Molecular Targets and Mechanisms of Hedyotis diffusa Willd. for Esophageal Adenocarcinoma Treatment Based on Network Pharmacology and Weighted Gene Co-expression Network Analysis.

BACKGROUND: Hedyotis diffusa Willd. (HDW) is a common anticancer herbal medicine in China, and its therapeutic effectiveness has been demonstrated in a range of cancer patients. There is no consensus about the therapeutic targets and molecular mechanisms of HDW, which contains many active ingredients. AIM: To clarify the mechanism of HDW for esophageal adenocarcinoma (EAC), we utilized network pharmacology and weighted gene co-expression network analysis methods (WGCNA). METHODS: The gene modules that were linked with the clinical features of EAC were obtained through the WGCNA method. Then, the potential target genes were retrieved through the network pharmacology method in order to determine the targets of the active components. After enrichment analysis, a variety of signaling pathways with significant ratios of target genes were found, including regulation of trans-synaptic signaling, neuroactive ligand-receptor interaction and modulation of chemical synaptic transmission. By means of protein-protein interaction (PPI) network analysis, we have successfully identified the hub genes, which were AR, CNR1, GRIK1, MAPK10, MAPT, PGR and PIK3R1. RESULT: Our study employed molecular docking simulations to evaluate the binding affinity of the active components with the hub gene. The identified active anticancer constituents in HDW are scopoletol, quercetin, ferulic acid, coumarin, and trans-4-methoxycinnamyl alcohol. CONCLUSION: Our findings shed light on the molecular underpinnings of HDW in the treatment of EAC and hold great promise for the identification of potential HDW compounds and biomarkers for EAC therapy.

MOXIBUSTION ALLEVIATES GASTRIC PRECANCEROUS LESIONS IN RATS BY PROMOTING CELL APOPTOSIS AND INHIBITING PROLIFERATION-RELATED ONCOGENES.

BACKGROUND: It is well known that gastric mucosa dysplasia and intestinal metaplasia are gastric precancerous lesions (GPL). Moxibustion treatment of Liangmen (ST21) and Zusanli (ST36) alleviated the inflammatory response and dysplasia of gastric mucosa in our previous study. The purpose of this study was to further examine the underlying mechanism of moxibustion treatment of ST21 and ST36 on GPL. MATERIALS AND METHODS: Sixty SD rats were divided into five groups and rats with GPL were treated with either moxibustion (ST), moxibustion (Sham), or vitacoenzyme. B-cell lymphoma 2 (bcl-2), tumor protein p53 (P53) and cellular Myc (C-MYC), which are related to cell apoptosis, proliferating cell nuclear antigen (PCNA), vascular endothelial growth factor (VEGF), argyrophilic nucleolar organizer region proteins (Ag-NORs), which are associated with cell proliferation, and cell signaling proteins, nuclear factor kappa B (NF-κB), epidermal growth factor receptor (EGFR) and phosphorylated extracellular signal regulated kinase (p-ERK), were measured after moxibustion treatment. RESULTS: Compared with Control group, gastric mucosa in GPL group showed abnormal mucosal proliferation and pathological mitotic figure, the mRNA expression of bcl-2, P53 and C-MYC increased significantly (P < 0.01), the protein expression of PCNA, VEGF, Ag-NORs and the activity of NF-κß as well as EGFR/ERK signaling proteins also increased significantly (P < 0.01). Moxibustion treatment decreased gastric mucosal proliferation and pathological mitotic figure, down-regulated the mRNA expression of bcl-2, P53, C-MYC (P < 0.01), decreased the protein expression of PCNA, VEGF, Ag-NORs and the activity of NF-κß as well as EGFR/ERK signaling proteins significantly (P < 0.01). But moxibustion treatment of Sham didn't show the same effect on GPL. CONCLUSION: Moxibustion treatment inhibited cell apoptosis and reduced gastric mucosa dysplasia by inhibiting the expression of bcl-2, P53, C-MYC and decreased the activity of NF-κß as well as EGFR/ERK signaling proteins.

[Application of "disharmony of stomach leads to insomnia" theory in acupuncture treatment for insomnia].

When looking back to the literature regarding insomnia, it is believed that "disharmony of stomach leads to insomnia" is an important mechanism for the attack of insomnia. This theory is widely accepted in clinical practices by ancient and modern acupuncturists, thus the method treating insomnia from the stomach is developed. But deeper research on its mechanism is still lacking. Through correlation between stomach meridian and heart meridian, spleen and stomach being the pivot of rise and decline of qi movement and yin-yang and being the pivot of five zang-viscera housing spirit, modern abdomen-brain theory and experimental research, the mechanism of treating insomnia from the stomach is discussed in this paper, so as to be better to guide clinical acupoint-selection and treatment.

