Effects of moxibustion with wheat-grain size cone at "Zusanli" (ST 36) on vascular injury and oxidative stress in high-fat diet rats through mTOR/HIF-1α/VEGF signaling pathway. / 基于mTOR/HIF-1α/VEGF信号通路探讨麦粒灸"足三里"å¯¹é«˜è„‚é¥®é£Ÿå¤§é¼ è¡€ç®¡æŸä¼¤å’Œæ°§åŒ–åº”æ¿€çš„å½±å“.

OBJECTIVES: To explore the effect mechanism of moxibustion with wheat-grain size cone at "Zusanli" (ST 36) on vascular injury and oxidative stress in hyperlipidemia through mammalian target of rapamycin (mTOR)/hypoxia inducible factor-1α (HIF-1α)/vascular endothelial growth factor (VEGF) signaling pathway. METHODS: Forty healthy male SD rats with SPF grade were randomly divided into a normal group, a model group, a moxibustion group, and an inhibitor group, with 10 rats in each one. The hyperlipidemia model was established by feeding a high-fat diet for 8 weeks in rats of the model group, the moxibustion group and the inhibitor group. The moxibustion with wheat-grain size cone was delivered at bilateral "Zusanli" (ST 36) of each rat in the moxibustion group and the inhibitor group, with 3 cones on each acupoint in each intervention, once daily for 4 weeks. In the inhibitor group, before each intervention with moxibustion, rapamycin solution was injected intraperitoneally, 2.0 mg/kg. After modeling and intervention, using ELISA, the levels of total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) in the serum of rats were determined. After intervention, with HE staining and oil red O staining adopted, the abdominal aortic morphology and peripheral lipid deposition were observed. Separately, using WST-1, TBA and micro-plate method, the superoxide dismutase (SOD) activity and the levels of malondialdehyde (MDA) and nitric oxide (NO) in the serum were detected. The protein expression of mTOR, HIF-1α and VEGF in abdominal aorta were measured by Western blot method. RESULTS: Compared with those in the normal group, the levels of TC, TG and LDL-C increased (P<0.01) and HDL-C decreased (P<0.01) in the serum of the rats in the model group, the moxibustion group and the inhibitor group after model establishment. When compared with the normal group after intervention, in the model group, the serum levels of TC, TG, LDL-C and MDA increased (P<0.01), HDL-C level, SOD activity and NO level were reduced (P<0.01); the cell structure of the abdominal arota was abnormal, the peripheral lipids deposited seriously; and the protein expression of mTOR, HIF-1α and VEGF of abdominal aorta was elevated (P<0.01, P<0.05). In comparison with the model group, the levels of TC, TG, LDL-C and MDA were reduced (P<0.01), HDL-C levels, SOD activities and NO levels elevated (P<0.01, P<0.05), as well as the protein expression of mTOR, HIF-1α and VEGF of abdominal aorta (P<0.01, P<0.05) in the moxibustion group and the inhibitor group; besides, the vascular structure was ameliorated and the lipid deposition reduced in the moxibustion group, while, the vascular structure was still abnormal and the lipid deposition declined in the inhibitor group. When compared with the inhibitor group, the serum SOD activity and NO level increased (P<0.05) and MDA decreased (P<0.05); and the protein expression of mTOR, HIF-1α and VEGF of abdominal aorta was elevated (P<0.01, P<0.05) in the moxibustion group. CONCLUSIONS: The vascular injury due to hyperlipidemia is repaired by moxibustion with wheat-grain size cone at "Zusanli" (ST 36) through ameliorating oxidative stress, which is associated potentially with the modulation of mTOR/HIF-1α/VEGF signaling pathway.

Heavy metal pollution near an abandoned mercury-bearing waste recovery enterprise in southwestern China: Spatial distribution and its sources in soil and plants.

