Minimizing pain in deer antler removal: Local anaesthetics in ZnO nanoparticle based collagen dressings as a promising solution.

Antler removal in deer is a common practice for various purposes, including meat production and traditional medicine. However, the current industry practice using lidocaine as a local anesthetic has limitations, such as short duration of action and the potential for postoperative infections. In this study, we investigated the performance of a ZnO collagen nanocomposites loaded with local anesthetics to improve wound management and alleviate pain associated with antler removal in red deer. The research involved the preparation of collagen nanocomposites with local anesthetics and testing the drug release rates using in vitro drug release tests. Pharmacokinetic analysis was performed to evaluate the total drug release from the collagen matrix in red deer after velvet removal. Additionally, the analgesic efficacy of these collagen nanocomposite dressings was assessed after antler removal in red deer. Functionalized ZnO nanoparticles were incorporated into collagen fibers to enhance their mechanical stability and prolong drug release. The developed collagen nanocomposites aimed to slowly release local anesthetics and promote wound healing. The findings of this research could have significant implications for improving the pain management and wound healing associated with antler removal in deer. The results obtained from the in vitro drug release tests, pharmacokinetic analysis, and analgesic efficacy evaluations provide valuable insights into the understanding and development of novel approaches for antler removal procedures in red deer. The findings contribute to the advancement of knowledge in this field and lay the foundation for future implementation of improved techniques and protocols for antler removal.

Comparative studies on the chemical composition and pharmacological effects of vinegar-processed antler glue modified from Lei Gong Pao Zhi Lun and traditional water-processed antler glue.

ETHNOPHARMACOLOGICAL RELEVANCE: Antler glue is a classic medicinal to enhance sexual function in traditional Chinese medicine (TCM), which was first recorded in Shen Nong Ben Cao Jing (Shennong's Classic of the Materia Medica). Vinegar-processing is a classic method of processing traditional Chinese medicine. The method of preparing antler glue by boiling antlers in vinegar and then concentrating them is recorded in Lei Gong Pao Zhi Lun (Master Lei's Discourse on Medicinal Processing). In modern times, the typical processing method of antler glue is water extraction and concentration. However, it is not clear whether there is a difference in the effect of these two processing methods on the chemical composition and pharmacological activity of antler glue. AIM OF THE STUDY: The Chinese Pharmacopoeia (2020) records that the processing method of antler glue is water extraction and concentration. But Lei Gong Pao Zhi Lun differs in Chinese Pharmacopoeia (2020), which records the processing method of vinegar extraction and concentration. The effect of the two processing methods on antler glue's chemical composition and pharmacological activity is unknown. So this study aimed to elucidate the difference between different processing methods on the chemical composition and the treatment effect on oligoasthenospermia of antler glue. MATERIALS AND METHODS: So the automatic amino acid analyzer is used to determine the amino acid content of two different processing methods of antler glue. Proteomics was performed to detect the protein components of two different processing methods of antler glue and analyze them. Cyclophosphamide-induced mice models of oligoasthenospermia were used to study the different pharmacological effects of antler glue in two different processing methods. An automatic sperm analyzer observed the quantity and quality of sperm in mice epididymis. Serum sex hormone testosterone (T), luteinizing hormone (LH) and follicle stimulating hormone (FSH) levels in mice were tested using the enzyme-linked immunosorbent assay (ELISA) kits. Hematoxylin-eosin (H&E) staining was used to analyze pathological alterations in mouse testicular tissue. The transcriptome has been used to reveal the potential mechanism of antler glue in treating oligoasthenospermia. Mitochondrial complex activity assay kits were used to assay the activity of mitochondrial respiratory chain complex I-V in mouse testicular tissue. Western blot was used to determine the expression of related proteins in mouse testicular tissue. RESULTS: Vinegar-processing can increase the alanine, proline, and glycine content in antler glue, reduce the length of protein peptides in antler glue, and produce a variety of unique proteins. Vinegar-processed antler glue (VAG) increased sperm density, sperm survival, sperm viability, and serum sex hormone levels in oligozoospermic mice. It reversed testicular damage caused by cyclophosphamide, and the effects were differently superior to those of water-processed antler glue (WAG). In addition, transcriptomics and related experiments have shown that VAG can increase the expression of Ndufa2, Uqcr11, Cox6b1, and Atp5i genes and proteins in mouse testis, thus promoting adenosine diphosphate (ATP) synthesis by increasing the activity of mitochondrial respiratory chain complexes I, III, IV and V. By promoting the oxidative phosphorylation process to produce more ATP, VAG can achieve the therapeutic effect of oligoasthenospermia. CONCLUSION: Vinegar-processing method can increase the content of active ingredients in antler glue. VAG increases ATP levels in the testes by promoting the process of oxidative phosphorylation to treat oligozoospermia.

