Rhubarb granule promotes diethylnitrosamine-induced liver tumorigenesis by activating the oxidative branch of pentose phosphate pathway via G6PD in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Rhubarb is a natural herbal medicine widely used clinically with numerous pharmacological activities including anti-cancer. Specifically, several studies reported that free anthraquinones from Rhubarb suppressed the proliferation of hepatoma cells. Nonetheless, recent studies revealed that Rhubarb caused hepatotoxicity in vivo, confirming its "two-way" effect on the liver. Therefore, the efficacy and safety of Rhubarb in the in vivo treatment of liver cancer should be further elucidated. AIM OF THE STUDY: This study investigated the presence of hepatoprotection or hepatotoxicity of Rhubarb in diethylnitrosamine (DEN)-induced hepatocarcinogenesis. MATERIAL AND METHODS: A total of 112 male Sprague-Dawley rats weighing 190-250 g were enrolled. The rats were induced hepatocarcinogenesis using diethylnitrosamine (0.002 g/rat) until 17 weeks. Starting at week 11, Rhubarb granules (4 g/kg and 8 g/kg) were intragastrically administered daily for 7 weeks. All rats were euthanized at week 20 and the livers were analyzed via non-targeted metabolomics analysis. We established hepatic glucose 6 phosphate (6PG) levels and glucose 6 phosphate dehydrogenase (G6PD) activities to assess the pentose phosphate pathway (PPP). And the liver injuries of rats were analyzed via histological changes, hepatic function, as well as hepatic protein levels of alpha-fetoprotein (AFP), pyruvate kinase isozyme type M2 (PKM2), and proliferating cell nuclear antigen (PCNA). Furthermore, polydatin (0.1 g/kg/d) as a specific inhibitor of G6PD was used to treat rats. Notably, their histological changes, hepatic function, hepatic 6PG levels, hepatic G6PD activities, PCNA levels, and PKM2 levels were recorded. RESULTS: Non-targeted metabolomics revealed that Rhubarb regulated the PPP in the liver of Rhubarb-DEN-treated rats. Besides, Rhubarb activated the oxidative branch of the PPP by activating G6PD (a rate-limiting enzyme in the oxidative PPP) in the liver of Rhubarb-DEN-treated rats. Meanwhile, Rhubarb promoted DEN-induced hepatocarcinogenesis. Moreover, polydatin attenuated the promoting effect of Rhubarb on DEN-induced hepatocarcinogenesis. CONCLUSIONS: Rhubarb promoted DEN-induced hepatocarcinogenesis by activating the PPP, indicating that the efficacy and safety of Rhubarb in the treatment of liver cancer deserve to be deliberated.

A review of anti-tumour effects of ginsenoside in gastrointestinal cancer.

OBJECTIVES: Gastrointestinal cancer, one of the major causes of cancer-related deaths in the world, refers to malignant conditions of the gastrointestinal (GI) tract and other organs. Although conventional therapy has been successful to some extent in cancer treatment, drug resistance and cancer recurrence still limit the therapeutic efficacy. There is increasing evidence indicating that ginsenoside, as a kind of high nutritional value and widely used traditional Chinese medicine, could contribute to the promotion of treatment in GI cancer, which deserves further investigation. KEY FINDINGS: Based on previous studies, the possible mechanisms mainly include regulation of autophagy, apoptosis, proliferation, migration and angiogenesis. However, no studies recently have conducted a more in-depth review of the anti-cancer effects of ginsenoside in GI cancer. SUMMARY: Therefore, this review will summarise and analyse the latest developments in the anti-tumour effects of ginsenosides in GI cancer, thus may promote further research of the anti-tumour efficacy of ginsenoside.

Exosome-Based Delivery of Natural Products in Cancer Therapy.

A rapidly growing research evidence has begun to shed light on the potential application of exosome, which modulates intercellular communications. As donor cell released vesicles, exosomes could play roles as a regulator of cellular behaviors in up-taken cells, as well as a delivery carrier of drugs for targeted cells. Natural product is an invaluable drug resources and it is used widely as therapeutic agents in cancers. This review summarizes the most recent advances in exosomes as natural product delivery carriers in cancer therapy from the following aspects: composition of exosomes, biogenesis of exosomes, and its functions in cancers. The main focus is the advantages and applications of exosomes for drug delivery in cancer therapy. This review also summarizes the isolation and application of exosomes as delivery carriers of natural products in cancer therapy. The recent progress and challenges of using exosomes as drug delivery vehicles for five representative anti-cancer natural products including paclitaxel, curcumin, doxorubicin, celastrol, and ß-Elemene. Based on the discussion on the current knowledge about exosomes as delivery vehicles for drugs and natural compounds to the targeted site, this review delineates the landscape of the recent research, challenges, trends and prospects in exosomes as delivery vehicles for drugs and natural compounds for cancer treatment.

