Hypothalamic modulation of adult hippocampal neurogenesis in mice confers activity-dependent regulation of memory and anxiety-like behavior.

Adult hippocampal neurogenesis plays a critical role in memory and emotion processing, and this process is dynamically regulated by neural circuit activity. However, it remains unknown whether manipulation of neural circuit activity can achieve sufficient neurogenic effects to modulate behavior. Here we report that chronic patterned optogenetic stimulation of supramammillary nucleus (SuM) neurons in the mouse hypothalamus robustly promotes neurogenesis at multiple stages, leading to increased production of neural stem cells and behaviorally relevant adult-born neurons (ABNs) with enhanced maturity. Functionally, selective manipulation of the activity of these SuM-promoted ABNs modulates memory retrieval and anxiety-like behaviors. Furthermore, we show that SuM neurons are highly responsive to environmental novelty (EN) and are required for EN-induced enhancement of neurogenesis. Moreover, SuM is required for ABN activity-dependent behavioral modulation under a novel environment. Our study identifies a key hypothalamic circuit that couples novelty signals to the production and maturation of ABNs, and highlights the activity-dependent contribution of circuit-modified ABNs in behavioral regulation.

Effects and safety of Tanreqing injection on viral pneumonia: A protocol for systematic review and meta-analysis.

BACKGROUND: Influenza-related viral pneumonia is a severe threat to human health, which has caused high morbidity and mortality each year. The objective of this study was to assess the efficacy and safety of Tanreqing Injection therapy in patients with viral pneumonia. MATERIALS AND METHODS: This protocol established in this study has been reported following the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols. Web of Science, PubMed, EMBASE and the Cochrane Library were searched for clinical randomized trials in cases with viral pneumonia until 1st of July 2020. We will use a combination of Medical Subject Heading and free-text terms with various synonyms to search based on the Eligibility criteria. Two investigators independently reviewed the included studies and extracted relevant data. The relative risk (RR) and 95% confidence intervals (CIs) of were used as effect estimate. I-square (I) test, substantial heterogeneity, sensitivity analysis and publication bias assessment will be performed accordingly. Stata 14.0 and Review Manger 5.3 are used for meta-analysis and systematic review. RESULTS: The results will be published in a peer-reviewed journal. CONCLUSION: The results of this review will be widely disseminated through peer-reviewed publications and conference presentations. This evidence may also provide helpful evidence of whether Tanreqing Injection therapy was efficient and safe in patients with viral pneumonia. PROSPERO REGISTRATION NUMBER: CRD42020164164.

Establishing a Cell-Based High-Content Screening Assay for TCM Compounds with Anti-Renal Fibrosis Effects.

Renal fibrosis is thought to be the final common pathway leading to chronic kidney disease (CKD) and end-stage renal failure. Except for renal replacement therapy, no adequate treatment regimen is available; therefore studies on the treatment of renal fibrosis have attracted significant interest. In recent years, studies have shown that traditional Chinese medicine (TCM) may represent an attractive source to produce drugs with antifibrosis effects. The aim of this study was to establish a robust cell-based high-content screening (HCS) approach to identify TCM compounds with antifibrosis effects in NRK49F cells following TGF-ß1 exposure. When designing the model, one of the most important steps involved the stability and reproducibility of this cell-based model. Therefore, we initially optimized the experimental parameters. Then, our HCS model was validated using SB525334, an inhibitor of the TGF-ß1 receptor, and curcumin and emodin, two TCM compounds with well-documented anti-renal fibrosis activity. Subsequently, the proven reliable HCS model was used to screen a standard TCM compound library, which included 344 TCM molecules. Based on our HCS algorithm, a total of 16 compounds were identified to have prospective inhibitory activity. These compounds were further validated by verification experiments. Strikingly, eight compounds have been shown to inhibit renal fibrosis; six of them had rarely been described in the literature, namely, Ligustrazine, Glycyrrhizic acid, Astragaloside iv, Hydroxysafflor Yellow A, Crocin, and Gypenosides. To the best of our knowledge, this is the first study in which a HCS assay was performed to identify TCM compounds with anti-renal fibrosis effects. The HCS approach was successfully applied to screen active compounds and will be propitious to further anti-renal fibrosis drugs discovery research. Meanwhile, it may offer possibilities for identifying lead compounds for treating other diseases from registered Chinese herbal medicines.

Gelsemine alleviates both neuropathic pain and sleep disturbance in partial sciatic nerve ligation mice.

