Xiaoyao San, a Chinese herbal formula, ameliorates depression-like behavior in mice through the AdipoR1/AMPK/ACC pathway in hypothalamus.

OBJECTIVE: Depression and metabolic disorders have overlapping psychosocial and pathophysiological causes. Current research is focused on the possible role of adiponectin in regulating common biological mechanisms. Xiaoyao San (XYS), a classic Chinese medicine compound, has been widely used in the treatment of depression and can alleviate metabolic disorders such as lipid or glucose metabolism disorders. However, the ability of XYS to ameliorate depression-like behavior as well as metabolic dysfunction in mice and the underlying mechanisms are unclear. METHODS: An in vivo animal model of depression was established by chronic social defeat stress (CSDS). XYS and fluoxetine were administered by gavage to the drug intervention group. Depression-like behaviors were analyzed by the social interaction test, open field test, forced swim test, and elevated plus maze test. Glucose levels were measured using the oral glucose tolerance test. The involvement of certain molecules was validated by immunofluorescence, histopathology, and Western blotting. In vitro, hypothalamic primary neurons were exposed to high glucose to induce neuronal damage, and the neuroprotective effect of XYS was evaluated by cell counting kit-8 assay. Immunofluorescence and Western blotting were used to evaluate the influences of XYS on adiponectin receptor 1 (AdipoR1), adenosine 5'-monophosphate-activated protein kinase (AMPK), acetyl-coenzyme A carboxylase (ACC) and other related proteins. RESULTS: XYS ameliorated CSDS-induced depression-like behaviors and glucose tolerance impairment in mice and increased the level of serum adiponectin. XYS also restored Nissl bodies in hypothalamic neurons in mice that exhibited depression-like behaviors and decreased the degree of neuronal morphological damage. In vivo and in vitro studies indicated that XYS increased the expression of AdipoR1 in hypothalamic neurons. CONCLUSION: Adiponectin may be a key regulator linking depression and metabolic disorders; regulation of the hypothalamic AdipoR1/AMPK/ACC pathway plays an important role in treatment of depression by XYS.

Flavonoids from Hypericum patulum enhance glucose consumption and attenuate lipid accumulation in HepG2 cells.

Hypericum patulum has been used as a folk medicine for its varied therapeutic effects including antifungal, wound-healing, spasmolytic, stimulant, hypotensive activities. The water decoction is drank as tea could treat cold, infantile malnutrition. The present study aims to isolate the constituents of the plant and investigate their effects on the glucose consumption in insulin-resistant HepG2 cells, furthermore, lipid metabolism in oleic acid (OA)-treated HepG2 cells was also studied. The phytochemical investigation of the plant led to the isolation of eleven compounds, and their structures were identified by spectroscopic analysis as n-dotriacontanol (1), shikimic acid (2), 1-O-caffeoylquinic acid methyl ester (3), 5-O-caffeoylquinic acid methyl ester (4), 5-O-coumaroylquinic acid methyl ester (5), 5-O-caffeoylquinic acid butyl ester (6), quercetin-3-O-α-L-rhamnoside (7), quercetin (8), quercetin-3-O-(4×´-methoxy)-α-L-rahmnopyranosyl (9), hyperoside (10), and rutin (11). The results revealed that compounds 7, 9, and 10 could enhance glucose consumption significantly in hyperglycemia induced HepG2 cells and insulin-resistant HepG2 cells. In addition, the western blotting analysis result exhibited that compounds 7, 9, and 10 in high concentration (5 µM, H) group could dramatically upregulate the expression of PPARγ protein, and even the effect of them had no significant difference compared with that of rosiglitazone. Furthermore, compounds 9 and 10 in middle concentration (2.5 µM, M) group and H group could dramatically promote triglyceride metabolism and decrease TG content in OA-treated HepG2 cells, and even in H group, reactive oxygen species (ROS) level were significantly decreased compared with model group. PRACTICAL APPLICATIONS: Hypericum patulum is a well-known plant of the genera Hypericum for its varied preventive and therapeutic potential activities. To study the chemical constituents and their effects on glucose and lipid metabolism in vitro, we detected glucose consumption in insulin-resistant HepG2 cells, triglyceride content and reactive oxygen species level in OA-treated HepG2 cells. In addition, PPARγ protein was also detected by western blotting analysis in the study. Compounds 1, 2, 3, 5, 6, 9, 10, and 11 were isolated from the plant for the first time. Quercetin-3-O-(4"-methoxy)-α-L-rahmnopyranosyl (9) and hyperoside (10) had potential therapeutic benefit against glucose and lipid metabolic disease. Therefore, this study might have certain guiding significance for further research and development of H. patulum.

