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The non-small-cell lung cancer (NSCLC) is the most common lung cancer which seriously threatens the human health. Xu Li's experiential prescription (XLEP) can treat the NSCLC. However, whether XLEP can regulate the autophagy in the EGFR-positive NSCLC still remains unknown. We found that the cellular activity of drug-resistant cells and sensitive cells were all decreased in the TCM group and TCM + Gef group. The expression of autophagy-associated proteins (mTOR and Beclin1-Vps34) in drug-resistant cells was decreased in the TCM group, while the expression of autophagy-associated proteins in sensitive cells was all decreased in the TCM + Gef group. The ratio of M1/M2 macrophages was increased when IL-4-induced RAW264.7 was treated with TCM. TCM treatment promoted the expression of CCL2 and CCL3 while it downregulated the CCL22 level among A549, H1975, and PC9 cells. The expression of TNF-α and IL-6 was increased, and the expression of IL-10 and TGF-β was decreased in IL-4-induced RAW264.7 cells treated with TCM. And, TCM treatment also decreased the expression of Fizz1 and TGM2. In conclusion, this study indicated that XLEP could suppress the proliferation of EGFR-TKI-resistant cancer cells and increase the ratio of M1/M2 macrophages by inhibiting autophagy to treat the drug-resistant EGFR-positive NSCLC. [ABSTRACT FROM AUTHOR]

Background. Jinlian Xiaodu Decoction (JXD) was reported to have anti-inflammatory and lung protection effects. This study aimed to explore the role and mechanism of JXD on bleomycin (BLM)-induced pulmonary fibrosis (PF). Methods. The UHPLC-Q/TOF-MS system was applied to analyze JXD composition. The PF model was established by BLM intratracheal administration in Wistar rats. Subsequently, BLM-treated rats were intragastrically administered with dexamethasone (DXM, 1 g/kg/d) or JXD (3.5, 7 or 14 g/kg/d). Next, the lung coefficient was calculated; H&E, Masson, and TUNEL staining were used for lung morphological analysis and apoptosis assessment. Bronchoalveolar lavage fluid (BALF) biochemical analysis was conducted to count the inflammatory cell number. The expression of inflammatory factors mRNA in the lung tissue and BALF were measured by qRT-PCR. The content and activity of oxidative stress-related proteins were detected. The expression of PF-related, apoptosis-related, and TGF-β1 pathway-related protein were assessed by immunohistochemistry or Western blot. Results. Twenty-six compounds were identified from JXD in both negative and positive ion modes. In BLM-induced rats, JXD reduced the lung coefficient and alleviated PF injury. JXD decreased inflammatory cell count and TNF-α, IL-1β, IL-6, and MCP-1 content. Meanwhile, JXD blunted BLM-induced oxidative stress and a high level of HYP. Furthermore, TUNEL analysis found that JXD inhibited cell apoptosis and increased Bcl-2/Bax ratio in BLM-induced lung. Moreover, JXD relieved the role of BLM on α-SMA, TGF-β1, collagen I, fibronectin, E-cadherin protein expression, and the phosphorylation of Smad2/3 in PF rat. Conclusion. This study revealed the protective effect and possible element of JXD on BLM-caused PF. [ABSTRACT FROM AUTHOR]

Acupuncture can significantly ameliorate inflammatory pain in acute visceral hyperalgesia. Hyperalgesia is attenuated by inflammatory mediators that activate transient receptor potential vanilloid 1 (TRPV1), and TRPV1 is regulated by nerve growth factor (NGF)-induced phosphatidylinositol 3-kinase (PI3K)/Akt pathway. However, it is unknown whether NGF-induced PI3K/Akt pathway is associated with manual acupuncture (MA). In this study, the effect and mechanism of MA at Shangjuxu (ST37) and Quchi (LI11) were examined using an acetic acid-induced rat model with visceral hyperalgesia. We demonstrated that MA at ST37 significantly decreased abdominal withdrawal reflex (AWR) scores, proinflammatory cytokine expression (TNF-α, IL-1β, and IL-6), and TRPV1 protein and mRNA expression in rats with acute visceral hyperalgesia compared with the untreated controls, while MA at LI11 showed no effect. The effects of MA at ST37 were reversed after treatment with the PI3K agonist IGF-1 30 min before MA. In rats with visceral hyperalgesia, the upregulation of NGF, tropomyosin-receptor-kinase A (TrkA), PI3K, and phosphorylation-Akt (p-Akt) was decreased by MA at ST37, indicating that TRPV1 regulation via the NGF-induced PI3K/Akt pathway plays a vital role in the effects of MA-mediated amelioration of acute visceral hyperalgesia. [ABSTRACT FROM AUTHOR]