Gut Microbiota Combined with Metabolomics Reveal the Mechanisms of Sika Deer Antler Protein on Cisplatin-Induced Hepatorenal Injury in Mice.

Cisplatin is a widely used antineoplastic drug, though its adverse effects, particularly its hepatorenal toxicity, limit its long-term application. Sika deer antler is a valuable traditional Chinese medicine (TCM) documented to possess the capacity for tonifying the kidney and regulating the liver, of which the sika deer antler protein is an important active ingredient. In this study, two protein fractions, SVPr1 and SVPr2, of sika deer antler were purified and administered to mice treated with cisplatin, and serum metabolome and fecal microbiota were measured using ultrahigh-performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) and 16S rRNA gene sequencing. SVPr1 and SVPr2 significantly ameliorated cisplatin-induced liver and kidney injury and reduced mitochondrial dysfunction, oxidative stress, inflammatory response, and apoptosis. In addition, SVPr1 and SVPr2 impacted the gut microbiota structure of mice, significantly increasing the relative abundances of Lactobacillus, which deserves to be scrutinized. Moreover, SVPr1 and SVPr2 antagonism of cisplatin-induced hepatorenal injury may be related to the regulation of lysine degradation, tryptophan metabolism, and riboflavin metabolism pathways, significantly altering the levels of L-saccharopine, L-lysine, L-kynurenine, 3-methylindole, xanthurenic acid, riboflavin, and D-ribulose-5-phosphate. A correlation between the differential metabolites and Lactobacillus was identified. These findings increased the knowledge of the gut microbiota-metabolites axis mediated by SVPr1 and SVPr2, and may be able to contribute to the development of new therapeutic strategies for the simultaneous prevention and treatment of liver and kidney injury from cisplatin treatment.

Simplified detection of the species of origin of antler velvets using single-stranded tag hybridization chromatographic printed-array strip.

In this study, we developed a convenient and easy-to-use origin identification method for antler velvets based on a simple DNA extraction technique and single-stranded tag hybridization chromatographic printed-array strip (STH-PAS). The primer sets used to detect Cervus elaphus, Rangifer tarandus, and 12S rRNA did not engage in non-specific reactions such as primer dimer formation. In both the triplex and singleplex assays, the sensitivity was < 1 ng DNA. Moreover, Cervus elaphus DNA could be detected in OTC crude drug products. Although the detection sensitivity resulting from the simplified extraction was slightly lower than that obtained with extraction by conventional methods, the amount of DNA was sufficient even from a small sample. The choice of a triplex or singleplex assay will depend on the purpose of the test. For example, if it is important to determine whether the antler velvet is derived from Cervus elaphus or Rangifer tarandus, a triplex assay is appropriate. If it is necessary to explore whether antler velvet from Cervus elaphus is included in an OTC crude drug product, a singleplex assay using the Cervus elaphus primer set is informative. If it is necessary to explore whether powdered antler velvet includes counterfeit products (from Rangifer tarandus), a singleplex assay employing the Rangifer tarandus primer is appropriate. The singleplex assay detects minor components even at a 1,000:1 ratio. Our study thus demonstrated the utility of a method combining simple DNA extraction with STH-PAS for efficient identification of the origin of antler velvets.