AIM: Gelsemine, an alkaloid from the Chinese herb Gelsemium elegans (Gardn & Champ) Benth., is effective in mitigating chronic pain in rats. In the present study we investigated whether the alkaloid improved sleep disturbance, the most common comorbid symptoms of chronic pain, in a mouse model of neuropathic pain. METHODS: Mice were subjected to partial sciatic nerve ligation (PSNL). After the mice were injected with gelsemine or pregabalin (the positive control) intraperitoneally, mechanical allodynia and thermal hyperalgesia were assessed, and electroencephalogram (EEG)/electromyogram (EMG) recording was performed. Motor performance of the mice was assessed using rota-rod test. c-Fos expression in the brain was analyzed with immunohistochemical staining. RESULTS: In PSNL mice, gelsemine (2 and 4 mg/kg) increased the mechanical threshold for 4 h and prolonged the thermal latencies for 3 h. Furthermore, gelsemine (4 mg/kg, administered at 6:30 AM) increased non-rapid eye movement (non-REM, NREM) sleep, decreased wakefulness, but did not affect REM sleep during the first 3 h in PSNL mice. Sleep architecture analysis showed that gelsemine decreased the mean duration of wakefulness and increased the total number of episodes of NREM sleep during the first 3 h after the dosing. Gelsemine (4 mg/kg) did not impair motor coordination in PSNL mice. Immunohistochemical study showed that PSNL increased c-Fos expression in the neurons of the anterior cingulate cortex, and gelsemine (4 mg/kg) decreased c-Fos expression by 58%. Gelsemine (4 mg/kg, administered at either 6:30 AM or 8:30 PM) did not produce hypnotic effect in normal mice. Pregabalin produced similar antinociceptive and hypnotic effects, but impaired motor coordination in PSNL mice. CONCLUSION: Gelsemine is an effective agent for treatment of both neuropathic pain and sleep disturbance in PSNL mice; anterior cingulate cortex might play a role in the hypnotic effects of gelsemine.

Curcumin treatment suppresses CCR7 expression and the differentiation and migration of human circulating fibrocytes.

BACKGROUND/AIM: Recent studies have demonstrated that circulating fibrocytes contribute to the formation and development of fibrosis. Curcumin, a polyphenolic compound isolated from turmeric, has been shown to have anti-fibrotic effects in various organs. We and others have demonstrated that curcumin beneficially affects the development of fibrosis. However the effect of curcumin on circulating fibrocytes has not been reported. METHODS: Human circulating fibrocytes were isolated from leukocyte concentrates of healthy human donors and identified based on the expression of CD34, CD45, collagen I (COLI), and chemokine receptor CCR7 (CCR7) via flow cytometry. Cell Counting Kit-8 was used to evaluate cell viability. The effect of curcumin on the differentiation and migration of human circulating fibrocytes was evaluated by immunofluorescence staining, flow cytometry and a transwell migration assay. Transforming growth factor (TGF)-ß1 secretion was examined by ELISA. RESULTS: Curcumin treatment (72 h; 20 µM) significantly decreased the expression of COL I, α-SMA and CCR7, as well as TGF-ßl secretion, in human circulating fibrocytes. The inhibitory effect of curcumin on the differentiation and migration of human circulating fibrocytes is likely via regulating the CCR7/CCL21 signaling pathway, in particular by reducing CCR7 expression. These observed effects may be beneficial in resolving fibrosis by suppressing TGF-ß1 secretion. CONCLUSION: Our results suggest that curcumin has the potential to suppress the differentiation and migration of circulating fibrocytes, which would provide new explanation for curcumin's application in the development of fibrosis in various organs.

[Effects of curcumin on the epithelial mesenchymal transition and TGF-beta/Smads signaling pathway in unilateral ureteral obstruction rats].