Acupuncture Relieves Stress-Induced Depressive Behavior by Reducing Oxidative Stress and Neuroapoptosis in Rats.

Oxidative stress is closely related to the occurrence of depression. Acupuncture has been proved to be an effective method for treating depression. In order to explore the mechanism of the antidepressant effect of acupuncture, this study performed acupuncture prevention on chronic unpredictable mild stress (CUMS) depression model rats, and observed the effect of acupuncture on hippocampal oxidative stress and Nrf2 signaling pathway. Male SD rats were randomly divided into control group, CUMS group, acupuncture group, and fluoxetine group (n = 10/group). Fluoxetine, a common antidepressant, was used as a positive control drug in this study. In the fluoxetine group, rats were given fluoxetine (2.1 mg/kg) intragastrically once a day for 28 days. The acupoints of Shangxing (GV23) and Fengfu (GV16) were applied in acupuncture group, once every other day for 14 times in total. Behavioral tests and biological detections were used to evaluate the effects of the interventions and the changes of factors related to oxidative stress, Nrf2 pathway, and neuronal apoptosis. The results showed that both acupuncture and fluoxetine could increase sugar preference rate in SPT and decrease immobility time in FST in depression model rats. It also significantly decreased oxidative stress products such as ROS and H2O2, and elevated the protein and mRNA expressions of Nrf2 and HO-1. From Nissl's staining, there were more abundant nerve cells in two intervention groups compared with CUMS group. Plus, acupuncture down-regulated the expression levels of Bax and caspase-3 and up-regulated the expression of Bcl-2. Our findings indicate that acupuncture improved depression-like behaviors of CUMS rats. And CUMS-induced depression-like behaviors in rats were related to oxidative stress and neuronal apoptosis in hippocampus. Acupuncture showed antidepressant effects in reducing oxidative stress products via regulating the Nrf2/HO-1 signaling pathway so that prevented neuronal apoptosis.

[Regulatory effect of Di'ao Xinxuekang on TLR4/MyD88/NF-κB signaling pathway in atherosclerotic rats].

The aim of this paper was to observe the effect of Di'ao Xinxuekang(DXXK) on TLR4/MyD88/NF-κB signaling pathway in atherosclerotic rats, and to explore its anti-atherosclerotic mechanism. Sixty SD rats were randomly divided into normal group, model group, atorvastatin group(4.0 mg·kg~(-1)), and DXXK groups(100, 30, 10 mg·kg~(-1)), with 10 rats in each group. The atherosclerosis model was induced by high fat diet plus vitamin D_2. Experimental drugs were administered intragastrically once daily for 8 weeks starting from the 9 th week. Biochemical analyzers were used to detect levels of triglyceride(TG), total cholesterol(TC), low-density lipoprotein cholesterol(LDL-C) and high-density lipoprotein cholesterol(HDL-C) in blood lipid. The levels of serum tumor necrosis factor(TNF)-α, interleukin(IL)-6 and IL-1ß were detected by ELISA. Pathological changes of aortic tissues were observed by using Sudan Ⅳ and HE staining. The mRNA and protein expressions of TLR4, MyD88 and NF-κB p65 in aortic tissues were detected by RT-PCR and Western blot, respectively. As compared with the model group, TC, TG, and LDL-C levels in serum were significantly decreased, HDL-C content was significantly increased, and levels of TNF-α, IL-6, and IL-1ß in serum were significantly decreased in atorvastatin group and DXXK high and middle dose groups. Aortic lesions in atorvastatin group and DXXK group were significantly improved, and the mRNA and protein expressions of TLR4, MyD88, NF-κB p65 in the aorta were decreased. DXXK has a preventive and therapeutic effect on atherosclerosis in rats, and its mechanism may be related to inhibiting inflammatory reaction by regulating TLR4/MyD88/NF-κB signal transduction, thereby inhibiting the progression of atherosclerosis.

[Treatment of 60 patients with temporomandibular joint dysfunction by manipulative reduction of cervical vertebrae combined with Pi needle release].

