Heart-targeting exosomes from human cardiosphere-derived cells improve the therapeutic effect on cardiac hypertrophy.

Exosomes of human cardiosphere-derived cells (CDCs) are very promising for treating cardiovascular disorders. However, the current challenge is inconvenient delivery methods of exosomes for clinical application. The present study aims to explore the potential to enhance the therapeutic effect of exosome (EXO) from human CDCs to myocardial hypertrophy. A heart homing peptide (HHP) was displayed on the surface of exosomes derived from CDCs that were forced to express the HHP fused on the N-terminus of the lysosomal-associated membrane protein 2b (LAMP2b). The cardiomyocyte-targeting capability of exosomes were analyzed and their therapeutic effects were evaluated in a mouse model of myocardial hypertrophy induced by transverse aorta constriction (TAC). The molecular mechanisms of the therapeutic effects were dissected in angiotensin II-induced neonatal rat cardiomyocyte (NRCMs) hypertrophy model using a combination of biochemistry, immunohistochemistry and molecular biology techniques. We found that HHP-exosomes (HHP-EXO) accumulated more in mouse hearts after intravenous delivery and in cultured NRCMs than control exosomes (CON-EXO). Cardiac function of TAC mice was significantly improved with intravenous HHP-EXO administration. Left ventricular hypertrophy was reduced more by HHP-EXO than CON-EXO via inhibition of ß-MHC, BNP, GP130, p-STAT3, p-ERK1/2, and p-AKT. Similar results were obtained in angiotensin II-induced hypertrophy of NRCMs, in which the beneficial effects of HHP-EXO were abolished by miRNA-148a inhibition. Our results indicate that HHP-EXO preferentially target the heart and improve the therapeutic effect of CDCs-exosomes on cardiac hypertrophy. The beneficial therapeutic effect is most likely attributed to miRNA-148a-mediated suppression of GP130, which in turn inhibits STAT3/ERK1/2/AKT signaling pathway, leading to improved cardiac function and remodeling.

Acacetin alleviates myocardial ischaemia/reperfusion injury by inhibiting oxidative stress and apoptosis via the Nrf-2/HO-1 pathway.

CONTEXT: Acacetin is a natural source of flavonoids with anti-inflammatory and antioxidant effects. OBJECTIVE: This study determines acacetin's protective effect and mechanism on myocardial ischaemia/reperfusion (I/R) injury. MATERIALS AND METHODS: Sprague-Dawley rats were divided into sham and I/R injury and treatment with acacetin. Acacetin (10 mg/kg) was subcutaneously injected for 7 days. ECG and echocardiography were conducted to determine arrhythmia and heart function. The pathological characters of the heart were determined with triphenyl tetrazolium chloride staining, Haematoxylin & Eosin staining, and Masson staining. Expression of proteins in infarct tissues was examined with western blots. RESULTS: Administrated with acacetin in I/R rats significantly reduced the arrhythmia score from 4.90 to 2.50 and the reperfusion arrhythmia score from 3.79 to 1.82 in the vehicle or the acacetin group, respectively. LVEF was improved from 33.5% in the I/R group to 43.7% in the acacetin group, LVFS was increased from 16.4% to 24.5%, LVIDs was decreased from 6.5 to 5.3 mm. The inflammatory cell infiltration, myocardial fibrosis, and collagen 1 and 3 were reduced by acacetin. Acacetin promoted SOD and decreased MDA. In myocardial tissues, the expression level of TLR4 and IL-6 were restrained, and IL-10 was promoted. Apoptotic protein Bax was suppressed, and anti-apoptotic protein Bcl-2 was promoted in the acacetin group. Interestingly, the transcription factor Nrf-2/HO-1 pathway was also reversed by acacetin. DISCUSSION AND CONCLUSION: Our findings indicated that acacetin has a potential therapeutic effect in clinical application on treating I/R-induced heart injury.

[Effect of abdominal penetrating moxibustion on function of core muscle group in stroke patients based on surface electromyography].

OBJECTIVE: To observe the effect of abdominal penetrating moxibustion on strength and endurance of core muscle group in patients with stroke. METHODS: Sixty-two patients with stroke were randomly divided into an observation group (31 cases, 2 cases dropped off) and a control group (31 cases, 2 cases dropped off). The patients in the control group were treated with routine basic treatment, acupuncture treatment and rehabilitation training; based on the treatment of the control group, the patients in the observation group were treated with abdominal penetrating moxibustion, approximately 50 min each time, once a day. The treatments in the two groups were given 5 times a week for 4 weeks. The root mean square (RMS) and median frequency (MF) of bilateral transverse abdominis and multifidus of performing sitting-standing and making steps were measured by surface electromyography before and after treatment. The postural assessment scale for stroke (PASS), Berg balance scale (BBS) and lower-limb Fugl-Meyer motor assessment (FMA) scores were observed before treatment, 2 weeks into treatment and 4 weeks into treatment. RESULTS: Compared before treatment, when performing different postures, the RMS and MF of bilateral transversus abdominis and multifidus in the two groups were increased after treatment (P<0.01, P<0.05). The RMS of affected-side transversus abdominis and multifidus and the MF value of bilateral transverse abdominis and multifidus in the observation group were higher than those in the control group (P<0.05). Compared before treatment, the PASS, BBS and FMA scores were increased 4 weeks into treatment in the two groups (P<0.01), and those in the observation group were higher than the control group (P<0.01). CONCLUSION: The abdominal penetrating moxibustion could effectively improve the strength and endurance of core muscle group, improve the posture control, balance ability and lower-limb motor function in patients with stroke.