Cervicogenic dizziness alleviation after coblation discoplasty: a retrospective study.

OBJECTIVE: Little is known about the therapeutic relationship between coblation discoplasty and cervicogenic dizziness (CGD). CGD can be caused by abnormal proprioceptive inputs from compressed nerve roots, intradiscal mechanoreceptors and nociceptors to the vestibulospinal nucleus in the degenerative cervical disc. The aim was to analyze the efficacy of coblation discoplasty in CGD through intradiscal nerve ablation and disc decompression in a 12-month follow-up retrospective study. METHODS: From 2015 to 2019, 42 CGD patients who received coblation discolplasty were recruited as the surgery group, and 22 CGD patients who rejected surgery were recruited as the conservative group. Using intent-to-treat (ITT) analysis, we retrospectively analyzed the CGD visual analogue scale (VAS), neck pain VAS, CGD frequency score, and the CGD alleviation rating throughout a 12-month follow-up period. RESULTS: Compared with conservative intervention, coblation discoplasty revealed a better recovery trend with effect sizes of 1.76, 2.15, 0.92, 0.78 and 0.81 in CGD VAS, and effect sizes of 1.32, 1.54, 0.93, 0.86 and 0.76in neck pain VAS at post-operative 1 week, and 1, 3, 6, 12 months, respectively. The lower CGD frequency score indicated fewer attacks of dizziness until postoperative 3 months (p < 0.01). At post-operative 12 months, the coblation procedure showed increased satisfactory outcomes of CGD alleviation rating (p < .001, -1.00 of effect size). CONCLUSIONS: Coblation discoplasty significantly improves the severity and frequency of CGD, which is important inbridging unresponsive conservative intervention and open surgery.Key messagesThere is a correlation between the degenerative cervical disc and cervicogenic dizziness (CGD).CGD can be caused by abnormal proprioceptive inputs from a compressed nerve root and intradiscal mechanoreceptors and nociceptors to the vestibulospinal nucleus in the degenerative cervical disc.Cervical coblation discoplasty can alleviate CGD through ablating intradiscal nerve endings and decompressing the nerve root.

Limonoids isolated from fruits of Swietenia macrophylla king enhance glucose consumption in insulin-resistant HepG2 cells via activating PPARγ.

The fruits of Swietenia macrophylla King have been processed commercially to a variety of health foods and healthcare products and exhibited antidiabetic, anti-inflammatory, antimutagenicity, antitumor activity, and so on. This study was aimed to examine the glucose consumption in human hepatoma HepG2 cells and the expression of PPARγ of limonoids isolated from the fruits of S. macrophylla. The phytochemical investigation of the fruits led to the isolation of ten limonoids which structures were elucidated by spectroscopic analysis as swietenine (1), khayasin T (2), 6-deoxyswietenine (3), 3-O-tigloylswietenolide (4), swietenolide (5), 3,6-O,O-diacetylswietenolide (6), 7-deacetoxy-7-oxogedunin (7), fissinolide (8), proceranolide (9), 7-deacetoxy-7α-hydroxygedunin (10), and compound 10 was isolated from this plant for the first time. The glucose consumption assay revealed that compounds 1, 2, 3, 5, and 9 could promote glucose consumption significantly in normal hyperglycemia-induced HepG2 cells, furthermore, compounds 1, 5, and 9 had a better effect on promoting glucose consumption in insulin-resistant HepG2 cells. In addition, compounds 1 and 5 could dramatically enhance the expression of PPARγ protein in insulin-resistant HepG2 cells according to the western blotting analysis result. PRACTICAL APPLICATIONS: Swietenia macrophylla King belongs to the family Meliaceae and the fruits have been exhibited a wide range of biological activities, such as antidiabetic, anti-inflammatory, antimutagenicity, antitumor activity, and so on. Phytochemical investigations of S. macrophylla have revealed that limonoids and triterpenoids were effective antidiabetic agents. However, the mechanism of these limonoids to antidiabetic activity is unclear. In this study, limonoids were isolated from the fruit of S. macrophylla and their effects on the glucose consumption of insulin-resistant HepG2 cells were studied. The results showed that compounds 1 and 5 could dramatically enhance the expression of PPARγ protein in insulin-resistant HepG2 cells, which will give aid to explore the mechanism of these limonoids in the treatment of type 2 diabetes. Therefore, this research might facilitate further research and development of S. macrophylla.