Pharmacodynamic structure of deer antler base protein and its mammary gland hyperplasia inhibition mechanism by mediating Raf-1/MEK/ERK signaling pathway activation.

Mammary gland hyperplasia (MGH) is a common mammary disease whose main pathogenesis is the disruption of estradiol (E2) and progesterone (P) secretion, thereby causing overproliferation of mammary epithelial cells and mammary gland tissue hyperplasia. Deer antler base is a traditional Chinese medicine that has been used for many years to treat MGH. However, its pharmacological mechanism and pharmacodynamic material basis are unclear. In this study, we for the first time used the graded salting method to classify deer antler base protein (CNCP) as CNCP-A, CNCP-B, and CNCP-C and explored the pharmacological mechanism of the anti-MGH properties of CNCP. We found that CNCP could regulate the hormonal levels of E2, P, and follicle stimulating hormone (FSH) and improve the histopathological condition. The potential mechanism might be related to the recombinant C-Raf proto oncogene serine/threonine protein kinase/mitogen-activated protein/extracellular regulated protein kinase (Raf-1/MEK/ERK) signaling pathway. By upregulating the protein expression of the follicle stimulating hormone receptor (FSHR), cyclic adenosine monophosphate (cAMP) and protein kinase A (PKA) inhibited the activation of the downstream Raf-1/MEK/ERK signaling pathway, which in turn inhibited the proliferation of mammary epithelial cells. We analyzed the physicochemical properties of CNCP-A, CNCP-B, and CNCP-C and obtained CNCP-C-I by column chromatographic purification of the best pharmacophore protein CNCP. Using high-performance liquid gel filtration chromatography (HPGFC), we determined the molecular weight of CNCP-C-I and identified it by high-performance liquid tandem mass spectrometry (LC-MS/MS) to obtain the first match for a high confidence protein KRT1. This study provides a theoretical basis for the development of effective traditional Chinese medicines with low toxicity levels for the prevention and treatment of mammary gland diseases.

Structural characteristics of a low molecular weight velvet antler protein and the anti-tumor activity on S180 tumor-bearing mice.

Velvet antler is a traditional Chinese medicine with various pharmacological values, which is an important raw material for traditional Chinese medicinal wine. Nevertheless, the chemical compositions and bioactivities of velvet antler residue used for making medicinal wine are rarely reported, leading to a waste of resources. In this study, a velvet antler protein (VA-pro) was extracted from velvet antler residue by simulating the gastrointestinal digestion, and its composition, structural characteristics and in vivo anti-tumor activities were determined and investigated. VA-pro possessed high purity with a relatively low molecular weight as 22.589 kDa under HPLC, one- and two-dimensional electrophoresis, and it contained high contents of Pro, Gly, Glu and Ala. Besides, the secondary structure of VA-pro was dominated by ß-turn and ß-sheet, and VA-pro possessed similar protein sequence, isoelectric point and amino acid compositions to hypothetical protein G4228_020061. The in vivo results substantiated that VA-pro could improve the body weights and immune organ indices, increase the expressions of sera cytokines and regulate the distributions of T and B lymphocytes subsets in peripheral blood of S180 tumor-bearing mice. Furthermore, VA-pro could effectively inhibit solid S180 tumors growth by inducing S phase cell cycle arrest mediated through mitochondria. To summarize, our study provided theoretical support that VA-pro had the potential to be used as an immunopotentiator in immunocompromised or cancer-bearing hosts.

[Detection of chondroitin sulfate in Cervi Cornu Pantotrichum and Cervi Cornu of different specifications and its application in quality evaluation].