[Effect of electronic moxibustion on activity of parapharyngeal wall in patients with achalasia of cricopharyngeus muscle after stroke based on musculoskeletal ultrasound].

OBJECTIVE: To observe the clinical effect of electronic moxibustion on dysphagia in patients with achalasia of cricopharyngeus muscle after stroke. METHODS: Sixty patients with dysphagia of achalasia of cricopharyngeus muscle were randomly divided into an observation group and a control group, 30 cases in each group. One patient in the observation group and 2 cases in the control group dropped off. The patients in the control group were treated with routine medical treatment, acupuncture treatment and swallowing rehabilitation training; the patients in the observation group were additionally treated with electronic moxibustion at Lianquan (CV 23), Tiantu (CV 22), Tianding (LI 17) and Futu (LI 18), 30 min each treatment. Both groups were treated 5 times a week for 4 weeks. The musculoskeletal ultrasound (MSUS) was applied to test the activity of parapharyngeal wall and the dysphagia score of Ichiro Fujishima was compared before and after 4-week treatment. RESULTS: After treatment, the activity of the parapharyngeal wall and the dysphagia score of Ichiro Fujishima were increased in both groups (P<0.01, P<0.05). The changes of activity of parapharyngeal wall and dysphagia score of Ichiro Fujishima in the observation group were greater than the control group (P<0.05, P<0.01). CONCLUSION: Electronic moxibustion can improve the impaired swallowing function and reconstruct the normal swallowing process.

[Effect of jiaotong qiaomai needling technique of acupuncture on the morphology of lower limb muscle based on muscle-skeleton ultrasound measurement in patients with post-stroke strephenopodia].

OBJECTIVE: To evaluate the therapeutic effect on post-stroke strephenopodia treated with jiaotong qiaomai (harmonizing the heel vessel) needling technique of acupuncture. METHODS: A total of 64 patients were randomized into an observation group (30 cases included, 2 cases dropped off) and a control group (30 cases included, 2 cases dropped off). In the control group, the routine needling technique of acupuncture and rehabilitation exercise were provided. In the observation group, on the base of the therapeutic regimen as the control group, the jiaotong qiaomai needling technique of acupuncture was added. Fengchi (GB 20), Rangu (KI 2), Zhaohai (KI 6) on the affected side and Fengfu (GV 16) were selected. The treatment was given once daily, 5 times a week, for 4 weeks totally in either group. Separately, before treatment, in 2 weeks and 4 weeks of treatment, the strephenopodia angle was measured and Holden functional ambulation classification (FAC) was evaluated in the patients. Additionally, before treatment and in 4 weeks of treatment, the muscle-skeleton ultrasound was adopted to measure the thickness of anterior tibia muscle and posterior tibia muscle in the resting state of the patients. RESULTS: The strephenopodia angle and Holden FAC were all improved after 4-week treatment in the two groups as compared with those before treatment (P<0.01, P<0.05), and the results in the observation group were better than those in the control group (P<0.01, P<0.05). Before treatment, the thickness of anterior tibia muscle and posterior tibia muscle on the healthy side was higher than that on the affected side in the patients of the two groups (P<0.05). After treatment, the thickness of anterior tibia muscle and posterior tibia muscle on the affected side was increased as compared with that before treatment in the two groups (P<0.01, P<0.05). The thickness on the healthy side was similar before and after treatment in the observation group (P>0.05), and it was increased on the healthy side after treatment as compared with that before treatment in the control group (P<0.05). After treatment, the thickness of anterior tibia muscle and posterior tibia muscle on the affected side was similar to that on the healthy side in the two groups (P>0.05), and the thickness on the affected side in the observation group was higher than that in the control group after treatment (P<0.05). CONCLUSION: The jiaotong qiaomai needling technique of acupuncture effectively improves the strephenopodia angle and ambulation function, as well as the morphology of anterior tibia muscle and posterior tibia muscle in the patients with post-stroke strephenopodia.

[Effect of SU Jia-fu's Wenjing Tongdu external treatment combined with long-snake moxibustion at governor vessel on urodynamic for neurogenic bladder after spinal cord injury].