[Effect of electroacupuncture stimulation of "Huantiao" (GB 30) on walking ability and touch sensation in rabbits with lumbar intervertebral disc protrusion].

OBJECTIVE: To observe the effect of electroacupuncture (EA) stimulation of "Huantiao" (GB 30) on the walking ability and touch sensation in rabbits with lumbar intervertebral disc protrusion (LIDP). METHODS: Forty New Zealand rabbits were equally randomized into normal control, model, EA-GB 30 and EA-non-acupoint groups. The LIDP model was established by surgical operation under anesthesia. EA (30 Hz/100 Hz, 2-4 V, 0.5 ms in pulse duration) was applied to bilateral "Huantiao" (GB 30) or non-acupoint. The rabbits' walking ability was assessed according to a 4-points scoring standard: 0 point: complete paralysis; 1 point: paralysis with muscular contraction and mild joint movement; 2 points: weaker strength of the affected limbs with bradykinesia and instable walking; 3 points: able to walk with only interphalangeal joint dyskinesia; 4 points: complete recovery. The rabbit's touch sensation was assessed according to another 4-points scoring standard: 0 point: no any response to cotton swab stimulation; 1 point: very mild response; 2 points: sluggish response; 3 points: relatively swifter response but weaker than the healthy limb; 4 points: normal. The ultrostructure changes of the sciatic nerve were analyzed by transmission electron microscope. RESULTS: Following modeling, the scores for walking ability and touch sensation were significantly reduced in the model, EA-GB 30 and EA-non-acupoint groups (P < 0.01). While compared with the model group, both walking ability score and touch sensation score of the EA-GB 30 group were obviously increased (P < 0.01), rather than in the EA-non-acupoint group. Outcomes of the ultrastructure showed that in the model group, extensive onion-like state of the myelin sheath of the sciatic nerve fibers, shrink or disappearance of the axon, kytoplasm edema or lysis of Schwann cells tending to necrosis, and mitochondrium vacuolization of the Schwann cells were found. In the EA-GB 30 group, majority of the nerve fibers and vascular endothelium were normal, with delamination and vacuolization of partial myelin sheath, edema of partial mitochondria and vacuolization of Schwann cells were found. In the EA-non-acupoint group, delamination and twist of partial myelin sheath, Schwann cellular plasma edema and mitochondrial edema of the axon with vacuolization change were found, suggesting a poorer effect of EA of non-acupoint. CONCLUSION: EA-GB 30 can improve LIDP rabbits' walking ability and touch sensation function and reduce ultrastructure of sciatic nerve.

[Regulation of moxibustion for expression of gastric mucosa cell-related marker protein in rats with acute gastric ulcer].

OBJECTIVE: To explore relevant material basis of moxibustion for recovering gastric mucosal lesion. METHODL Forty-five SD rats were randomly divided into a normal goup, a model group, an acupoint group and a control group, 15 rats in the model group and 10 rats in the rest three groups. Except the normal group, binding and cold stress method were used to establish gastric mucosa injury model. The suspended moxibustion was applied in the acupoint group and control group at acupoints of the stomach meridian ("Liangmen" (ST 21) and "Zusanli" (ST36) and control acupoints (Laterally 1cm next to the "Liangmen" (ST 21) and Zusanli" (ST36), once a day, consectutively for 12 days. After 12 days, morphology of gastric mucosal was observed under optical microscope; protein fingerprints of gastric mucosa cell in rats were detected by protein fingerprint technology, weak cation chip and weak anion chip. Also mass to charge ratio of differential proteins in groups were compared and analyzed. RESULTS: Compared with the model group, index of gastric mucosal lesion in the acupoint group was reduced and its morphology was obviously improved (P<0.05). Campared with control group, index and morphology of gastric mucosal lesion were significantly improved in the acupoint group (P<0.05). According to test of weak cation chip, there was four marker proteins that had expression differences, indicating moxibustion at acupoints of stomach meridian could inrease expression of three marker protein whose molecular weight was 1354Da, 5692Da and 8432Da (all P<0.05) while reduce expression of marker protein with molecular weight of 3287Da (_<0.05). According to test of weak anion chip, moxibustion at acupoints of stomach meridian could increase expression of three marker proteins whose molecular weight was 2412 Da, 3026Da and 6475 Da (allP<0.05). CONCLUSION: Moxibustion at acupoints of the stomach meridian could regulate differential expression of gastric mucosa cell-related marker protein in rats with acute gastric ulcer and recover gastric mucosal lesion, it's effect is better than that of the points of laterally 1 cm next to acupoint.