Tribuloside acts on the PDE/cAMP/PKA pathway to enhance melanogenesis, melanocyte dendricity and melanosome transport.

ETHNOPHARMACOLOGICAL RELEVANCE: Tribuloside, a natural flavonoid extracted from Chinese medicine Tribulus terrestris L., has shown potent efficacy in treating various diseases. In China, the fruits of Tribulus terrestris L. have long been utilized for relieving headache, dizziness, itchiness, and vitiligo. Water-based extract derived from Tribulus terrestris L. can enhance melanogenesis in mouse hair follicle melanocytes by elevating the expression of α-melanocyte stimulating hormone (α-MSH) and melanocortin-1 recepter (MC-1R). Nevertheless, there is a lack of information regarding the impact of tribuloside on pigmentation in both laboratory settings and living organisms. AIM OF THE STUDY: The present research aimed to examine the impact of tribuloside on pigmentation, and delve into the underlying mechanism. MATERIALS AND METHODS: Following the administration of tribuloside in human epidermal melanocytes (HEMCs), we utilized microplate reader, Masson-Fontana ammoniacal silver stain, transmission electron microscopy (TEM) and scanning electron microscopy (SEM) to measure melanin contents, dendrite lengths, melanosome counts; L-DOPA oxidation assay to indicate tyrosinase activity, Western blotting to evaluate the expression of melanogenic and associated phosphodiesterase (PDE)/cyclic adenosine monophosphate (cAMP)/cyclic-AMP dependent protein kinase A (PKA) pathway proteins. A PDE-Glo assay to verify the inhibitory effect of tribuloside on PDE was also conducted. Additionally, we examined the impact of tribuloside on the pigmentation in both zebrafish model and human skin samples. RESULTS: Tribuloside had a notable impact on the production of melanin in melanocytes, zebrafish, and human skin samples. These functions might be attributed to the inhibitory effect of tribuloside on PDE, which could increase the intracellular level of cAMP to stimulate the phosphorylation of cAMP-response element binding (CREB). Once activated, it induced microphthalmia-associated transcription factor (MITF) expression and increased the expression of tyrosinase, Rab27a and cell division cycle protein 42 (Cdc42), ultimately facilitating melanogenesis, melanocyte dendricity, and melanin transport. CONCLUSION: Tribuloside acts on the PDE/cAMP/PKA pathway to enhance melanogenesis, melanocyte dendricity, and melanosome transport; meanwhile, tribuloside does not have any toxic effects on cells and may be introduced into clinical prescriptions to promote pigmentation.

[Role of TGF-ß/Smad signaling pathway in diabetic kidney disease and research progress of traditional Chinese medicine intervention].

Diabetic kidney disease is an important microvascular complication of diabetes and the leading cause of end-stage renal disease. Its pathological characteristics mainly include epithelial mesenchymal transition(EMT) in glomerulus, podocyte apoptosis and autophagy, and damage of glomerular filtration barrier. Transforming growth factor-ß(TGF-ß)/Smad signaling pathway is specifically regulated by a variety of mechanisms, and is a classic pathway involved in physiological activities such as apoptosis, proliferation and differentiation. At present, many studies have found that TGF-ß/Smad signaling pathway plays a key role in the pathogenesis of diabetic kidney disease. Traditional Chinese medicine has significant advantages in the treatment of diabetic kidney disease for its multi-component, multi-target and multi-pathway characteristics, and some traditional Chinese medicine extracts, traditional Chinese medicines and traditional Chinese medicine compound prescription improve the renal injury of diabetic kidney disease by regulating TGF-ß/Smad signaling pathway. This study clarified the mechanism of TGF-ß/Smad signaling pathway in diabetic kidney disease by expounding the relationship between the key targets of the pathway and diabetic kidney disease, and summarized the research progress of traditional Chinese medicine in the treatment of diabetic kidney disease by interfering with TGF-ß/Smad signaling pathway in recent years, to provide reference for drug research and clinical treatment of diabetic kidney disease in the future.

Intestinal activating transcription factor 4 regulates stress-related behavioral alterations via paraventricular thalamus in male mice.