Electroacupuncture (EA) can effectively relieve hyperglycemia and gastric emptying disorders in diabetic gastroparesis (DGP). However, the effect of EA on type 2 diabetes mellitus (T2DM) gastroparesis and its mechanism in the enteric nervous system (ENS) are rarely studied. We investigated the therapeutic effect of EA at ST36 and its effect on the main inhibitory and excitatory neurotransmitters in the ENS in DGP rats. Male Sprague-Dawley (SD) rats were fed a high-fat diet for 2 weeks and injected with streptozotocin (STZ) at 35 mg/kg to induce T2DM. T2DM rats were divided into the diabetic mellitus (DM) group and the EA group. The control (CON) group comprised normal rats without any intervention. EA treatment was started 6 weeks after the induction of DM and continued for 5 weeks. The body weight and food intake of the rats were recorded every week. Blood glucose, insulin, glucose tolerance, gastric emptying, and antral motility were measured after treatment. The expression of protein gene product 9.5 (PGP9.5), neuronal nitric oxide synthase (nNOS), and choline acetyltransferase (ChAT) in gastric antrum were quantified by western blotting and quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR). The T2DM gastroparesis model was successfully established. EA treatment reduced the body weight, food intake, and blood glucose; improved glucose intolerance and insulin resistance; increased the gastric emptying rate, the mean antral pressure, and the amplitude of antral motility; and decreased the frequency of antral motility compared with those in the DM group. EA treatment increased the expression level of nNOS, ChAT, and PGP9.5 proteins, and nNOS and ChAT mRNA. The results suggested that EA at ST36 could ameliorate DGP, partly restore the damage to general neurons, and increase nNOS and ChAT in the gastric antrum. EA improved DGP partly via reducing the loss of inhibitory and excitatory neurotransmitters in the ENS. [ABSTRACT FROM AUTHOR]

A thin endometrium affects the success of assisted reproduction due to low endometrial receptivity. Acupuncture improves endometrial receptivity and promotes the formation of pinopodes, the ultrastructure marker implantation window. However, the specific underlying mechanisms remain unclear. In this study, the efficacy of acupuncture treatment and its underlying mechanism were investigated by analyzing pregnancy rate, pinopode formation, and related molecular markers in thin endometrium model rats. Absolute ethanol (95%) was injected into the uteruses of female Sprague-Dawley rats to construct a thin endometrium model. In this model, acupuncture stimulation at EX-CA1, SP6, and CV4 ameliorated the pregnancy rate. Significantly increased embryo implantation, endometrial thickness, numbers of glands, and blood vessels were observed in the electroacupuncture (EA) group compared to the model group. The number of pinopodes in the EA group was abundant, with a shape similar to that of the control group. Additionally, significantly higher expression levels of pinopode-related markers, including integrin αvβ3, homeobox A10 (HOXA10), heparin-binding EGF-like growth factor (HBEGF), estrogen receptor alpha (ERα), and progesterone receptor (PR), were observed in the EA group than those in the model group. In conclusion, EA had a positive effect on the endometrial receptivity of thin endometrium model rats by improving pinopode formation through multiple molecular targets. [ABSTRACT FROM AUTHOR]

Background. Osteonecrosis of the femoral head (ONFH) is a challenge for surgeons and is still without effective treatment method. This study is aimed at evaluating the combined pharmacotherapy with alendronate and desferoxamine for preventing glucocorticoid-induced osteonecrosis of the femoral head (GIOFH) and evaluating the efficacy of the combined medicine in regulating the bone resorption and bone regeneration. Materials and Methods. Thirty-six rats were randomly assigned to three groups: group A received alendronate and desferoxamine (n = 12), group B received alendronate only (n = 12), and group C acted as the control group received placebo (n = 12). All rats induced the GIOFH using methylprednisolone combined with lipopolysaccharide. Eight weeks later, all rats were killed and their tissues were subjected to radiographic and histological analyses. Results. According to the results, alendronate administration improved the trabecular thickness and separation in micro-CT analysis but had no significant evidence in increasing the bone area and decreasing the ratio of osteocyte lacunae in histological analysis when compared with the control group. Meanwhile, the alendronate group had more OCs, but less OCN and VEGF levels along with decreased p-AKT, HIF-1α, RANKL, and NFATc1 expressions than the control group. For comparison, alendronate combined with DFO further improved the bone volume, trabecular number, trabecular separation, and trabecular thickness with lower ratio of osteocyte lacunae and OC number, higher expression of OCN and VEGF and upregulated signal factors of HIF-1α and β-catenin, and decreased RANKL and NFATc1. Conclusion. Combined pharmacotherapy with alendronate and desferoxamine provide significant effects in regulating the bone resorption and bone regeneration for preventing GIOFN. [ABSTRACT FROM AUTHOR]