OBJECTIVE: To evaluate the clinical effects of manipulative reduction of cervical vertebrae combined with Pi needle release for the treatment of temporomandibular joint dysfunction. METHODS: From March 2012 to May 2017, 60 patients with temporomandibular joint dysfunction were treated by manipulative reduction of cervical vertebrae with Pi needle release, including 26 males and 34 females, ranging in age from 18 to 60 years old, with an average of 32.5 years old. The courses of the disease ranged from 1 week to 5 years, with a mean duration of 3 months. The patients were followed up before and after treatment by maximum active opening of temporomandibular joint, joint clicking and comparison of visual analogue scale (VAS) pain scores. RESULTS: All 60 patients were followed up, and the duration ranged from 6 to 24 months, with an average of 12 months. The maximum active opening of temporomandibular joint increased from(1.99±0.47) cm before treatment to(3.17±0.19) cm. The joint clicking decreased from 100% before treatment to(27.33±13.51)% after treatment. The VAS score decreased from 4.73±0.67 before treatment to 1.80±0.53 after treatment. CONCLUSIONS: Treatment of temporomandibular joint dysfunction by manipulative reduction of cervical vertebrae combined with Pi needle release has such advantages as easy operation, obvious curative effect, short course of treatment, which is an effective method for the treatment of temporomandibular joint dysfunction.

Treatment of 60 patients with temporomandibular joint dysfunction by manipulative reduction of cervical vertebrae combined with Pi needle release / 中国骨伤

<p><b>OBJECTIVE</b>To evaluate the clinical effects of manipulative reduction of cervical vertebrae combined with Pi needle release for the treatment of temporomandibular joint dysfunction.</p><p><b>METHODS</b>From March 2012 to May 2017, 60 patients with temporomandibular joint dysfunction were treated by manipulative reduction of cervical vertebrae with Pi needle release, including 26 males and 34 females, ranging in age from 18 to 60 years old, with an average of 32.5 years old. The courses of the disease ranged from 1 week to 5 years, with a mean duration of 3 months. The patients were followed up before and after treatment by maximum active opening of temporomandibular joint, joint clicking and comparison of visual analogue scale (VAS) pain scores.</p><p><b>RESULTS</b>All 60 patients were followed up, and the duration ranged from 6 to 24 months, with an average of 12 months. The maximum active opening of temporomandibular joint increased from(1.99±0.47) cm before treatment to(3.17±0.19) cm. The joint clicking decreased from 100% before treatment to(27.33±13.51)% after treatment. The VAS score decreased from 4.73±0.67 before treatment to 1.80±0.53 after treatment.</p><p><b>CONCLUSIONS</b>Treatment of temporomandibular joint dysfunction by manipulative reduction of cervical vertebrae combined with Pi needle release has such advantages as easy operation, obvious curative effect, short course of treatment, which is an effective method for the treatment of temporomandibular joint dysfunction.</p>

Saponins extracted from Dioscorea collettii rhizomes regulate the expression of urate transporters in chronic hyperuricemia rats.

OBJECTIVE: The current study aimed to investigate whether the saponins, bioactive component of effects of D. collettii, could reduce the serum uric acid level in a hyperuricemic mouse via regulation of urate transporters. METHODS: Chronic hyperuricemia model was established by combine administration of adenine (100mg/kg) and ethambutol (250mg/kg). In the model group, the serum uric acid (SUA), urine uric acid (UUA) volume, and 24-h UUA values increased significantly, while the uric acid clearance rate (CUr) and creatinine clearance rate (CCr) values decreased. Further, the model groups showed significantly lower expression of organic anion transporter 1 (OAT1) and organic anion transporter 3 (OAT3) and significantly higher expression of renal tubular urate transporter 1 (URAT1), glucose transporter 9 (GLUT9) and URAT1 mRNA than the normal control group. RESULTS: Saponins administration was found to have a dose-dependent effect, as evidenced by the increase in the 24-h UUA, CUr and CCr values; the decrease in SUA; the decrease in the renal expression of URAT1 mRNA and URAT1 and GLUT9 proteins; and the increase in the renal expression of the OAT1 and OAT3 proteins. CONCLUSION: The saponins extracted from D. collettii rhizomes had an obvious anti-hyperuricemic effect through downregulation of the URAT1 mRNA and the URAT1 and GLUT9 proteins and upregulation of the OAT1 and OAT3 proteins.

Mucosa-associated lymphoid tissue lymphoma with unusual 18F-FDG hypermetabolism arising at the colorectal anastomosis.

