Cardioprotective Effects of Exercise: The Role of Irisin and Exosome.

Exercise is an effective measure for preventing and treating cardiovascular diseases, although the exact molecular mechanism remains unknown. Previous studies have shown that both irisin and exosomes can improve the course of cardiovascular disease independently. Therefore, it is speculated that the cardiovascular protective effect of exercise is also related to its ability to regulate the concentrations of irisin and exosomes in the circulatory system. In this review, the potential synergistic interactions between irisin and exosomes are examined, as well as the underlying mechanisms including the AMPK/PI3K/AKT pathway, the TGFß1/Smad2/3 pathway, the PI3K/AKT/VEGF pathway, and the PTEN/PINK1/Parkin pathway are examined. This paper provides evidence to propose that exercise promotes the release of exosomes enriched with irisin, miR-486-5p and miR-342-5p from skeletal muscles, which results in the activation protective networks in the cardiovascular system. Moreover, the potential synergistic effect in exosomal cargo can provide new ideas for clinical research of exercise mimics.

Macrophage-Derived Exosomes as Advanced Therapeutics for Inflammation: Current Progress and Future Perspectives.

The development of numerous diseases is significantly influenced by inflammation. Macrophage-derived exosomes (M-Exos) play a role in controlling inflammatory reactions in various conditions, including chronic inflammatory pain, hypertension, and diabetes. However, the specific targets and roles of M-Exos in regulating inflammation in diseases remain largely unknown. This review summarizes current knowledge on M-Exos biogenesis and provides updated information on M-Exos' biological function in inflammation modulation. Furthermore, this review highlights the functionalization and engineering strategies of M-Exos, while providing an overview of cutting-edge approaches to engineering M-Exos and advancements in their application as therapeutics for inflammation modulation. Finally, multiple engineering strategies and mechanisms are presented in this review along with their perspectives and challenges, and the potential contribution that M-Exos may have in diseases through the modulation of inflammation is discussed.

Electroacupuncture improving obesity-induced insulin resistance via regulating intestinal SIRT1/TLR4 signaling pathway. / ç”µé’ˆè°ƒæŽ§å°è‚ æ²‰é»˜ä¿¡æ¯è°ƒèŠ‚å› å­1/Tollæ ·å—ä½“4ç‚Žæ€§é€šè·¯æ”¹å–„è‚¥èƒ–å¤§é¼ èƒ°å²›ç´ æŠµæŠ—çš„æœºåˆ¶ç ”ç©¶.

OBJECTIVES: To observe the effect of electroacupuncture (EA) in obese rats with insulin resistance (IR) through regulating intestinal silent information regulator 1 (SIRT1)/Toll-like receptor 4 (TLR4) signaling pathway, so as to explore the underlying mechanism of EA in improving obesity-induced IR. METHODS: A total of 40 Wistar rats were randomly divided into 4 groups, i.e. normal group, model group, EA group and EA combined with inhibitor group, with 10 rats in each group. The obesity-induced IR model was induced by feeding high-fat diet for 8 weeks. EA (2 Hz, 1mA) was applied at "Zhongwan"(CV12), "Guanyuan"(CV4), "Zusanli"(ST36) and "Fenglong" (ST40) for 10 min, 3 times a week for 8 weeks in both EA and EA combined with inhibitor groups. Sirtinol, an inhibitor of SIRT1 was injected into the tail vein (1 mg/kg), 3 times a week for 8 weeks in EA combined with inhibitor group. The body weight, glucose infusion rate (GIR) of rats in each group were recorded. The contents of serum C-reactive protein (CRP), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and lipopolysaccharide (LPS) were detected by ELISA. Mucosal morphological changes in the small intestine was observed by HE staining and was graded using Chiu's score. The protein relative expression levels of SIRT1 and TLR4 and the co-labeling of SIRT1 with TLR4 in the small intestine was detected by Western blot and double immunofluorescence staining, separately. RESULTS: Compared with the normal group, the body weight, serum contents of CRP, TNF-α, IL-6, LPS, Chiu's score, TLR4 protein relative expression level and percentage of TLR4 positive expression area were increased (P<0.01, P<0.05), while the GIR, SIRT1 protein expression, percentage of SIRT1 positive expression area and SIRT1/TLR4 were decreased (P<0.01) in the model group. The pathological injury of small intestine mucosa was severe, accompanied with inflammatory cell infiltration in the model group. Following interventions, the body weight, serum contents of CRP, TNF-α and LPS, Chiu's score, TLR4 protein relative expression level and percentage of TLR4 positive expression area were decreased(P<0.01, P<0.05), and the GIR was increased (P<0.01), the pathological injury and inflammatory cell infiltration of small intestine mucosa were reduced in both EA and EA combined with inhibitor groups in contrast to the model group. Compared with the model group, the serum IL-6 content was significantly decreased (P<0.01), and the SIRT1 protein relative expression level and percentage of positive expression area, SIRT1/TLR4 were increased (P<0.01, P<0.05) in the EA group. Compared with the EA group, EA combined with inhibitor group showed the body weight, serum CRP, IL-6, LPS, Chiu's score, TLR4 protein relative expression level and TLR4 positive expression area were increased (P<0.01, P<0.05), and the GIR level , SIRT1 relative expression level, SIRT1/TLR4 ratio were decreased (P<0.05, P<0.01). CONCLUSIONS: EA can reduce the body weight and ameliorate peripheral insulin sensitivity in IR obese rats, which may be related with its function in regulating intestinal SIRT1/TLR4 signaling pathway to reduce inflammatory response.