The contribution of smelting of nonferrous metals to heavy metals in surface soil have become increasingly important over the past decade. In this study, the distribution of heavy metals around an abandoned mercury-bearing waste recovery enterprise were investigated. Soil (14) and plant (18) samples were collected in the surrounding area. The total concentration of heavy metals and methyl mercury content were measured by ICP-MS and HPLC-ICP-MS. The results show that the average contents of Cd, Cr, Pb, Hg and As in all soil samples are higher than the second-level values of Soil environmental quality-Risk control standard for soil contamination of development land (GB 36600-2018). Hg in the leaves ranged from 0.003 to 0.174 mg kg-1. Besides, the Pearson correlation analysis results indicate that Hg has a different environmental behavior compared to the other heavy metal under certain environmental or geographical conditions. But the mantel test statistical analysis results show that the Cr (P < 0.01), Cu, Pb, and Fe (P < 0.05) in the soil may have similar pollution sources with carbonate-bound mercury and iron-manganese oxide-bound mercury. The Hg concentrations show no correlation among plant leaves and soil, but significantly influenced by the distance and wind direction. These findings suggest that Hg in plant leaves may be derived from the deposition of atmospheric mercury from secondary mercury plant. The results will supplement those for relevant policy making for mercury-bearing waste recovery enterprises to improve urban environmental quality and human health.

The collective vibrational modes of dihydropyridine in nifedipine studied by terahertz spectroscopy.

Cardiovascular pharmaceuticals have drawn huge attention in drug development. Nifedipine (NFD) is an important member of calcium channel blockers (CCB) with the structural characteristic of dihydropyridine (DHP), but the binding mechanism to its target remains an open question. Even though several analytical techniques have been used for structural characterizations, the information of collective vibrational behavior is still lacking. In this work, we use terahertz (THz) spectroscopy to investigate the spectral fingerprints of NFD, and quantitatively evaluate the temperature-induced frequency shifts. Combined with quantum chemical calculations, each THz fingerprint is attributed to specific collective vibrational modes. The collective vibrations of DHP are mainly distributed below 2.5 THz, which provides complementary information to understand the behavior of rigid DHP ring. The rotation of methyl group and the wagging of nitrophenyl group are widely distributed in the range of 1.0-4.0 THz, which is helpful for the conformational recognition between NFD and target molecule. THz spectroscopy is demonstrated to be suitable for characterizing the collective vibrational modes of DHP and elucidating the drug-target binding behavior from the perspective of noncovalent interactions. It has the potential to become a non-invasive technology for conformational analysis and pharmaceutical development.

Capsaicin alleviates acetaminophen-induced acute liver injury in mice.

Overdose of N-acetyl-para-aminophenol (APAP) can induce acute liver injury (ALI). We evaluated the potential protective effect of 8-methyl-N-geranyl-6-nonamide (capsaicin (CAP)) in APAP-induced ALI in mice. ALI was induced by APAP (150 mg/kg, i.p.) administration; CAP pretreatment (1 mg/kg) was undertaken before APAP injection for 3 consecutive days. We found that CAP pretreatment attenuated ALI significantly; improve the oxidative stress-associated indicators (hepatic expression of malondialdehyde (MDA) superoxide dismutase (SOD) and glutathione (GSH)); downregulate expression of proinflammatory cytokines (interleukin (IL)-6, IL-1ß, tumor necrosis factor-α) through the high-mobility group box 1/toll-like receptor-4/nuclear factor-kappa B (HMGB1/TLR4/NF-κB) signaling pathway; alleviate hepatocyte apoptosis by inhibiting expression of B-cell lymphoma-2-associated X, caspase-3 and cleaved caspase-3. CAP pretreatment reduced expression of B-cell lymphoma-2, which served as a hepatotoxic factor rather than an anti-apoptotic protein in our mouse model. We propose that CAP can alleviate APAP-induced ALI by inhibiting the inflammatory response, attenuating oxidative stress, and reducing hepatocyte apoptosis.

[Parameters and connotations of quantity of mild moxibustion stimulation].

The quantity of mild moxibustion stimulation is an important factor affecting clinical therapeutic effect. In the present study, we collected related literature by using key word "moxibustion stimulation quantity" from CNKI Database and make a summary about its concept. The quantity of mild moxibustion stimulation has two common characters, namely thermal intensity and cumulative stimulating quantity, and contains 6 components (parameters), including thermal energy, thermal stimulus, heated area of the skin, and stimulating duration, intensity and frequency. According to the facts mentioned above, we hold that the mild moxibustion quantity actually has 3 dimensions, i．e., the duration of stimulation, the stimulating quantity of one treatment session, and the total stimulating quantity of multiple treatment sessions. Accurately grasping and rationally using the basic term of the quantity of mild moxibustion is not only conductive to control clinical moxibustion operation, but also conforms to the basic requirements for quantitative control of intervention measures in experimental researches.