OBJECTIVE: To observe the clinical efficacy of SU Jia-fu's Wenjing Tongdu external treatment combined with long-snake moxibustion at the governor vessel for neurogenic bladder after spinal cord injury. METHODS: A total of 64 patients with neurogenic bladder after spinal cord injury were randomly divided into an observation group and a control group, 32 cases in each group. The patients in the control group were treated with routine acupuncture and rehabilitation of bladder function; based on the treatment in the control group, the patients in the observation group were treated with SU Jia-fu's Wenjing Tongdu external treatment combined with long-snake moxibustion at the governor vessel, twice a week for 8 weeks. Urodynamic test, including residual urine volume (RUV), maximum flow rate of urination (Qmax), bladder pressure at filling phase (Pves), maximum detrusor pressure (Pdet-max) and maximum urinary bladder volume (VMCC), was performed before and after 8-week treatment. RESULTS: The urodynamic indexes in the two groups were improved compared with before treatment (P<0.01, P<0.05); after treatment, VMCC in the observation group was significantly higher than the control group (P<0.01), while RUV and Pves in the observation group were significantly lower than the control group (P<0.05). After treatment, there was no significant difference in Qmax and Pdet-max between the two groups (P>0.05). CONCLUSION: Based on routine acupuncture and rehabilitation of bladder function, SU Jia-fu's Wenjing Tongdu external treatment combined with long-snake moxibustion at the governor vessel could effectively improve urodynamic indexes, reduce residual urine, reduce bladder pressure and increase the maximum capacity of bladder, thereby improving bladder compliance and bladder function.

[Levels of amino acids in cerebral spinal fluid in children with cerebral palsy].

OBJECTIVE: To study the changes of amino acids in cerebral spinal fluid (CSF) in children with spastic or athetotic cerebral palsy (CP) by examining CSF levels of glutamic acid (Glu), gamma-aminobutyric acid (GABA) and aspartate (ASP). METHODS: CSF samples were obtained from 13 children with spastic CP, from 14 children with athetotic CP, and from 10 children without central nervous system and infectious diseases (control group). CSF levels of Glu, GABA and ASP were determined by high-performance liquid chromatography. RESULTS: CSF levels of GABA, ASP and Glu in the control group were 13.04+/-2.19, 10.21+/-0.45 and 8.41+/-2.26 micromol/L, respectively. Compared with the control group, CSF GABA levels in the spastic and the athetotic CP groups (8.02+/-2.03 and 10.01+/-2.68 micromol/L respectively) significantly decreased (P<0.01), whereas CSF levels of Glu (20.99+/-8.15 and 28.77+/-17.62 micromol/L respectively) and Asp (13.53+/-3.93 and 14.02+/-2.88 micromol/L respectively) in the spastic and the athetotic CP groups significantly increased (P<0.01). There were statistical differences in the GABA level between the spastic and the athetotic CP groups (P<0.05). In children with spastic CPCSF Glu level was positively correlated to muscle tension. CONCLUSIONS: CSF excitatory amino acid levels increased, while CSF inhibitory amino acid levels decreased in children with CP. There were differences for CSF amino acid levels in different types of CP. The changes of amino acid levels may contribute to the pathogenesis of CP.

Using 3D MRI can potentially enhance the ability of trained surgeons to more precisely diagnose Mullerian duct anomalies compared to MR alone.

OBJECTIVE: The aim of this study was to examine if the advanced tool of 3D MRI model provides more precise information on the anatomy of pelvic organs than MRI alone, and compare to clinical and operative finding of patients with vagina in Müllerian duct anomalies. STUDY DESIGN: One hundred and ten patients with clinically and operatively proven Müllerian duct anomalies were included. The consistency of diagnosis of Mullerian tract anomalies by MRI and 3D MRI compared to clinically and surgically proven anomalies defined according to ASRM classification. RESULTS: We successfully reconstructed retrospectively all 110 patients' three-dimensional models from the simple MRI scans. Eighty-six of the patients (78.2%) showed an agenesis of the uterus, four patients presented with uterine didephys (3.6%). Septate uterus was detectable in 8 of 110 cases (7.3%). Arcuate uterus was detectable in 3 of 110 cases (2.7%). The remaining patients presented with either unilateral (n = 4; 3.6%) or bilateral (n = 5; 4.5%) uterine horns. Reviewed by radiologists, comparing the agreement rate between 3D- MRI reconstruction models and simple MRI, there was a trend towards but not significant difference (P = 0.064). Reviewed by trained surgeons, the agreement between three-dimensional MRI reconstruction models and MRI, there was significant difference (P = 0.003). CONCLUSION: 3D MRI model is a non-expensive add-on software tool that enhance the ability of expert surgeon to reach a more precise diagnosis of the pelvic anatomy structures, compared to MRI alone. Getting a more precise description of the pelvic anatomy allows a better planning of the corrective procedure needed and preoperative assessment of the expected prognosis.