Comparative efficacy of acupuncture-related therapy for migraine: A systematic review and network meta-analysis.

Background: Migraine is a worldwide disabling chronic brain disorder, some studies suggest acupuncture-related therapy plays an important role in raising efficiency rates and reducing migraine attacks. However, clinical trials comparing the efficacy of different interventions for migraine are limited and controversial. This network meta-analysis (NMA) was performed to review all randomized controlled trials (RCTs) comparing the effects of acupuncture-related therapy for migraine. Methods: Randomized controlled trials (RCTs) of acupuncture-related therapy for migraine were searched in the following databases from the date of database inception to March 31, 2022, including PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure (CNKI), VIP Database, Wanfang Database, and Chinese Biomedical Database (CBM). The primary endpoint was visual analog scale (VAS) scores. The secondary endpoints were the number of migraine days, duration of migraine, and frequency of migraine attacks. We used Cochrane risk of bias to assess the quality of evidence for outcomes. Results: Thirty-nine studies involving 4379 patients with 13 different acupuncture-related methods were evaluated. According to surface under the cumulative ranking curve value, acupoint injection was ranked the highest (98.0%) in VAS scores, followed by acupoint implantation (79.0%); electroacupuncture was the optimal intervention method (82.4%) in the number of migraine days, followed by embedding needle therapy (73.1%); embedding needle therapy ranked first (99.9%) in the duration of migraine, followed by acupoint injection (77.4%); acupoint injection was the best intervention (99.3%) in the frequency of migraine attacks, followed by conventional acupuncture plus massage (73.8%). Conclusion: These results provide preliminary evidence that acupuncture-related therapy could be recommended as one of the effective treatments for migraine. Conventional acupuncture has significant effects on improving VAS scores, the number of migraine days, duration of migraine, and frequency of migraine attacks. However, more high-quality studies should be carried out to verify this finding. Systematic review registration: https://inplasy.com/, identifier: INPLASY202110035.

HDAC3 deteriorates colorectal cancer progression via microRNA-296-3p/TGIF1/TGFß axis.

BACKGROUND: The mechanism of histone deacetylase 3 (HDAC3) in colorectal cancer (CRC) has already been discussed. However, the feedback loop of HDAC3/microRNA (miR)-296-3p and transforming growth factor ß-induced factor 1 (TGIF1) in CRC has not been explained clearly. Thus, the mainstay of this study is to delve out the mechanism of this axis in CRC. METHODS: To demonstrate that HDAC3 regulates the miR-296-3p/TGIF1/TGFß axis and is involved in CRC progression, a series of cell biological, molecular and biochemical approaches were conducted from the clinical research level, in vitro experiments and in vivo experiments. These methods included RT-qPCR, Western blot assay, cell transfection, MTT assay, EdU assay, flow cytometry, scratch test, Transwell assay, dual luciferase reporter gene assay, chromatin immunoprecipitation, nude mouse xenograft, H&E staining and TUNEL staining. RESULTS: Higher HDAC3 and TGIF1 and lower miR-296-3p expression levels were found in CRC tissues. HDAC3 was negatively connected with miR-296-3p while positively correlated with TGIF1, and miR-296-3p was negatively connected with TGIF1. Depleted HDAC3 elevated miR-296-3p expression and reduced TGIF1 expression, decreased TGFß pathway-related proteins, inhibited CRC proliferation, invasion, and migration in vitro and slowed down tumor growth and induction of apoptosis in vivo, which were reversed by miR-296-3p knockdown. Restored miR-296-3p suppressed TGIF1 and reduced TGFß pathway-related proteins, inhibited CRC proliferation, invasion, and migration in vitro and slowed down tumor growth and induction of apoptosis in vivo, which were reversed by TGIF1 overexpression. CONCLUSION: This study illustrates that down-regulation of HDAC3 or TGIF1 or up-regulation of miR-296-3p discourages CRC cell progression and slows down tumor growth, which guides towards a novel direction of CRC treatment.