Background. We aimed to assess whether electroacupuncture (EA) at PC6 affects gastric motility via the vagovagal reflex and if so whether brainstem vagovagal neurocircuits and related transmitters are involved. Methods. Gastric motility was measured in male Sprague-Dawley (SD) rats by placing a small manometric balloon in the gastric antrum. The rats were subjected to control, sham surgery, vagotomy, sympathectomy, and microinjection group, including artificial cerebrospinal fluid, gamma-aminobutyric acid (GABA), and glutamic acid (L-Glu). The effect of EA at PC6 on gastric motility was measured. Moreover, electrophysiological testing was used to measure the effect of EA at PC6 on the parasympathetic and sympathetic nerves. In addition, artificial cerebrospinal fluid, L-Glu, and GABA have been microinjected into the dorsal motor nucleus of the vagus (DMV) to measure the changes in gastric motility and parasympathetic nerve discharge induced by EA at PC6. Key Results. EA facilitated the gastric motility in control group. In the vagotomy group, gastric motility was not affected by EA at PC6. However, in the sympathectomy group, gastric motility was similar to control group. Acupuncture at PC6 increased parasympathetic nerve discharge but not sympathetic nerve discharge. Furthermore, the microinjection of L-Glu into the DMV increased gastric motility, although EA at PC6 showed no remarkable change in this group. The injection of GABA reduced gastric motility and parasympathetic nerve discharge, but EA at PC6 significantly increased gastric motility and the parasympathetic nerve discharge in this group. Conclusions and Inferences. EA at PC6—primarily by inhibiting GABA transmission to DMV—reduced the inhibition of efferent vagal motor fibers and thus promoted efferent vagus nerve activity and increased gastric motility. [ABSTRACT FROM AUTHOR]

Background. The roles of the sympathetic and parasympathetic systems in mediating the effect of electroacupuncture (EA) at ST37 on jejunal motility have yet to be demonstrated. Aim. We used rats and mice to investigate the effect and mechanism of action of EA at ST37 on jejunal motility. Methods. Jejunal motility was recorded by a balloon placed in the jejunum and connected to a biological signal collection system through a transducer. The effects of EA (3 mA) at ST37 were evaluated in Sprague-Dawley rats without drugs and with the administration of clenbuterol, propranolol, acetylcholine, and atropine. Further, the efficacy of EA at different intensities (1/2/4/6/8 mA) was measured in wild-type mice and β1β2-/- mice and M2M3-/- mice. Results. In Sprague-Dawley rats, the excitatory effect of EA at ST37 on jejunal motility disappeared in the presence of the muscarinic receptor antagonist atropine. EA at ST37 was less effective in M2M3-/- mice than in wild-type mice. Furthermore, to a certain extent, there existed “intensity-response” relationship between jejunal motility and EA. Conclusions. EA at ST37 can enhance jejunal motility in rats and mice mainly via excitation of the parasympathetic pathway. There is an “intensity-response” relationship between EA and effect on jejunal motility. [ABSTRACT FROM AUTHOR]

Background. Previous studies have demonstrated the efficacy of frequency-specific EAS. However, evaluation of intensity-response effects is challenging and has yet to be addressed. Aims. Using cisapride to promote gastric emptying, we measured the intensity-response relationship of EA at ST25 on gastric motility. Methods. We determined the effects of EA at ST25 using intensities (0.5, 1, 3, 5, 7, and 9 mA) on gastric motility in rats injected with cisapride (0.2, 0.02, and 0.002 mg/kg). Results. Utilizing three concentrations of cisapride yielded significantly differing levels of gastric motility. Furthermore, log IC50 values for EAS were different within each group. Given the same EA intensity, cisapride antagonism decreased progressively in each group as a function of drug concentration. The relative amount of cisapride antagonized by EAS did not change in a linear fashion. Finally, EAS at different intensities within the three groups induced a similar pattern of cisapride antagonism. Conclusions. The ability of EAS to elicit a decrease in cisapride-induced gastric motility pressure was demonstrated in this study. The study encompasses construct validity to mirror individualized treatment being based on patients’ subjective feelings, not on a set fixed EA intensity. Clinically utilizing EAS at the smallest intensity can achieve the desired therapeutic effect. [ABSTRACT FROM AUTHOR]