The present study comprehensively compared the content of chondroitin sulfate in Cervi Cornu Pantotrichum(CCP) and Cervi Cornu(CC) of different specifications and explored the feasibility of chondroitin sulfate as an indicator to distinguish between CCP and CC. Twenty-two batches of CCP of different specifications(two-branched velvet antler and three-branched velvet antler) from 15 habitats, CC from 6 habitats, and 60 batches of CCP slices prepared from different parts(wax slices, powder slices, gauze slices, and bone slices) were collected. High-performance liquid chromatography(HPLC) was used to determine chondroitin sulfate content in CCP and CC of different specifications. Cluster analysis was used to classify CCP slices of different specifications. The results showed that CCP contained abundant chondroitin sulfate. The average content of chondroitin sulfate was 2.35 mg·g~(-1) in two-branched velvet antler and 1.79 mg·g~(-1) in three-branched velvet antler, significantly higher than 0.11 mg·g~(-1) in CC. Chondroitin sulfate content in wax slices, powder slices, gauze slices, and bone slices were 7.81, 8.39, 1.33, and 0.54 mg·g~(-1), respectively. Cluster analysis showed that gauze slices and bone slices could be clustered into one category and distinguished from wax slices and powder slices. CCP slices prepared from different parts could be separated well through chondroitin sulfate content. Based on the five principles of Q-marker selection, chondroitin sulfate can be used as a potential Q-marker for the identification of CCP and CC, as well as a potential quality indicator for CCP slices of different specifications(wax slices, powder slices, gauze slices, and bone slices). This research provides data support for CCP quality evaluation.

Deer antler extract promotes tibia fracture healing in mice by activating BMP-2/SMAD4 signaling pathway.

BACKGROUND: Deer antler is a traditional Chinese medicine with the function of tonifying kidney and strengthening bone, which is often used to treat orthopedic diseases. METHODS: Eight-week-old C57BL/6 mice were used as the fixation model of open tibial fracture with intramedullary nail. The mice were treated with deer antler extract (DAE) or PBS by oral gavage once daily. The tibial fracture samples were collected and performed to the tissue analysis, including X-ray, micro-CT, histology, qRT-PCR, immunohistochemistry. MC3T3-E1 cells were used to detect the effect of deer antler extract on ability of cell proliferation and migration by CCK-8 assay and cell scratch test. RESULTS: Imaging and micro-CT showed that DAE could promote the healing of tibial fracture in mice, and histological analysis showed that DAE could promote the transformation of cartilage callus to bone callus in fracture area. The results of qRT-PCR and immunohistochemistry showed that DAE could promote intrachondral ossification in fracture zone and the mechanism of promoting fracture healing may be related to the activation of BMP-2/SMAD4 signaling pathway. In the cytological experiment of DAE, it can be found that DAE promoted the proliferation of MC3T3-E1 cells and the migration of MC3T3-E1 cells at a certain concentration, which is also related to the promotion of fracture healing by DAE. CONCLUSION: DAE can promote fracture healing by activating BMP-2/SMAD4 signaling pathway. DAE has the potential to be used in clinic as an important means of promoting fracture healing.

Characterization of Cervus timorensis velvet antler and its effect on biofilm formation of Candida species.

Oral biofilms comprise extracellular polysaccharides and polymicrobial microorganisms. The objectives of the study were to characterize the deer velvet antler (DVA) compounds and their effect on Candida species biofilm formation with the hypothesis that DVA inhibits the biofilm of Candida spp. Liquid Chromatography-Quadrupole Time of Flight-Mass Spectrometry (LC-QTOF-MS) was conducted to characterize the DVA compounds. To study the effect of DVA on biofilm, Candida albicans ATCC MYA-4901 (ALT5), AIDS isolate (ALC2), oral cancer isolate (ALC3), C. dubliniensis ATCC MYA-2975, C. glabrata ATCC 90030, C. krusei 14 243, C. lusitaniae ATCC 34449, C. parapsilosis ATCC 22019, and C. tropicalis ATCC 13803 were inoculated with DVA in separate wells of a 96-well plate containing RPMI-1640 followed by 72 h incubation. A total of 45 compounds were detected in the DVA extract. C. lusitaniae exhibited a higher percentage of biofilm biomass reduction when treated with DVA extract (66.10% ± 5.33), followed by ALC3 (44.12% ± 6.24). However, C. glabrata, C. krusei, and C. parapsilosis showed no reduction in biofilm biomass after being treated with DVA extract. Most Candida strains also exhibited decreased total cell count when treated with DVA extract, except for ALC3 and C. krusei. ALT5 had the lowest total cell count (0.17 × 105 cells/ml) when cultured with DVA extract. In conclusion, DVA extract inhibits Candida spp. biofilm formation except for C. glabrata, C. krusei, and C. parapsilosis.