[Immediate effect of acupuncture and moxibustion at Guanyuan (CV 4) and Zusanli (ST 36) on heart rate variability in patients with qi deficiency syndrome].

OBJECTIVE: To compare the immediate effect of acupuncture and moxibustion at Guanyuan (CV 4) and Zusanli (ST 36) on heart rate variability index in patients with qi deficiency syndrome. METHODS: Ninety patients with qi deficiency syndrome were randomly divided into an acupuncture group, a moxibustion group and a blank group, 30 patients in each group. The patients in the acupuncture group were treated with acupuncture at Guanyuan (CV 4) and Zusanli (ST 36) for 15 min; acupuncture was given once. The patients in the moxibustion group were treated with moxibustion with identical acupoints and treatment duration. The patients in the blank group received no intervention. The symptom scores of qi deficiency syndrome in each group before and after treatment were recorded. The average heart rate and index of heart rate variability including total power, low frequency (LF), high frequency (HF) and logarithm of LF/HF (log LF/HF) were tested 5 min before treatment, 5 min, 10 min, 15 min into treatment, and 5 min after treatment. RESULTS: The symptom scores of qi deficiency syndrome were reduced in the acupuncture group and moxibustion group after treatment (P<0.05). Compared before treatment, in the acupuncture group, the HF was increased 5 min into treatment (P<0.05), but was reduced 15 min into treatment and 5 min after treatment (P<0.05, P<0.01). The log LF/HF was increased 5 min and 10 min into treatment and 5 min after treatment (P<0.01). The difference of average heart rate between 5 min before treatment and 5 min after treatment in the acupuncture group was higher than that in the moxibustion group and blank group (P<0.05), and the difference of log LF/HF was higher than that in the moxibustion group and blank group (P<0.05, P<0.01). CONCLUSION: Acupuncture and moxibustion has immediate effects on heart rate variability in patients with qi deficiency syndrome, and the effect of acupuncture is superior to moxibustion, which may be related to the benign regulation of acupuncture on autonomic nervous system.

[Electroacupuncture improves inflammatory reaction and insulin sensitivity in insulin-resistant obese rats].

OBJECTIVE: To observe the effect of electroacupuncture (EA) on inflammatory reaction and insulin sensitivity in insulin-resistant obese (OIR) rats. METHODS: Thirteen male Wistar rats were randomly selected as the control group and fed with common diet. The other 39 rats were fed with high-fat diet for 8 weeks to establish OIR model and then randomized into model, EA and sham EA groups. EA (2 Hz, 1 mA) was applied to unilateral "Zusanli" (ST36), "Fenglong" (ST40), "Zhongwan" (CV12) and "Guanyuan" (CV4) for 15 min, once every other day for 8 weeks, and sham EA was applied to unilateral 4 control spots about 5 mm lateral to the aforementioned 4 acupoints after shallowly inserting acupuncture needles, but without electric current output. After 8 weeks' intervention, the body weight was recorded and the glucose infusion rate (GIR) measured using hyperinsulinemic-euglycemic clamp technique. At the 6th week of intervention, glucose contents of intraperitoneal glucose tolerance test (IPGTT) and intraperitoneal insulin tole-rance test (IPITT) were measured. The levels of serum insulin (INS) and inflammatory factors as C-reactive protein (CRP), IL-6 and TNF-α were measured by using ELISA at the end of the treatment. The expression levels of IL-6, TNF-α, monocyte chemoattractant protein-1(MCP-1), IL-10 and IL-1ß proteins and mRNAs in the abdominal adipose tissues were detected by Western blot and quantitative real time-PCR, separately. The CD68 expression (displaying infiltration of macrophages) of adipose tissue was detected using immunohistochemistry. RESULTS: After modeling, the contents of glucose of IPGTT at 30, 60 and 120 min and those of IPITT at 15, 30, 60 and 120 min, serum INS, CRP, IL-6 and TNF-α, as well as the expression levels of IL-6, TNF-α, IL-1ß and MCP-1 proteins and mRNAs and CD68 protein were significantly increased (P<0.01, P<0.05), while the levels of GIR and IL-10 protein and mRNA were obviously decreased in the model group in comparison with those of the control group (P<0.01), suggesting an increase of inflammation and a decline of INS sensitivity. Following the interventions, the increased contents of glucose of IPGTT and IPITT, serum INS, CRP, IL-6 and TNF-α, expression levels of IL-6, TNF-α, IL-1ß and MCP-1 proteins and mRNAs and CD68 protein, and the decreased levels of GIR and IL-10 protein and mRNA were evidently reversed in the EA group compared with the model group (P<0.01, P<0.05) rather than those in the sham EA group (P>0.05). CONCLUSION: EA can reduce the level of inflammation and improve insulin sensitivity in OIR rats.

