected side, Chengjiang (CV 24) and Hegu (LI 4) on the unaffected side] and electroacupuncture intervention, different acupuncture interval time and duration of needle retention were applied. In the group A, the treatment was given 20 min once a day, while the group B 30 min once a day, the group C 20 min once every 2 days, the group D 30 min once every 2 days. Totally 20-day treatment were required. The House-Brackmann (H-B) facial nerve function grading system was used to evaluate the improvement of clinical symptom, the situation and latency periods of the R1 wave in blink reflex and facial nerve motor conduction before and after treatment were observed in the 4 groups. RESULTS: After treatment, the cured rates in the 4 groups were 44.1% (15/34), 46.9% (15/32), 57.6% (19/33) and 51.5% (17/33), there was no significant difference among 4 groups (P>0.05). The situation and latency periods of the R1 wave in blink reflex and latency periods and amplitude of facial nerve motor conduction after treatment were improved in the 4 groups (P<0.01, P<0.05), there was no significant difference among 4 groups (P>0.05). CONCLUSION: Acupuncture 20 min once a day, 30 min once a day, 20 min once every 2 days and 30 min once every 2 days have significant effect on the recovery of idiopathic facial paralysis, and the effect is comparable.

Melatonin suppresses milk fat synthesis by inhibiting the mTOR signaling pathway via the MT1 receptor in bovine mammary epithelial cells.

Milk fat content is an important criterion for assessing milk quality and is one of the main target traits of dairy cattle breeding. Recent studies have shown the importance of melatonin in regulating lipid metabolism, but the potential effects of melatonin on milk fat synthesis in bovine mammary epithelial cells (BMECs) remain unclear. Here, we showed that melatonin supplementation at 10 µmol/L significantly downregulated the mRNA expression of lipid metabolism-related genes and resulted in lower lipid droplet formation and triglyceride accumulation. Moreover, melatonin significantly upregulated melatonin receptor subtype melatonin receptor 1a (MT1) gene expression, and the negative effects of melatonin on milk fat synthesis were reversed by treatment with the nonselective MT1/melatonin receptor subtype melatonin receptor 1b (MT2) antagonist. However, a selective MT2 antagonist did not modify the negative effects of melatonin on milk fat synthesis. In addition, KEGG analysis revealed that melatonin inhibition of milk fat synthesis may occur via the mTOR signaling pathway. Further analysis revealed that melatonin significantly suppressed the activation of the mTOR pathway by restricting the phosphorylation of mTOR, 4E-BP1, and p70S6K, and the inhibition of melatonin on milk fat synthesis was reversed by mTOR activator MHY1485 in BMECs. Furthermore, in vivo experiments in Holstein dairy cows showed that exogenous melatonin significantly decreased milk fat concentration. Our data from in vitro and in vivo studies revealed that melatonin suppresses milk fat synthesis by inhibiting the mTOR signaling pathway via the MT1 receptor in BMECs. These findings lay a foundation to identify a new potential means for melatonin to modulate the fat content of raw milk in Holstein dairy cows.

A study on screening and antitumor effect of CD55-specific ligand peptide in cervical cancer cells.

BACKGROUND: To improve the targeting ability of antitumor drugs, we identified the antigens with high expression on the surface of tumor cells associated with tumor escape, such as the complement regulatory protein CD55 molecule, which is also known as the decay accelerating factor. In this study, phage display technology was used to screen and identify CD55-specific ligand peptide (CD55sp) bound to CD55 molecule on the surface of cervical cancer HeLa cells. We then explored the role of this peptide in inhibiting the growth of cervical cancer cells in vitro. Our characterization of CD55sp will provide implication for tumor target therapy. METHODS: The phage bound to the surface of HeLa cells were isolated by phage display technology. Positive phage clones were identified by ELISA. Phage was then amplified and determined by agarose gel electrophoresis after monoclonal DNA extraction. DNA sequencing and bioinformatical analysis were conducted to obtain specific ligand peptides. Flow cytometry and immunofluorescence were used to measure the expression of CD55 molecule on the surface of tumor and normal cells. Subsequently, the effects of CD55sp on the proliferation and apoptosis of HeLa and SiHa cells were determined by Cell Counting Kit-8 (CCK-8), flow cytometry, and TUNEL assay, respectively. The morphology of apoptotic cells was examined by electron microscope. The distribution of Cleaved caspase-3 was detected by immunofluorescence. The expression of bcl-2 and Cleaved caspase-3 were determined by Western blot. RESULTS: The results showed that the peptide (QVNGLGERSQQM) can bind to the CD55 molecule on the surface of cervical cancer HeLa and SiHa cells as a ligand peptide. It can also effectively inhibit the proliferation of cervical cancer cells and induce cell apoptosis. CONCLUSION: This study demonstrates that CD55sp screened by phage display technology plays a strong antitumor role.

Mechanisms of Heshouwuyin in regulating apoptosis of testicular cells in aging rats through mitochondrial pathway.

BACKGROUND: Polygonum multiflorum has important effects on anti-aging and immunity enhancement. Many traditional Chinese medicine preparations based on Polygonum multiflorum are widely used for the clinical prevention and treatment of aging. However the mechanisms of these herb mixtures are often unknown. This study investigates the effect of Heshouwuyin, a Chinese herbal compound for invigorating the kidney, on the regulation of testicular cells apoptosis in aging rats. METHODS: In this study, 18-month-old Wistar rats served as a model of natural aging and 12-month-old rats served as a young control group. Heshouwuyin group 1 and group 2 were comprised 18-month-old rats given Heshouwuyin intragastrically for 60 days and 30 days respectively. Then testes of the young control group were isolated in the age of 12 months, the other three groups were in the age of 18 months. RESULTS: TUNEL assay showed that the rate of testicular cell apoptosis was obviously higher and Flow cytometry analysis showed that the rate of cell proliferation was significantly lower in the natural aging group than in the young control group and that intervention with Heshouwuyin could reverse this phenomenon. Therefore, we further applied microarray analysis to screen out differentially expressed genes regulated by Heshouwuyin and related to cell apoptosis. The expression of these genes was observed by quantitative fluorescence PCR, immunofluorescence staining, and western blot. The results showed that the expression of 14-3-3σ was significantly lower and that the expression of DR6, BAX, caspase-3 and Cytc were significantly higher in the natural aging group than in the young control group, but intervention with Heshouwuyin significantly reversed this phenomenon. Moreover, the curative efficacy of Heshouwuyin after 60 days was better than that of Heshouwuyin after 30 days. CONCLUSION: Our study suggests that Heshouwuyin has anti-aging effects on the testis by means of inhibiting the occurrence of apoptosis in spermatogenic cells, thus improving the spermatogenic function of the testis. This is mainly achieved by regulating the expression of key genes in the mitochondrial apoptosis pathway.