OBJECTIVE: To observe the effects of curcumin on the epithelial mesenchymal transition (EMT) and TGF-beta/Smads signal pathway in unilateral ureteral obstruction (UUO) rats. METHODS: UUO rat model was established. Rats were divided into the sham-operation group, the model group, the 1st curcumin group, and the 2nd curcumin group, respectively. From the 2nd day after surgery, rats of the 1st curcumin group were administrated with curcumin by gastrogavage at the daily dose of 100 mg/kg. From the 10th day after surgery, rats of the 2nd curcumin group were administrated with curcumin by gastrogavage at the daily dose of 100 mg/kg. Equal volume of normal saline was given to rats by gastrogavage in the sham-operation group and the model group. On the 28th day after surgery rats were killed. The renal tissues of the obstructed side were taken out. The distribution of mice alpha-smooth muscle actin (alpha-SMA) and E-cadherin expressions were observed using immunohistochemical method. Transforming growth factor-beta 1 (TGF-beta 1), P-Smad2, P-Smad3, and Smad7 expressions were detected by Western blot. TGF-beta 1, transforming growth factor-beta receptor I (TbetaRI), collagen-I (Col-I), and collagen-III (Col-III) mRNA expressions were detected by Real-time fluorescent quantitative PCR. RESULTS: alpha-SMA expressions were obviously enhanced, E-cadherin expressions obviously weakened, the protein expression levels of P-Smad2 and P-Smad3, protein and mRNA expression levels of TGF-beta 1, TbetaRI mRNA, Col-I mRNA, and Col-III mRNA obviously up-regulated, Smad7 protein expressions obviously decreased (all P<0.01) in the renal tissues of rats in the UUO group. In the 1st curcumin group and the 2nd curcumin group, the protein expressions of alpha-SMA, P-Smad2, P-Smad3, and TGF-beta 1; mRNA expression levels of TGF-beta 1, TbetaRI mRNA, Col-I, and Col-III obviously decreased (P<0.05, P< 0.01), while the protein expressions of E-cadherin and Smad7 obviously increased (P<0.05, P<0.01). CONCLUSIONS: Curcumin could intervene several sites of the TGF-beta/Smads signal transduction pathway of UUO rats, inhibit the occurrence of EMT of renal tubular epithelial cells, thus attenuating the tubulo-interstitial fibrosis.

[Chemical principles and bioactivities of blueberry].

The bioactive principles contained in blueberries (Vaccinium) are various kind of anthocyanins (anthocyanidins, or phenolic aglycone, conjugated with sugar), chlorogenic acid, flavonids, alpha-linolenic acid, pterostilbene, resveratrol, and vitamins. After oral administration, anthocyanins can pass through blood-brain barrier and thus appear in various organs and brain. Improve visual function by increasing rhodopsin regeneration and ocular health is the earliest reported bioactivities of anthocyanin. Recent studies demonstrated the benefit of blueberries to prevent the age-related chronic diseases such as cancer, diabeties, hyperlipidemia, hypertension, neurodegeneration, obesity, and osteoporosis through its apoptosis, antioxidant, antiinflammation, and antiangiogenesis effects. Blueberries can eradicate microorganisms for the prevention of symptomatic urinary tract infections in women. Thus, blueberries are recognized as one of the most nutritious foods and cultivated worldwide. However, how to prolong the shelving time of fresh fruit, well utilize the leaf and stem to isolate the bioactive chemicals, improve quality consistency of juicy and dry products, all should be further concerned.

[Study on needling depth of Fengfu (GV 16) with CT].

OBJECTIVE: To study on needling safe depth of Fengfu (GV 16) with CT, so as to provide reference for safe needling depth of Fengfu (GV 16) in clinical acupuncture treatment. METHODS: Forty-one adult volunteers were divided into 3 groups, a thin person group, a moderate person group and a fat person group according to Luo's indexes, and computer-aided tomography (CT) was used to measure the needling depth of Fengfu (GV 16). RESULTS: The safe depths of perpendicular needling of Fengfu (GV 16) were different for persons of different somatotypes. The safe needling depth was (27.73 +/- 3.45) mm for the thin person group, (30.78 +/- 2.90) mm for the moderate person group, and (33.39 +/- 4.27) mm for the fat person group. CONCLUSION: The safe needling depth < or = the dangerous depth x 75% can be used for reference for the safe needling depth of Fengfu (GV 16) for different somatotypes persons.

[Study on needling depth of Dazhui (GV 14), Jianzhongshu (SI 15), Xuanshu (GV 5) and Mingmen (GV 4) with CT].

OBJECTIVE: To provide reference for the safe needling depth of Dazhui (GV 14), Jianzhongshu (SI 15), Xuanshu (GV 5) and Mingmen (GV 4) in clinical acupuncture and moxibustion treatment. METHODS: Thirty-two adult volunteers were divided into 3 groups, thin person group, moderate person group and fat person group according to Luo's indexes, and computer-aided tomography was used to measure the needling depth of Dazhui (GV 14), Jianzhongshu (SI 15), Xuanshu (GV 5) and Mingmen (GV 4). RESULTS: The safe depths of perpendicular needling were different for persons of different somatotypes, for example the needling depth for Dazhui (GV 14) was (32.86 +/- 3.96) mm for the thin person group, (37.76 +/- 4.91) mm for the moderate person group, and (47.93 +/- 5.30) mm for the fat person group.