Chronic stress induces depression- and anxiety-related behaviors, which are common mental disorders accompanied not only by dysfunction of the brain but also of the intestine. Activating transcription factor 4 (ATF4) is a stress-induced gene, and we previously show that it is important for gut functions; however, the contribution of the intestinal ATF4 to stress-related behaviors is not known. Here, we show that chronic stress inhibits the expression of ATF4 in gut epithelial cells. ATF4 overexpression in the colon relieves stress-related behavioral alterations in male mice, as measured by open-field test, elevated plus-maze test, and tail suspension test, whereas intestine-specific ATF4 knockout induces stress-related behavioral alterations in male mice. Furthermore, glutamatergic neurons are inhibited in the paraventricular thalamus (PVT) of two strains of intestinal ATF4-deficient mice, and selective activation of these neurons alleviates stress-related behavioral alterations in intestinal ATF4-deficient mice. The highly expressed gut-secreted peptide trefoil factor 3 (TFF3) is chosen from RNA-Seq data from ATF4 deletion mice and demonstrated decreased in gut epithelial cells, which is directly regulated by ATF4. Injection of TFF3 reverses stress-related behaviors in ATF4 knockout mice, and the beneficial effects of TFF3 are blocked by inhibiting PVT glutamatergic neurons using DREADDs. In summary, this study demonstrates the function of ATF4 in the gut-brain regulation of stress-related behavioral alterations, via TFF3 modulating PVT neural activity. This research provides evidence of gut signals regulating stress-related behavioral alterations and identifies possible drug targets for the treatment of stress-related behavioral disorders.

Three Acupuncture Methods for Postoperative Pain in Mixed Hemorrhoids: A Systematic Review and Network Meta-Analysis.

Background: Mixed hemorrhoids are a common anorectal disorder, surgery is the most effective means of eradicating hemorrhoids, and pain is the most common postoperative complication of mixed hemorrhoids. Objective: To compare the clinical efficacy of auricular plaster, acupoint application, and acupoint catgut embedding for treating postoperative pain in mixed hemorrhoids. Method: PubMed, Embase, The Cochrane Library, Web of Science, CNKI, Wanfang, VIP, and CBM databases were searched for randomized controlled trials (RCTs) of three acupuncture-related therapies for postoperative pain in mixed hemorrhoids from the time of database creation to October 2021. After screening the literature, extracting information, and evaluating the risk of bias of included studies, statistical analysis was performed using RevMan 5.3 and Stata 15.0. Result: Forty-seven RCTs with a total of 5121 patients were included. Network meta-analysis (NMA) showed that auricular plaster (OR = 5.90, 95% CI = (2.02, 17.21)) and acupoint catgut embedding therapy (OR = 5.55, 95% CI = (1.01, 30.40)) were more effective than analgesics in the treatment of postoperative pain in mixed hemorrhoids. The cumulative ranking probability (SUCRA) showed that acupoint application (73.6%) had the best overall efficacy and the rest were auricular plaster (68.7%), acupoint catgut embedding therapy (64.6%), auricular plaster combined with acupoint application (63.4%), and pain medication (8.9%) in that order. Secondly, auricular plaster (OR = -0.93, 95% CI = (-1.66, -0.20)), acupoint catgut embedding (OR = -0.8, 95% CI = (-1.50, -0.10)), and acupoint application (OR = -1.4, 95% CI = (-2.50, -0.31)) all led to a significant decrease in pain scores and were all more effective than analgesics. As ranked by SUCRA, the results showed that the efficacy of acupoint application (73.5%) was optimal and the rest were auricular plaster (56.1%), acupoint catgut embedding (50.2%), and pain medication (15.3%) in that order. In terms of pain degree, acupoint application (OR = 3.83, 95% CI = (1.25, 11.74)) was significantly better than pain medication. Conclusion: Acupoint application can improve the overall efficiency, reduce pain scores, and relieve the degree of postoperative pain in mixed hemorrhoids.

Acupuncture and Moxibustion in the Treatment of Adult Diarrhea Irritable Bowel Syndrome: A Network Meta-analysis.

