Histone deacetylases (HDACs) are a family of enzymes that mediate nucleosomal histone deacetylation and gene expression. Some members of the HDAC family have also been implicated in nonhistone protein deacetylation, which modulates cell-cycle control, differentiation, and cell migration. However, the role of HDACs in smooth muscle contraction is largely unknown. Here, HDAC8 was localized both in the cytoplasm and the nucleus of mouse and human smooth muscle cells. Knockdown of HDAC8 by lentivirus-encoding HDAC8 shRNA inhibited force development in response to acetylcholine. Treatment of smooth muscle tissues with HDAC8 inhibitor XXIV (OSU-HDAC-44) induced relaxation of precontracted smooth muscle tissues. In addition, cortactin is an actin-regulatory protein that undergoes deacetylation during migration of NIH 3T3 cells. In this study, acetylcholine stimulation induced cortactin deacetylation in mouse and human smooth muscle tissues, as evidenced by immunoblot analysis using antibody against acetylated lysine. Knockdown of HDAC8 by RNAi or treatment with the inhibitor attenuated cortactin deacetylation and actin polymerization without affecting myosin activation. Furthermore, expression of a charge-neutralizing cortactin mutant inhibited contraction and actin dynamics during contractile activation. These results suggest a novel mechanism for the regulation of smooth muscle contraction. In response to contractile stimulation, HDAC8 may mediate cortactin deacetylation, which subsequently promotes actin filament polymerization and smooth muscle contraction.

Polo-like kinase 1 (Plk1) is a serine/threonine-protein kinase that has been implicated in mitosis, cytokinesis, and smooth muscle cell proliferation. The role of Plk1 in smooth muscle contraction has not been investigated. Here, stimulation with acetylcholine induced Plk1 phosphorylation at Thr-210 (an indication of Plk1 activation) in smooth muscle. Contractile stimulation also activated Plk1 in live smooth muscle cells as evidenced by changes in fluorescence resonance energy transfer signal of a Plk1 sensor. Moreover, knockdown of Plk1 in smooth muscle attenuated force development. Smooth muscle conditional knock-out of Plk1 also diminished contraction of mouse tracheal rings. Plk1 knockdown inhibited acetylcholine-induced vimentin phosphorylation at Ser-56 without affecting myosin light chain phosphorylation. Expression of T210A Plk1 inhibited the agonist-induced vimentin phosphorylation at Ser-56 and contraction in smooth muscle. However, myosin light chain phosphorylation was not affected by T210A Plk1. Ste20-like kinase (SLK) is a serine/threonine-protein kinase that has been implicated in spindle orientation and microtubule organization during mitosis. In this study knockdown of SLK inhibited Plk1 phosphorylation at Thr-210 and activation. Finally, asthma is characterized by airway hyperresponsiveness, which largely stems from airway smooth muscle hyperreactivity. Here, smooth muscle conditional knock-out of Plk1 attenuated airway resistance and airway smooth muscle hyperreactivity in a murine model of asthma. Taken together, these findings suggest that Plk1 regulates smooth muscle contraction by modulating vimentin phosphorylation at Ser-56. Plk1 activation is regulated by SLK during contractile activation. Plk1 contributes to the pathogenesis of asthma.

Moxibustion is the main alternative medicine treatment that has been beneficial to diabetic peripheral neuropathy (DPN), a common complication secondary to diabetic microvascular injury. However, the underlying protective mechanism of moxibustion against neuroinflammation remains unclear. We hypothesized that moxibustion treats DPN by regulating the balance of nuclear factor-2 erythroid-related factor-2 (Nrf2)-nuclear factor-kappa light chain enhancer of B cells (NF-кB). In vivo, diabetes was induced in rats by injecting streptozotocin (STZ; 60 mg/kg; i.p.). Moxibustion was then applied to “Zusanli” (ST 36), “Guanyuan” (BL 26), and “Yishu” (EX-B 3) acupuncture points. Nerve conduction was detected. Serum interleukin (IL)-1β, IL-6, and IL-8 levels were determined through enzyme-linked immunosorbent assay. NF-κB and Nrf2 proteins were examined through immunoblot analysis. The mRNA of NF-κB and Nrf2 was evaluated through RT-PCR. We found that the conduction velocity and amplitude of the action potentials of sciatic nerve conduction were reduced in the DPN model group but were rescued by moxibustion treatment. Moxibustion also improved the effect of DPN on other parameters, including ultrastructural changes, NF-κB and Nrf2 expression in the sciatic nerve, and serum IL-1β, IL-6, and IL-8 levels. Our data suggested that moxibustion may alleviate neuroinflammation by inhibiting NF-κB and by activating Nrf2. Moxibustion may also provide therapeutic effects for patients with DPN by simultaneously targeting Nrf2 and NF-κB.