Computed Tomography-Guided Percutaneous Coblation of the Thoracic Nerve Root for Treatment of Postherpetic Neuralgia.

BACKGROUND: Postherpetic neuralgia (PHN) is one of the most intractable pain disorders and often does not respond to medication, physical, and interventional procedures. Coblation technology has been demonstrated to have potential for neuralgia, but there are rare reports of the efficacy and security of coblation for PHN. The thoracic segment is the most common predilection part of PHN, so we conducted this long-term study to investigate the results of coblation for the treatment of thoracic PHN. OBJECTIVES: The aim of this study was to determine the efficacy and security of computed tomography (CT)-guided coblation of the thoracic nerve root for treatment of PHN. STUDY DESIGN: Self before-after controlled clinical assessment. SETTING: Department of Pain Management, Xuanwu Hospital, Capital Medical University. METHODS: Seventy-seven patients with thoracic PHN sustained for at least 6 months and refractory to conservative therapy were identified. Patients underwent CT-guided percutaneous coblation to ablate the thoracic nerve root for thoracic PHN. The therapeutic effects were evaluated using a Visual Analog Scale (VAS), medication doses, and pain-related quality of life (QoL) scale before coblation, and at 1 week, and at 1, 3, and 6 months after the procedure. Patients who achieved more than 50% pain relief were defined as responders. In addition, adverse effects were also recorded to investigate the security of this procedure. RESULTS: The VAS score significantly decreased from 7.22 ± 1.15 before the coblation to 3.51 ± 1.12 (P = 0.01), 3.02 ± 1.21 (P = 0.006), 3.11 ± 2.15 (P = 0.014), and 2.98 ± 2.35 (P = 0.008) at 1 week, and at 1, 3, and 6 months after the procedure, respectively. The number of responders were 56 (77.78%), 54 (75%), 55 (76.39%), and 54 (75%) at 1 week, and at 1, 3, and 6 months after the procedure, respectively. The doses of anticonvulsants and analgesics were decreased significantly at all time points after the procedure compared with before treatment (P < 0.05). Patient responses on the Brief Pain Inventory Short Form indicated mean scores that were significantly lower than baseline across all domains of pain interference with QoL at all evaluations (P = 0.001). Most of the patients had mild numbness and it did not affect the daily activities after the procedure. No other severe adverse events occurred during or after the procedure. LIMITATIONS: A single-center study, relatively small number of patients, short duration of review of medical record, and the retrospective study. CONCLUSIONS: CT-guided percutaneous thoracic nerve root coblation is an effective and safe method for the treatment of thoracic PHN, and the procedure can also significantly improve the QoL in patients with PHN.

Translationally-controlled tumor protein activates the transcription of Oct-4 in kidney-derived stem cells.

The molecular mechanisms underlying translationally-controlled tumor protein (TCTP) in the activation of octamer-binding transcription factor 4 (Oct-4) in kidney-derived stem cells have not been characterized. The aim of the present study was to identify the transcriptional activation of Oct-4 by TCTP in kidney-derived stem cells. Homology-directed repair cDNA inserted into Fisher 344 transgenic (Tg) rats and the mouse strain 129/Svj were used for the experiments. Diphtheria toxin (DT; 10 ng/kg) injected into the Tg rats created the kidney injury, which was rapidly restored by the activation of kidney-derived stem cells. Kidney-derived stem cells were isolated from the DT-injured Tg rats using cell culture techniques. The co-expression of Oct-4 and TCTP were observed in the isolated kidney-derived stem cells. Immunoblotting and reverse transcription-polymerase chain reaction analysis of TCTP null mutant (TCTP-/-) embryos at day 9.5 (E9.5) demonstrated the absence of co-expression of Oct-4 and TCTP, but expression of paired box-2 was detected. This was in contrast with the E9.5 control embryos, which expressed all three proteins. In conclusion, the results of the present study demonstrated that TCTP activates the transcription of Oct-4 in kidney-derived stem cells, as TCTP-/- embryos exhibited knock down of TCTP and Oct-4 without disturbing the expression of Pax-2 The characteristics and functional nature of TCTP in association with Oct-4 in kidney-derived stem cells was identified.

