Influence of hypothyroidism on testicular mitochondrial oxidative stress by activating the p38 mitogen-activated protein kinase and c-Jun NH2-terminal kinase signaling pathways in rats.

Thyroid hormone deficiency can impair testicular function. However, knowledge of the effects of mitogen-activated protein kinase (MAPK) pathways on testicular mitochondrial oxidative damage induced by hypothyroidism is still rudimentary. This study aims to explore the possible mechanisms of testicular mitochondrial oxidative damage in hypothyroidism rats. Wistar male rats were randomly divided into control (C), low- (L), and high-hypothyroidism (H) groups (1 ml/100 g body weights (BWs)/day 0, 0.001% and 0.1% propylthiouracil, respectively) by intragastric gavage for 60 days. Blood samples were collected to measure the levels of serum triiodothyronine (T3), thyroxine (T4), and thyroid stimulating hormone (TSH). Testicular mitochondrial homogenates were used to measure the activities of superoxide dismutase (SOD), catalase (CAT), and Ca2+-ATPase as well as protein and mRNA expression of androgen receptor (AR), p38 MAPK, and c-Jun NH2-terminal kinase (JNK). Results showed that the BWs, testes weights, and levels of T3 and T4 were all significantly decreased and the testes coefficient and level of TSH were significantly increased in the H group. There were significant decreases in SOD activity in the H group as well as decreases in CAT and Ca2+-ATPase activities in the L and H groups. Additionally, protein expression of AR decreased significantly and protein expression of phosphorylated p38MAPK and JNK increased significantly in the H group. Therefore, the study suggests that hypothyroidism could affect male reproductive function by disturbing expression of AR, changing the activity of Ca2+-ATPase, inducing oxidative stress and then leading to activation of p38MAPK and JNK signaling in the testicular mitochondria.

Electroacupuncture for patients with refractory functional dyspepsia: A randomized controlled trial.

BACKGROUND: To test the efficacy of electroacupuncture for patients with refractory functional dyspepsia (FD). METHODS: A 24-week, 2-arm, single-blind, randomized controlled trial was conducted at three hospitals in China. Patients with refractory FD were randomly assigned to receive 20 sessions of authentic or sham electroacupuncture in a treatment duration of 4 weeks. The primary outcome was complete absence of dyspeptic symptoms at 16 weeks after initiation of acupuncture (week 16). The secondary outcomes included adequate relief of dyspeptic symptoms, Leeds Dyspepsia Questionnaire (LDQ), Nepean Dyspepsia Index (NDI), and adverse events. Intention-to-treat analysis was performed. KEY RESULTS: Two hundred patients were included, of which 196 (98%) completed follow-up data at week 24. At week 16, 17 (17%) patients in the authentic electroacupuncture group vs 6 (6%) patients in the sham group achieved the primary outcome (P = .014). Sixty-two (62%) patients had adequate relief in the authentic electroacupuncture group, as compared to 22 (22%) in the sham group (P = .001). The scores of LDQ and NDI were significantly improved in both groups at week 16, and patients in the authentic electroacupuncture group have more improvements (LDQ, mean difference, -2.2, 95% confidence interval, -2.3 to -2.1, P < .001; NDI, -7.3, -10.5 to -4.2, P < .001). Results were similar for all the outcomes assessed at week 24. No serious adverse events were reported in both groups. CONCLUSION: Acupuncture efficaciously improves dyspeptic symptoms in patients with refractory FD.

Effect of electroacupuncture on the cervicospinal P2X7 receptor/fractalkine/CX3CR1 signaling pathway in a rat neck-incision pain model.

Increasing evidence supports that acupuncture intervention is an effective approach for intraoperative and postoperative pain. Neuron-microglia crosstalk, mediated by the purinergic P2X7 receptor (R)/fractalkine/CX3CR1 cascade in the spinal cord dorsal horn, plays a pivotal role in pain processing. However, its involvement in the analgesic effect of electroacupuncture (EA) remains unclear. In this study, a rat neck-incision pain model was established by making a longitudinal incision along the midline of the neck and subsequent repeated mechanical stimulation. EA stimulation was applied to bilateral LI18, LI4-PC6, or ST36-GB34. The thermal pain threshold, cervicospinal ATP concentration, expression levels of purinergic P2XR and P2YR subunits mRNAs, and fractalkine, CX3CR1 and p38 MAPK proteins, were detected separately. The neck incision induced strong thermal hyperalgesia and upregulation of spinal ATP within 48 h. No significant change was found in thermal hyperalgesia after a single session of EA intervention. However, a single session of EA dramatically enhanced the neck incision-induced upregulation of ATP and upregulated the expression of P2X7R, which was reversed by two sessions of EA. Two sessions of EA at bilateral LI18 or LI4-PC6 attenuated hyperalgesia significantly, accompanied with downregulation of P2X7R/fractalkine/ CX3CR1 signaling after three sessions of EA. EA stimulation of LI18 or LI4-PC6 alleviates thermal hyperalgesia in neck-incision pain rats, which may be associated with its effects in regulating the neck incision-induced increase of ATP and P2X7R and subsequently suppressing fractalkine/CX3CR1 signaling in the cervical spinal cord.

Randomised clinical trial: an assessment of acupuncture on specific meridian or specific acupoint vs. sham acupuncture for treating functional dyspepsia.

BACKGROUND: Functional dyspepsia (FD) is a common disease without an established optimal treatment. AIM: To determine (i) the effect of acupuncture in relieving FD symptoms and improving life quality; (ii) the effect difference between acupoint and non-acupoint; and (iii) the effect difference among different acupoints. METHODS: A total of 712 eligible patients were included and randomly assigned to six groups (Group A: specific acupoints of the stomach meridian; Group B: non-specific acupoints of the stomach meridian; Group C: specific acupoints of alarm and transport points; Group D: specific acupoints of the gallbladder meridian; Group E: sham acupuncture of non-acupoints; and Group F: itopride). A treatment period of 4 weeks (continuous five sessions per week), and a follow-up period of 12 weeks were arranged. The outcomes were the (i) patients' response, (ii) symptoms improvement measured using the Symptom Index of Dyspepsia and (iii) quality-of-life improvement based on Nepean Dyspepsia Index. RESULTS: All groups had an improvement in dyspepsia symptoms and the QoL at the end of treatment, and the improvement was sustained for 4 weeks and 12 weeks. The overall response rate was significantly higher in acupuncture group A (70.69%), and lower in sham acupuncture group (34.75%), compared with itopride and other acupuncture groups. Similarly, the difference in symptoms and QoL improvement was significant between group A and the other acupuncture groups. CONCLUSIONS: Acupuncture is effective in the treatment of functional dyspepsia, and is superior to non-acupoint puncture. The benefit of acupuncture relies on acupoint specificity.