Stimulation of hypothalamic oxytocin neurons suppresses colorectal cancer progression in mice.

Emerging evidence suggests that the nervous system is involved in tumor development in the periphery, however, the role of the central nervous system remains largely unknown. Here, by combining genetic, chemogenetic, pharmacological, and electrophysiological approaches, we show that hypothalamic oxytocin (Oxt)-producing neurons modulate colitis-associated cancer (CAC) progression in mice. Depletion or activation of Oxt neurons could augment or suppress CAC progression. Importantly, brain treatment with celastrol, a pentacyclic triterpenoid, excites Oxt neurons and inhibits CAC progression, and this anti-tumor effect was significantly attenuated in Oxt neuron-lesioned mice. Furthermore, brain treatment with celastrol suppresses sympathetic neuronal activity in the celiac-superior mesenteric ganglion (CG-SMG), and activation of ß2 adrenergic receptor abolishes the anti-tumor effect of Oxt neuron activation or centrally administered celastrol. Taken together, these findings demonstrate that hypothalamic Oxt neurons regulate CAC progression by modulating the neuronal activity in the CG-SMG. Stimulation of Oxt neurons using chemicals, for example, celastrol, might be a novel strategy for colorectal cancer treatment.

Colorectal (or 'bowel') cancer killed nearly a million people in 2018 alone: it is, in fact, the second leading cause of cancer death globally. Lifestyle factors and inflammatory bowel conditions such as chronic colitis can heighten the risk of developing the disease. However, research has also linked to the development of colorectal tumours to stress, anxiety and depression. This 'brain-gut' connection is particularly less-well understood. One brain region of interest is the hypothalamus, an almond-sized area which helps to regulate mood and bodily processes using chemical messengers that act on various cells in the body. For instance, Oxt neurons in the hypothalamus produce the hormone oxytocin which regulates emotional and social behaviours. These cells play an important role in modulating anxiety, stress and depression. To investigate whether they could also influence the growth of colorectal tumours, Pan et al. used various approaches to manipulate the activity of Oxt neurons in mice with colitis-associated cancer. Disrupting the Oxt neurons in these animals increased anxiety-like behaviours and promoted tumour growth. Stimulating these cells, on the other hand, suppressed cancer progression. Further experiments also showed that treating the mice with celastrol, a plant extract which can act on the hypothalamus, stimulated Oxt neurons and reduced tumour growth. In particular, the compound worked by acting on a nerve structure in the abdomen which relays messages to the gut. These preliminary findings suggest that the hypothalamus and its Oxt-producing neurons may influence the progression of colorectal cancer in mice by regulating the activity of an abdominal 'hub' of the nervous system. Modulating the activity of Oxt-producing neurons could therefore be a potential avenue for treatment.

The treatment of intervertebral disc degeneration using Traditional Chinese Medicine.

ETHNOPHARMACOLOGICAL RELEVANCE: Intervertebral disc degeneration (IDD) is one of the most common causes of chronic low back pain that spending a lot of workforces and financial resources, seriously affecting human physical and mental health. Clinically used drug treatments and surgical treatments cannot fundamentally relieve the disease and have a risk of recurrence. Traditional Chinese Medicine (TCM) has a history of more than a thousand years in the prevention and treatment of IDD. However, so far, there are few reviews on the treatment of IDD by TCM. Therefore, it is crucial and necessary to systematically mine the existing literature on the treatment of IDD with TCM. This paper strives to systematically describe the modern medicine and TCM theoretical research on IDD, progress in the treatment of IDD and focuses on the treatment of IDD by TCM, which would lay some theoretical foundation and provide new directions for future research. MATERIALS AND METHODS: Information on clinical observations, animal experiments and relevant pharmacology data about the treatment of IDD were gathered from various sources including traditional Chinese books and Chinese Pharmacopoeia, scientific databases (Elsevier, PubMed, Science Direct, Baidu Scholar, CNKI, Spring Link, Web of Science) and from different professional websites. RESULTS: This review mainly introduces the current research on the theoretical research on IDD, the combination principle of the TCM formula, and the underlying mechanism of the formula and active ingredients. CONCLUSIONS: At present, domestic and foreign scholars have carried out a lot of research in different ways, such as the molecular mechanism and predisposing factors of IDD, which provides theoretical development and clinical practice significance for future research. TCM, as a multi-component and multi-targeted drug, can produce synergistic effects to exert its efficacy. Therefore, the development of TCM with more specific functions and practical data will not only become a significant trend in the world market but also has an irreplaceable role in the future treatment of IDD.

Variations of bacterial community during the decomposition of Microcystis under different temperatures and biomass.