[Could Huatuo Jiaji (EX-B 2) Acupoint Be Assigned to the Governor Vessel ?]

The meridian tropism of acupoints is an important academic way to recognize and deal with the relationship between acupoints and meridians in acupuncture medicine. The Huatuo Jiaji (EX-B 2) (Jiaji for short) acupoint family consisting of 34 points has long been considered to be an important extra-acupoint since the ancient times of China and is widely employed in clinical practice through continuous development in Chinese past generations. The present paper introduces 1) historical origin and development of EX-B 2, and 2) intercorrelation among the EX-B 2, spine and the Governor Vessel in anatomical positions. On the basis of these, we also discuss the possibility of that EX-B 2 is assigned to the Governor Vessel, its academic significance including common features and actions in physiological and pathological aspects and clinical significance in diagnosis and treatment of disorders.

A New Type of Signaling Pathways as Pilomotor Lines along Skin for Transmitting Acupuncture Signals to Produce Acupuncture Effects.

In our previous study, we observed a linear system consisted of sympathetic endings in the arrector pili muscles (AP muscles) along the rat skin termed sympathetic substance lines, or SSLs. After shaving the hair of the rats, the first wave of hair re-growth was not evenly distributed, but followed specific hair loop lines (HLLs). The patterns of HLL and SSL correspond with each other and also with the "Meridians" described in Chinese traditional medicine (CTM). Here I investigated in rabbits and rats whether the acupuncture signals are transmitted via the SSL/HLL, and whether the acupuncture analgesia (AA) is dependent on any peripheral mechanism. Firstly, when acupuncture was operated or phenylephrine, an agonist for α receptor, was injected into the dermis at an acupoint, a pilomotor line occurred. The course of the pilomotor line coincided with the SSL/HLL. When the skin was incised or regitin, an antagonist for α receptor, was injected into the dermis, the pilomotor line did not cross the site of incision or injection. These results directly demonstrated the process of transmission of acupuncture signals involving the pilomotor line and the sympathetic. Secondly, AA produced by acupuncture at an acupoint was significantly blocked when the skin was incised or regitin was injected into the dermis along the SSL/HLL or the Meridians. [corrected]. These results suggest that the factor that blocked the pilomotor line also blocked the AA and the pilomotor line related to the AA. Lastly, noradrenaline was shown to be released from the skin along the Meridian line after acupuncture; when phenylephrine was injected into an acupoint, AA was strongly simulated. All these results indicate that: 1. the transmission pathway of acupuncture signals exists in the skin, just as the Meridians described in the CTM; 2. these pathways are the SSLs/HLLs and the pilomotor lines; and 3. the pilomotor line is just for the transmission of acupuncture signals and the transmission is dependent on the α receptor in the AP muscles, specifically the contraction of the AP muscles. Moreover, these findings suggest a new system and a new type of signal transmission in the physiology.

The existence of a linear system consisting of sympathetic endings in rat skin.

In a previous pilot study we suggested the novel notion that the catecholaminergic sympathetic nerve endings are non-homogeneously distributed in the rat skin. In the present study we have utilized several independent methods to determine the in vivo distribution of catecholamine-containing fibers in rat skin. Using whole body macro-autoradiography with an iodine125-labeled tyrosine, we localized the distribution of iodine-125-catecholamine in rat skin. The images on the film showed various pairs of symmetrical linear arrays running from the head through the back and to the hind limbs of the animal that we arbitrarily termed sympathetic substance lines (SSLs). The distribution of catecholamine in rat skin was also visualized by light microscopy autoradiography with tritiated tyrosine. The majority of silver grains in the sections were located among hair follicles along a band or zone. Furthermore, a modified sucrose-phosphate-glyoxilic acid (SPG) method was adapted to observe sympathetic fibers in the skin sections. Dense clusters of fluorescent nerve fibers in correspondence of arrector pili muscles (AP muscles) were located along lengthwise lines of the body, in a pattern coinciding with the linear arrays identified by macro-autoradiography. We concluded that concentrated clusters of noradrenergic nerve fibers innervate AP muscles and form a longitudinal linear system in the whole skin. These results are discussed in terms of physiological functions associated with hair follicles, sensory signal pathways and Meridians in Chinese traditional medicine.