Mucosa-associated lymphoid tissue (MALT) lymphoma usually originates from the stomach and presents with low 18F-fluorodeoxyglucose (FDG) avidity with average maximum standard uptake value of 3.6. Colorectal MALT lymphoma is a rare entity that contributes to 1.6% of all MALT lymphomas and < 0.2% of large intestinal malignancies. The case reported herein firstly revealed stage IIE MALT lymphoma with unexpected higher 18F-FDG avidity of 18.9 arising at the colorectal anastomosis in a patient with a surgical history for sigmoid adenocarcinoma, which was strongly suspected as local recurrence before histopathological and immunohistochemical examinations. After accurate diagnosis, the patient received four cycles of standard R-CVP regimen (rituximab, cyclophosphamide, vincristine and prednisone), combined target therapy and chemotherapy, instead of radiotherapy recommended by National Comprehensive Cancer Network guidelines. He tolerated the treatment well and reached complete remission.

[Protective effect of Wuziyanzong Pills on rats with experimental oligoasthenospermia and its action mechanism].

OBJECTIVE: To investigate the protective effect of Wuziyanzong Pills (WYP) in the rat model of oligoasthenospermia (OAS) and its action mechanism. METHODS: Sixty male SD rats were equally randomized into six groups: normal control, OAS model, Shengjing Capsules (1.6 g per kg of the body weight), low-dose WYP (1 g per kg of the body weight), medium-dose WYP (2 g per kg of the body weight), and high-dose WYP (4 g per kg of the body weight). The OAS model was established by intragastric administration of Tripterygium glucoside at 30 mg per g per d for 6 weeks. From the 3rd week of modeling, the rats of the medication groups were treated intragastrically with corresponding drugs for 4 weeks. Then all the rats were sacrificed for measurement of the testicular and epididymal organ coefficients, examination of epididymal sperm quality and apoptosis, and detection of the openness of the sperm mitochondrial permeability transition pore (MPTP). Histopathological changes in the testis were observed by HE staining and the apoptosis of spermatogenic cells determined by Hochest staining. RESULTS: WYP obviously improved the organ coefficients of the testis and epididymis, increased sperm concentration, motility and viability, decreased the apoptosis of spermatogenic cells, and inhibited the abnormal openness of MPTP in the OAS model rats. HE staining showed that the number and levels of spermatogenic cells were significantly increased while Hochest staining manifested that the apoptosis of spermatogenic cells was remarkably inhibited in the seminiferous tubules of the testis in the WYP-treated rats. CONCLUSIONS: WYP can improve sperm quality and reduce the apoptosis of spermatogenic cells (including sperm) in OAS model rats, which may be related with its inhibitory effect on the abnormal openness of MPTP.

[Effect of total saponin of dioscorea on uric acid excretion indicators in chronic hyperuricemia rats].

OBJECTIVE: To investigate the effect of total saponin of dioscorea (TSD) on uric acid excretion indicators in chronic hyperuricemia rats, and to study the correlation between blood levels of uric acid (SUA) and uric acid excretion indicators. METHODS: Totally 90 SD male rats were randomly divided into 6 groups, i.e., the normal group, the model group, the benzbromarone group (10 mg/kg), the high, middle, and low dose TSD group (300,100, 30 mg/kg, respectively), 15 in each group. The chronic hyperuricemia model was prepared by potassium oxonate (200 mg/kg) and ethambutol (250 mg/kg) except in those of the normal group. All rats were intragastrically administered with corresponding medication once daily for 4 successive weeks since the third week. Contents of SUA and urine uric acid (UUA), serum creatinine (SCr), urine creatinine (UCr), blood urea nitrogen (BUN), and urine volume (UV) were measured on day 14 and day 28 respectively. Uric acid excretion indicators [including the amount of 24 h uric acid excretion (24 h UUA), fractional excretion of uric acid (FEUA), uric acid clearance (CUr), creatinine clearance (CCr), excretion of uric acid per volume of glomerular filtration (EurGF), and ratio of urinary uric acid to creatinine (UUA/UCr)] were calculated. The correlation between SUA and uric acid excretion indicators was analyzed by Pearson correlation analysis. RESULTS: contents of SUA and SCr significantly increased, while the UUA, 24 h UUA, CCr, CUr, FEUA, EurGF, and UUA/UCr significantly decreased in the model group on day 14 and day 28. TSD could dose-dependently reduce the SUA level, significantly increase the UUA, 24 h UUA and CCr, Cur, FEUA, EurGF, showing an approximate effect to that of benzbromarone. But it had no effect on BUN, UCr, UUA/UCr, or UV of hyperuricemia rats. Correlation analysis showed that SUA level was positively correlated with SCr on day 14 and day 28 (r = 0.359, r = 0.306), but negatively correlated with CUr, FEUA, and CCr (r = -0.749 and -0.733; r = -0.669 and -0.646; r = -0.359 and -0.273). SUA level was not correlated with EurGF or UUA/UCr (r = 0.134 and 0.078; r = -0.057 and -0. 065). SUA level was negatively correlated with 24 h UUA on day 14 (r = -0.267), but not correlated with UUA or UCr on day 14. SUA level was negatively correlated with UUA and UCr on day 28 (r = -0.269, r = -0.275), but not correlated with 24 h UUA on day 28. CONCLUSIONS: TSD could promote the excretion of uric acid and significantly increase the excretion of uric acid indicators. SUA was positively correlated with SCr, negatively correlated with Cur, FEUA, and CCr. FEUA and CUr were sensitive indicators of renal excretion of uric acid.