BACKGROUND: The decomposition of Microcystis can dramatically change the physicochemical properties of freshwater ecosystems. Bacteria play an important role in decomposing organic matters and accelerating the cycling of materials within freshwater lakes. However, actions of the bacterial community are greatly influenced by temperature and the amount of organic matter available to decompose during a bloom. Therefore, it is vital to understand how different temperatures and biomass levels affect the bacterial community during the decomposition of Microcystis. RESULTS: Microcystis addition reduced the diversity of bacterial community. The composition of bacterial community differed markedly between samples with different biomass of Microcystis (no addition, low biomass addition: 0.17 g/L, and high biomass addition: 0.33 g/L). In contrast, temperature factor did not contribute much to the different bacterial community composition. Total nitrogen (TN), total phosphorus (TP), total organic carbon (TOC), ammonia nitrogen (NH4+-N) and oxidation-reduction potential (ORP) were the key measured environmental variables shaping the composition of bacterial community. CONCLUSIONS: Decomposition of Microcystis changed the physicochemical characteristics of the water and controlled the diversity and composition of the bacterial community. Microcystis biomass rather than temperature was the dominant factor affecting the diversity and composition of the bacterial community.

[Experimental study of anti-atherosclerosis potency by lycium seed oil and its possible mechanism].

OBJECTIVE: To study the effect of anti-atherosclerosis of Lycium Seed Oil (Lso) and its possible mechanism. METHODS: The rabbit atherosclerosis model was established by high fat diet, and the TC, TG, LDL-C, HDL-C levels in plasma were examined dynamically. The SOD, GSH-PX, T-AOC activities and the MDA levels in serum were monitored after 8 week's high fat diet. Aorta samples were observed for atherosclerotic extent, and NF-kappaB, TNF-alpha were assessed by immuno-histochemical method. The lovastatin was set up as a positive control. RESULTS: contents of HDL-C obviously increased in Plasma of low and high dosage groups and TC, TG, LDL-C levels significantly decreased compared with control group. The SOD, GSH-PX, T-AOC activities up-regulated while the NF-kappaB, MDA and NF-alpha levels decreased in Lycium Seed Oil groups compared with control group. Aortic atherosclerotic extent and area in low dosage and high dosage LSO groups were absolutely smaller than that in high fat diet group. The anti-atherosclerosis potency of Lycium Seed Oil was similar with that of lovastatin. CONCLUSION: Lycium Seed Oil has potent anti-atherosclerosis effects and its anti-atherosclerosis potency was similar with The lovastatin. The possible mechanism involve the decreasing of plasma lipids, anti-peroxidation, inhibiting the activation of NF-kappaB and down-regulating the inflammation cytokines of TNF-alpha.

[Antagonistic effect of 3'-daidzein sulfonate sodium on prostatic hyperplasia in mice].

OBJECTIVE: To study the antagonistic effect of 3'-daidzein sulfonate sodium (DSS) on benign prostatic hyperplasia (BPH) and its possible mechanism. METHODS: Forty healthy mice were randomly divided into five groups: a normal control group without any treatment, a model group of BPH treated by subcutaneous injection of testosterone propionate, a positive control group with the BPH procedure treated by Qianliekang, a 20 mg/(kg x d) DSS group with the BPH procedure and a 40 mg/(kg x d) DSS group with the BPH procedure. After 12 days of the above treatments, the mice were sacrificed for measurement of the prostate glandular wet weight, the index of prostate gland (PI), the morphological changes of prostate gland by light microscopy and the contents of testosterone and estradiol in the serum. RESULTS: The prostate wet weight and PI decreased dose-dependently after DSS treatment for 12 days compared with the BPH model group (P < 0.05 or P < 0.01). The hyperplastic epithelioglandular papilla waned and even disappeared in the DSS treated groups under the light microscope, the epithelial cells became cubical or flat. The effect of DSS at 40 mg/(kg x d) was similar to that of the positive anti-BPH drug Qianliekang. DSS reduced the serum testosterone, estradiol contents and the T/E2 ratio (P < 0.05 or P < 0.01). CONCLUSION: DSS has significant antagonistic effect on BPH induced by testosterone propionate in mice, which may involve its regulatory action on the sex hormone balance.

[Modified total hepatic vascular exclusion for liver extracapsular resection of giant hepatic cavernous hemangioma].

OBJECTIVE: To explore the feasibility of intraoperative autologous transfusion in modified total hepatic vascular exclusion under normal temperature for extracapsular resection of giant hepatic hemangioma. METHODS: The clinical data of 32 patients undergoing hepatic resection with total hepatic vascular exclusion requiring intraoperative autologous transfusion were analyzed retrospectively. The tumors in these cases involved the proximal hepatic veins and inferior vena cava, with hemangioma volume ranging from 12 cm x 15 cm to 18 cm x 40 cm. RESULTS: The hemangioma were completely resected in all patients, who all recovered smoothly. In one case, hemangioma rupture occurred during dissociation of the liver, resulting in massive hemorrhage which required blood transfusion of 6000 ml. Four patients received blood transfusion of 400-800 ml, and the other 27 had no blood transfusion. Only 8 patients underwent pringle maneuver with resection, whereas the other 27 underwent total hepatic vascular exclusion during liver resection for 5-30 min (mean 16 min). CONCLUSION: Intraoperative autologous transfusion in modified total hepatic vascular exclusion under normal temperature is feasible and safe for extracapsular resection of huge hepatic hemangioma adjacent to the major arteries.