Objective: This study was aimed at comparing the clinical efficacy of acupuncture and moxibustion on irritable bowel syndrome complicated with diarrhea (IBS-D) in adults and providing guidance for clinical treatment. Methods: PubMed, The Cochrane Library, Embase, CBM, CNKI, and VIP and Wanfang databases were searched to obtain clinical randomized controlled trials (RCTs) on acupuncture and moxibustion in the treatment of IBS-D published from establishment of the database to August 5, 2021. Relevant data were extracted to assess the risk of bias in the included studies, and statistical software Stata 16.0 was used for meta-analysis. Results: Twenty-one studies were eventually included in the network meta-analysis (NMA), including 1626 patients with IBS-D and 8 therapeutic measures. NMA showed that acupuncture [OR = 0.35, 95%CI (0.25, 0.49), P < 0.05], warming needle moxibustion [OR = 6.34, 95%CI (2.83, 14.21), P < 0.05], acupuncture+sandwiched moxibustion [OR = 12.83, 95%CI (4.49, 36.64), P < 0.05], acupuncture+heat-sensitive moxibustion [OR = 9.86, 95%CI (1.77, 55.00), P < 0.05] were more effective than pinaverium bromide in the treatment of IBS-D. Cumulative ranking probability (SUCRA) showed that the comprehensive efficacy of acupuncture and moxibustion (86.8%) and quality of life (QOL) (70.4%) was the best, while the comprehensive efficacy of pinaverium bromide (2.1%) and QOL (16.3%) was the worst. GV20, GV29, ST 25, ST37, ST36, SP6, LR3, and CV12 were used frequently. Conclusion: Acupuncture+sandwiched moxibustion has the best effect on improving the efficacy and QOL of IBS-D patients. Limited by the number and quality of studies, we still need a large sample, multicenter, and high-quality clinical trials to confirm our findings.

Effects of spore powder of ganoderma lucidum on CaSR and apoptosis-related proteins in hippocampus tissue of epilepsy following dementia: A protocol of systematic review.

BACKGROUND: This study will investigate the effects of Spore Powder of Ganoderma Lucidum (SPGL) on CaSR and apoptosis-related proteins (ARP) in hippocampus tissue of epilepsy following dementia. METHODS: This study will retrieve all potential studies from both electronic databases (Cochrane Library, EMBASE, MEDLINE, CINAHL, AMED, and CNKI) and other literature sources to assess the effects of SPGL on CaSR and ARP in hippocampus tissue of epilepsy following dementia. We will search all literature sources from the inception to the present. All eligible case-control studies will be included in this study. Two authors will independently carry out literature selection, data collection, and study quality evaluation. Any divergence will be resolved by another author through discussion. RevMan 5.3 software will be employed for data analysis. RESULTS: This study will summarize existing evidence to assess the effects of SPGL on CaSR and ARP in hippocampus tissue of epilepsy following dementia. CONCLUSIONS: The findings of this study may provide helpful evidence of SPGL on CaSR and ARP in hippocampus tissue of epilepsy following dementia. SYSTEMATIC REVIEW REGISTRATION: INPLASY202070041.

A Review of Low-Intensity Pulsed Ultrasound for Therapeutic Applications.

Ultrasound therapy has a long history of novel applications in medicine. Compared to high-intensity ultrasound used for tissue heating, low-intensity ultrasound has drawn increasing attention recently due to its ability to induce therapeutic changes without biologically significant temperature increase. Low-intensity pulsed ultrasound (LIPUS) is a specific type of ultrasound that delivers at a low intensity and outputs in the mode of pulsed waves. It has minimal thermal effects while maintaining the transmission of acoustic energy to the target tissue, which is able to provide noninvasive physical stimulation for therapeutic applications. LIPUS has been demonstrated to accelerate the healing of fresh fracture, nonunion and delayed union in both animal and clinical studies. The effectiveness of LIPUS for the applications of soft-tissue regeneration and inhibiting inflammatory responses has also been investigated experimentally. Additionally, research has shown that LIPUS is a promising modality for neuromodulation. The purpose of this review is to provide an overview of the recent developments of LIPUS for therapeutic applications, based on the papers that report positive effects, and to present the findings on the understanding of its mechanism. Current available LIPUS devices are also briefly described in this paper.