[Network meta-analysis on the effects of the acupuncture-related therapy on ovulation rate and pregnancy rate in patients with polycystic ovary syndrome].

OBJECTIVE: To review systematically the safety and effectiveness of acupuncture-related therapies on ovulation rate and pregnancy rate in patients with polycystic ovary syndrome (PCOS). METHODS: From PubMed, EMbase, the Cochrane Library, China Biology Medicine disc (CBM), China National Knowledge Infrastructure (CNKI), Wanfang database and VIP database, the randomized controlled trials (RCTs) on PCOS were retrieved in the period from the date of database establishment to January 8, 2018. Two researchers screened the articles, extracted the data and assessed the bias risk of the eligible trials independently. Using Stata 13.0 and WinBUGS 1.4.3 software, the data were analyzed. RESULTS: A total of 39 RCTs were collected, including 4605 cases of PCOS and 14 kinds of acupuncture-related therapies and the comprehensive therapies. The short-term therapeutic effects were observed. The results of mesh meta-analysis showed: regarding the ovulation rate, the effects of the acupuncture-medication therapy were better than western medication. The top 6 therapeutic measures were the treatment with acupoint thread-embedding therapy and medication (93.3%), the treatment with moxibustion and Chinese herbal medicine (91.4%), moxibustion (74.5%), the treatment with acupuncture and medication (65.7%), the treatment with acupuncture-moxibustion and auricular point therapy (61.9%) and the treatment with acupuncture and auricular point therapy (49.6%). Regarding the pregnancy rate, the effects of the acupuncture-medication therapy were better than western medication. The top 6 therapeutic measures were the treatment with acupuncture and auricular point therapy (91.5%), the treatment with moxibustion and Chinese herbal medication (86.9%), the treatment with acupuncture-moxibustion and auricular point therapy (81.1%), the treatment with acupoint thread-embedding therapy and medication (69.4%), the treatment with acupuncture and medication (66.1%) and the treatment with placebo and western medication (58.7%). CONCLUSION: Among acupuncture-related therapies, the combined treatment is more advantageous than single therapy and its safety is superior to western medication. The combined therapies are various in advantages. Because of the limitation of the present researches, it needs a large scale of RCTs with rational design, high quality and proper methods to verify this research conclusion.

Fabrication of chitosan/Au-TiO2 nanotube-based dry electrodes for electroencephalography recording.

In this paper, we describe a method for fabricating dry electrodes for use in recording electroencephalograms (EEGs), which are based on the use of chitosan (Ch), gold (Au) particles, and titanium dioxide (TiO2) nanotube arrays deposited on titanium (Ti) thin sheets. The samples were characterized by scanning electron microscopy, X-ray diffraction, electrochemical impedance spectroscopy, and EEG signal collection. The TiO2 nanotube arrays were grown on the Ti thin sheet by an electrochemical anodic oxidation method. The Au particles were deposited on the bottom and surface layers of the TiO2 nanotube array using an electrochemistry-based multi-potential step technology. The fabricated dry Ch/Au-TiO2 electrodes have an efficient conversion interface for ion current/electron current, a high biocompatible contact surface, and a fast electron transfer channel. To confirm that the Ch/Au-TiO2 layer can be used in dry EEG electrodes, the impedance spectra of the electrodes in solution and skin were analyzed. The mean impedance values for skin were found to be approximately 169±33.0kΩ at 2.15Hz and 67.4±8.9kΩ at 100Hz. In addition, EEG signals from the forehead and sites with hair were collected using both the dry Ch/Au-TiO2 electrode and a wet Ag/AgCl electrode for comparison purposes. It was found that high quality EEG signal recordings could be obtained using the dry electrodes. The fact that electrolytes are not required means that the electrodes are suitable for use in long-term bio-potential testing.