[Effect of total saponin of Dioscorea on chronic hyperuricemia and expression of URAT1 in rats].

OBJECTIVE: To study the preventive and therapeutic effects of total saponin of Dioscorea (TSD) on chronic hyperuricemia, and its effect on urate transporter 1 (URAT1) in rats. METHOD: Ninety male rats were randomly divided into 6 groups: the normal group, the model group, TSD high-, medium- and low-dose (300, 100, 30 mg x kg(-1)) groups and the benzbromarone (10 mg x kg(-1)) group. Potassium oxonate and ethambutol were adopted to establish the chronic hyperuricemia model Since the third week, all the rats were intragastrically administered with drugs for 4 weeks, once a day, in order to determine their uric acid in serum and urine, uric acid excretion and xanthine oxidase (XOD). URAT1 mRNA and URAT1 protein expression in rat renal tubular cells were determined by RT-PCR and immunohistochemistry method respectively. RESULT: Serum uric acid level of the model group increased significantly, while uric acid excretion decreased, with high expressions of renal URAT1 mRNA and URAT1 protein. TSD could dose-dependently reduce the serum uric acid level of chronic hyperuricemia rats, increase the concentration of uric acid and uric acid excretion in urine, and reduce renal URAT1 mRNA and URAT1 protein expression. Its effects were similar with that of benzbromarone, but with no significant effect on XOD and urinary volume of chronic hyperuricemia rats. CONCLUSION: TSD has an obvious effect of anti-hyperuricemia It may reduce the reabsorption of uric acid by inhibiting the high expression of rat renal URAT1.

[Effects of soybean isoflavones on RAGE mediated signal transduction in the hippocampus of rats with Alzheimer's disease].

OBJECTIVE: To investigate the effects of soybean isoflavones on receptor for advanced glycation end products (RAGEs) mediated signal transduction in the hippocampus of rats with Alzheimer's disease (AD). METHODS: AD rat model was established by bilateral hippocampus injection of amyloid beta25-35 (Abeta25-35). Sixty rats were equally randomized into 5 groups, i.e., the model group, the high dose soybean isoflavones group (at the daily dose of 30 mg/kg), the low dose soybean isoflavones group (at the daily dose of 10 mg/kg), the estrogen group (at the daily dose of 0.4 mg/kg), and the sham-operation control group. Three days after modeling 2 mL soybean isoflavones or estrogen was respectively administrated to rats in the high dose soybean isoflavones group, the low dose soybean isoflavones group, and the estrogen group by gastrogavage. Equal volume of 0.5% CMC-Na was administered to rats in the model group and the sham-operation group. The treatment lasted for 21 days. The contents of RAGE and interleukin-6 (IL-6) in the hippocampus were measured by ELISA. The activity of cysteine-containing aspartate-specific protease-3 (Caspase-3) was measured by spectrophotometry. The expressions of phosphorylation extracellular signal-regulated kinase1/2 (P-ERK1/2) in the hippocampus were measured by immunohistochemical assay. RESULTS: Compared with the model group, soybean isoflavones could significantly decrease the contents of RAGE and IL-6, the activity of Caspase-3, and the phosphorylation level of ERK1/2 in the hippocampus of AD model rats (P < 0.01). CONCLUSION: Soybean isoflavones could down-regulate RAGE mediated inflammatory signal transduction in the hippocampus of AD rats, attenuate the inflammatory reactions, reduce the neurotoxicity of Abeta, and resist the apoptosis of hippocampal neurons.