Trigeminal somatosensory-evoked potential: A neurophysiological tool to monitor the extent of lesion of ganglion radiofrequency thermocoagulation in idiopathic trigeminal neuralgia: A case-control study.

To reflect the extent of thermolesion of ganglion by testing the change of trigeminal somatosensory-evoked potential (TSEP) before and after ganglion radiofrequency thermocoagulation surgery (GRT), and evaluate long-term clinic effect by follow-up visiting of 1 year.Patients with idiopathic trigeminal neuralgia (TN) in the second division were enrolled between October 2014 and October 2015. They were treated with computed tomography-guided GRT and a follow-up visiting of 1 year. Bilateral TSEP measurements were performed 1 day before and 2 days after the GRT surgery. The latency and peak-to-peak amplitude of W2 and W3 were recorded.Immediate postprocedure pain relief (grades I-III) was 100% and 92.5% 1 year later. Facial numbness rate of grades III and IV was 70%, 40%, and 12.5%, respectively, at immediate, 2 days, and 1 year after GRT. No sever complications happened. The latency of W2 and W3 of patients who had no pain no numbness after 1 year of GRT was 1.74 ±â€Š0.24 and 3.84 ±â€Š0.66 ms, respectively, of TN side, and 1.71 ±â€Š0.39 and 3.63 ±â€Š0.85 ms of the healthy side before GRT. The amplitude of W2 and W3 was 1.13 ±â€Š0.50 and 1.99 ±â€Š1.09 uv, respectively, of TN side and 1.24 ±â€Š0.40 and 1.89 ±â€Š0.81 uv of the healthy side before GRT. There was no statistical difference of the latency and amplitude between 2 sides of W2 and W3 before surgery (P > 0.05). The latency of W2 and W3 delayed and the amplitude reduced especially in TN side after surgery comparing before (P < 0.001). And, comparisons of the latency and amplitude of W2 and W3 between TN side and the healthy side after surgery showed the latency of W2 and W3 delayed (W2: P = 0.02; W3: P = 0.01) and the amplitude of W2 reduced (P = 0.003), but the amplitude of W3 had no statistical difference (P = 0.22). The mean delayed latency and 95% confident interval of W2 and W3 were 0.22 ±â€Š0.35 (0.1-0.34) ms and 0.35 ±â€Š0.64 (0.14-0.57) ms, respectively. The mean decreased amplitude and 95% confident interval of W2 and W3 were 22 ±â€Š24 (14-30)% and 23 ±â€Š32 (12-34)%, respectively.GRT can make the latency delay and the amplitude decrease of TSEP. And the latency and amplitude of W2 and W3 can be considered reliable and safe reference for monitoring the extent of thermolesion.

Involvement of the Hippo pathway in regeneration and fibrogenesis after ischaemic acute kidney injury: YAP is the key effector.

Renal tubule cells can recover after they undergo AKI (acute kidney injury). An incomplete repair of renal tubules can result in progressive fibrotic CKD (chronic kidney disease). Studies have revealed the relationship between tubular epithelial cells and kidney fibrogenesis. However, the underlying mechanism remains unclear. Hippo pathway components were evaluated in complete/incomplete repair of I/R (ischaemia/reperfusion) AKI rat models, HK-2 cells and AKI human renal biopsy samples. We found that the expression levels of the Hippo pathway components changed dynamically during kidney regeneration and fibrogenesis in rat models of I/R-induced AKI and human renal biopsy samples. The transcription cofactor YAP (Yes-associated protein) might be a key effector of renal regeneration and fibrogenesis. Our results showed further that YAP might elicit both beneficial and detrimental effects on I/R AKI. After I/R injury occurred, YAP could promote the repair of the injured epithelia. The constant YAP increase and activation might be related to interstitial fibrosis and abnormal renal tubule differentiation. These results indicate that the proper modulation of the Hippo pathway, specifically the transcription cofactor YAP, during repair might be a potent therapeutic target in AKI-CKD transition after I/R injury.