Autologous transfusion with modified total hepatic vascular exclusion for extracapsular resection of giant hepatic cavernous hemangioma.

BACKGROUND: This paper was to review the effects of intraoperative autologous transfusion during modified, normal-temperature, total hepatic vascular exclusion (THVE) for extracapsular resection of giant hepatic cavernous hemangioma. METHODS: The clinical data from 28 patients, who underwent hepatic resection requiring intraoperative autologous transfusion with the cell-saver apparatus, were analyzed retrospectively. The tumors in the 28 patients involved the proximal hepatic veins and inferior vena cava. The volume of these hemangiomas ranged from 12 x 15 cm to 18 x 40 cm. All patients had varying degrees of THVE. RESULTS: The 28 patients with hemangioma received integrated resection and recovered. One patient had rupture of tumors resulting in massive hemorrhage of 6000 ml during liver resection; 4 patients had blood transfusions of 400-800 ml; the other 23 patients had no blood transfusion. Only 6 patients underwent the Pringle maneuver with resection. The other 22 patients underwent THVE during the liver resection. The interval of THVE was 5-30 minutes (mean 16 minutes). CONCLUSIONS: Intraoperative autologous transfusion during modified, normal-temperature THVE for extracapsular resection of huge hepatic cavemous hemangioma is feasible.

[Effects of xuezhikang capsules on vascular endothelial function and redox status in patients with coronary heart disease].

OBJECTIVE: To explore the effects of Xuezhikang Capsules (ZXKC) and probucol on blood lipids, vascular endothelial functions and redox status in patients with coronary heart disease. METHODS: One hundred and twelve patients with coronary heart disease were randomly divided into XZKC-treated group and probucol-treated group, 56 in each. Before and after 8-week treatment, the blood levels of total cholesterol (TC), triglycerides (TG), low density lipoprotein cholesterol (LDL-C), nitric oxide (NO), endothelin-1 (ET-1), reduced glutathione (GSH) and oxidized glutathione (GSSG) were all measured in both groups. The GSH/GSSG redox potential (Eh) was calculated according to the Nernst equation. RESULTS: In the XZKC-treated group, the blood levels of TC, LDL-C and TG were significantly decreased after 8-week treatment as compared with those before treatment. The blood levels of TC and LDL-C were also significantly decreased in the probucol-treated group as compared with those before treatment. In the XZKC-treated group, the blood levels of ET-1 and GSSG and the GSH/GSSG Eh after treatment were all significantly lower than those before treatment, whereas the blood levels of GSH and NO, the NO/ET-1 ratio, and the GSH/GSSG ratio after treatment were all significantly higher than those before treatment. CONCLUSION: The XZKC or probucol treatment can yield a significant decrease in blood lipids in patients with coronary heart disease. Furthermore, XZKC exerts effective protection on vascular endothelial function, and can make GSH/GSSG redox status shift towards deoxidation.

[Effect of triptolide on expression of urokinase-type plasminogen activators in vascular endothelial cells].

BACKGROUND & OBJECTIVE: It has been showed that triptolide (T10) has antitumor activities. This study was to observe the inhibitory effects of T10 on proliferation of vascular endothelial cells and expression of urokinase-type plasminogen activator (u-PA), and to elucidate the antiangiogenic mechanism of T10. METHODS: Human umbilical vein endothelial cells were cultured in vitro for 3 generations, and treated with T10 (0, 5, 10, 20, and 30 microg/L), or dexamethasone (300 mg/L) as control. Cell count and 3H-TDR incorporation were used to observe cell proliferation. The chick embryo chorioallantoic membrane (CAM) test was carried out to observe the effect of T10 on angiogenesis. Immunohistochemistry and real-time quantitive reverse transcription-polymerase chain reaction (RT-PCR) were used to detect protein and mRNA levels of u-PA. RESULTS: T10 inhibited the proliferation of umbilical vein endothelial cells in a dose-dependent manner; inhibitory rate of endothelial cells was 28.93% after treatment of 5 microg/L of T10. T10 significantly reduced angiogenesis in CAM, even at the concentration of 5 microg/L (P<0.05). T10 decreased protein and mRNA levels of u-PA in endothelial cells in a dose-dependent manner; the protein level of u-PA was reduced by 41.05% after treatment of 5 microg/L of T10. CONCLUSION: T10 could inhibit the proliferation of human umbilical vein endothelial cells and expression of u-PA, which may contribute to its antiangiogenic activity.