Background: Chronic obstructive pulmonary disease (COPD) is one of the most common lung diseases. It is a chronic inflammatory process characterised by airway obstruction and progressive lung inflammation, associated with difficulty breathing and insensitivity to corticosteroid therapy. Although there is some preliminary evidence to suggest a beneficial effect of acupuncture on COPD, its mechanism of action has not been investigated. Our aim was to examine the anti-inflammatory effects of acupuncture in a rat model of COPD induced by exposure to cigarette smoke (CS). Methods: Sixty Sprague–Dawley rats were exposed to the smoke of 15 cigarettes for 1 h/day, 6 days/week for 3 months to induce COPD and treated with acupuncture at BL13 ( Feishu), BL23 ( Shenshu) and Dingchuan (COPD+Acupuncture, n=15), sham acupuncture (COPD+Sham, n=15) or left untreated (n=15). Exposed rats were compared with controls not exposed to CS (control, n=15). Pulmonary function was measured, and tumour necrosis factor-α (TNF-α) and interleukin-8 (IL-8) levels were determined in bronchoalveolar lavage fluid by ELISA. Histone deacetylase 2 (HDAC2) protein and mRNA expression were examined in lung tissue and in bronchus. Results: Acupuncture treatment appeared to protect pulmonary function and reduce the COPD-induced inflammatory response by decreasing cell inflammation and the production of TNF-α and IL-8. Acupuncture also enhanced HDAC2 mRNA and protein expression, suggesting a possible direct effect on protein structure through post-translational modifications. Conclusions: Our results suggest that acupuncture regulates inflammatory cytokines and contributes to lung protection in a rat model of smoke-induced COPD by modulating HDAC2.

Obesity is a worldwide public health problem. Currently, increasing evidence suggests acupuncture and related therapies are effective for obesity. This network meta‐analysis (NMA) was performed to compare the effectiveness of different acupuncture and related therapies. We searched potential randomized controlled trials (RCTs) in three international databases. Thirty‐four trials involving 2283 participants were included. Pairwise meta‐analysis showed that acupuncture and related therapies were superior to lifestyle modification and placebo in reducing weight and body mass index (BMI). Based on decreases in body weight, results from NMA showed that acupoint catgut embedding (standard mean difference [SMD]: 1.26; 95% credible interval [95% CI], 0.46–2.06), acupuncture (SMD: 2.72; 95% CrI, 0.06–5.29), and combination of acupuncture and related theories (SMD: 3.65; 95% CrI, 0.96–6.94) were more effective than placebo. Another NMA result indicated that acupoint catgut embedding (SMD: 0.63; 95% CI, 0.25–1.11), acupuncture (SMD: 1.28; 95% CrI, 0.43–2.06), combination of acupuncture and related therapies (SMD: 1.44; 95% CrI, 0.64–2.38), and electroacupuncture (SMD: 0.60; 95% CrI, 0.03–1.22) were superior to lifestyle modification in decreasing BMI. Combination of acupuncture and related therapies was ranked the optimal method for both reducing weight and BMI. Further studies will clarify which combination of acupuncture and related therapies is better.

Background: Due to the effectiveness and safety, acupuncture, one of the traditional therapies of Chinese medicine, has been widely used in clinical practice globally. A few systematic review or meta-analyses have proved its effectiveness and safety towards patients with cancer pain, while there are no syntheses among those evidence. The aim of this scoping review is to summarize the evidence from systematic reviews of acupuncture for the treatment of cancer pain and evaluate the breadth and methodological quality of these evidence as well.Methods: The scoping review process was guided by the methodology framework of Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for scoping reviews (PRISMA ScR) and “Arkseyand O’Malley six-stage framework”. Electronic searches were carried out in several online databases from inception to Jan 2022. Systematic reviews and meta-analyses that involve any type of acupuncture for patients with cancer pain will be included. A pair of reviewers independently screened full texts. Moreover, review characteristics were extracted, and methodological quality was assessed using the AMSTAR 2 tool.Results: Twenty-five systematic reviews and meta-analyses were included. Manual acupuncture is the most frequently included types of test group intervention (48%), followed by acupuncture + medicine (28%), and auricular acupuncture (12%). All the reviews have declared that acupuncture is an effective method for cancer pain treatment. Eleven reviews (44%) aiming at evaluating the safety also have confirmed that acupuncture is safe for treating cancer pain. However, most included studies were conducted in China. With certain geographical limitations, the findings were not representative within the region. The results of our review may owe to the synthesis of all kinds of cancer pain, and only 2 reviews described the type of cancer pain in detail.Conclusions: This scoping review synthesizes and evaluates existing evidence of acupuncture for cancer pain. From this scoping review of systematic reviews and meta-analyses, there are clear recommendations for future studies: expanding the region of research in the world and trying to conduct the study of different types of cancer pain in details as much as possible. Evidences of acupuncture for cancer pain can inform clinical decision-making. Systematic review registration: https://inplasy.com/inplasy-2022-1-0073/, identifier INPLASY202210073.