SGK1/FOXO3 Signaling in Hypothalamic POMC Neurons Mediates Glucocorticoid-Increased Adiposity.

Although the central nervous system has been implicated in glucocorticoid-induced gain of fat mass, the underlying mechanisms are poorly understood. The aim of this study was to investigate the possible involvement of hypothalamic serum- and glucocorticoid-regulated kinase 1 (SGK1) in glucocorticoid-increased adiposity. It is well known that SGK1 expression is induced by acute glucocorticoid treatment, but it is interesting that we found its expression to be decreased in the arcuate nucleus of the hypothalamus, including proopiomelanocortin (POMC) neurons, following chronic dexamethasone (Dex) treatment. To study the role of SGK1 in POMC neurons, we produced mice that developed or experienced adult-onset SGK1 deletion in POMC neurons (PSKO). As observed in Dex-treated mice, PSKO mice exhibited increased adiposity and decreased energy expenditure. Mice overexpressing constitutively active SGK1 in POMC neurons consistently had the opposite phenotype and did not experience Dex-increased adiposity. Finally, Dex decreased hypothalamic α-melanocyte-stimulating hormone (α-MSH) content and its precursor Pomc expression via SGK1/FOXO3 signaling, and intracerebroventricular injection of α-MSH or adenovirus-mediated FOXO3 knockdown in the arcuate nucleus largely reversed the metabolic alterations in PSKO mice. These results demonstrate that POMC SGK1/FOXO3 signaling mediates glucocorticoid-increased adiposity, providing new insights into the mechanistic link between glucocorticoids and fat accumulation and important hints for possible treatment targets for obesity.

Cloning, molecular characterization and expression analysis of insulin-like growth factor binding protein-2 (IGFBP-2) cDNA in goldfish, Carassius auratus.

In the present study, a full-length cDNA encoding the insulin-like growth factor binding protein-2 (IGFBP-2) was cloned from the liver of goldfish (Carassius auratus) by rapid amplification of cDNA ends technique. The goldfish IGFBP-2 cDNA sequence was 1,513 bp long and had an open reading frame of 825 bp encoding a predicted polypeptide of 274 amino acid residues. Semi-quantitative RT-PCR results revealed that goldfish IGFBP-2 mRNA was expressed in all detected tissues. In liver, central nervous system and pituitary gland, goldfish IGFBP-2 expressed at high levels, followed by anterior intestine, middle intestine and kidney. In posterior intestine, ovary, skin, fat, spleen, muscle and gill, the goldfish IGFBP-2 expression levels were very low. Fasting and refeeding experiment showed that the mRNA expression of goldfish IGFBP-2 was up-regulated significantly in liver compared to the fed group and restored rapidly to normal level after refed. However, the mRNA expressions of IGFBP-2 in hypothalamus and pituitary of goldfish were insensitive to fasting. Furthermore, the mRNA expressions of IGFBP-2 in hypothalamus, pituitary and liver were varied in periprandial changes and significantly down-regulated at 2 and 4 h after meal. These results imply that the IGFBP-2 mRNA expression may be associated with anabolic and catabolic metabolism and regulated by metabolic factors in goldfish.

The behavior of pollination drop secretion in Ginkgo biloba L.

Pollination drop (PD) secretion plays a critical role in wind pollination in many gymnosperms. We conducted detailed investigations on PD secretion in Ginkgo biloba, and found that PDs could not form when the micropyle was removed, but were able to form after removal of the shoot, leaves, ovular stalk, or ovular collar. The duration and volume of the PD increased under high relative humidity, but addition of salt or sugar did not affect PD secretion, its size, or its duration. Morphological and anatomical observations showed that many secretion cells at the nucellus tip contributed to secreting the PD after the formation of pollen chamber. Under laboratory conditions, the PD persisted for approximately 10 d if not pollinated, and re-formed five times after it was removed, with the total volume of PDs reaching approximately 0.4 µL. These results suggested that PDs can be continuously secreted by the tip of the nucellus cells during the pollination stage to increase the chance of capturing pollen from the air. Importantly, PD secretion is an independent behavior of the ovule and PDs were produced apoplastically.