The study determines deer velvet antler (DVA) compounds and their effect on Candida species biofilm formation. A total of 45 compounds were detected in the DVA extract. Most Candida spp. exhibited a higher percentage of biofilm reduction and decreased total cell count when treated with DVA extract.

Peptide-Calcium Chelate from Antler (Cervus elaphus) Bone Enhances Calcium Absorption in Intestinal Caco-2 Cells and D-gal-Induced Aging Mouse Model.

Antler bone calcium (AB-Ca) and bioactive peptides (ABPs) were extracted from antler bones (Cervus elaphus) to maximize their value. In this study, 0.14 g calcium was obtained from 1 g antler bone. The peptide-calcium chelate rate was 53.68 ± 1.80%, and the Gly, Pro, and Glu in ABPs were identified to donate most to the increased calcium affinity through the mass spectrometry. Fourier transform infrared spectroscopy showed that calcium predominantly interacted with amino nitrogen atoms and carboxyl oxygen atoms, thereby generating a peptide-calcium chelate. The peptide-calcium chelates were characterized using scanning electron microscopy. A Caco-2 cell monolayer model showed that ABPs significantly increased calcium transport. Furthermore, the D-gal-induced aging mouse model indicated that the ABPs + AB-Ca group showed higher Ca and PINP levels, lower P, ALP, and CTX-1content in serum, and considerably higher tibia index and tibia calcium content. Results showed that ABPs + AB-Ca increased bone formation and inhibited bone resorption, thereby providing calcium supplements for ameliorating senile osteoporosis (SOP).

Deer Velvet Antler Extracts Exert Anti-Inflammatory and Anti-Arthritic Effects on Human Rheumatoid Arthritis Fibroblast-Like Synoviocytes and Distinct Mouse Arthritis.

Rheumatoid arthritis (RA) is a chronic autoimmune disease that causes joint deformity and disability. Deer velvet antler (DA), a traditional Chinese medicine, has been used to treat various types of arthritis for several thousands of years, but the underlying mechanisms are unknown. Herein, we investigated the anti-arthritic and anti-inflammatory effects of DA in vitro and in vivo. The ethyl acetate layer of DA ethanol extract (DA-EE-EA) was used to treat tumor necrosis factor (TNF)-[Formula: see text]-stimulated fibroblast-like synoviocyte MH7A cells, collagen-induced arthritis DBA/1 mice, and SKG mice with zymosan-induced arthritis. DA-EE-EA reduced nitric oxide production, prostaglandin E2 levels, and levels of pro-inflammatory cytokines including interleukin (IL)-1[Formula: see text], IL-6, and IL-8 in MH7A cells. DA-EE-EA also downregulated the phosphorylation of mitogen-activated protein kinase p38 and c-Jun N-terminal kinase and the translocation of nuclear factor kappa B p65. Intraperitoneal injection of DA-EE-EA for 3 weeks substantially reduced clinical arthritis scores in vivo models. Pathohistological images of the hind paws showed that DA-EE-EA reduced immune cell infiltration, synovial hyperplasia, and cartilage damage. The levels of pro-inflammatory cytokines, such as tumor necrosis factor alpha, IL-1[Formula: see text], IL-6, IL-8, IL-17A, and interferon-gamma, decreased in the hind paw homogenates of DA-EE-EA-treated mice. We also identified several potential components, such as hexadecanamide, oleamide, erucamide, and lysophosphatidylcholines, that might contribute to the anti-inflammatory effects of DA-EE-EA. In conclusion, DA-EE-EA has the potential to treat RA by regulating inflammatory responses. However, the individual components of DA-EE-EA and the underlying anti-inflammatory mechanisms need further investigation in future studies.

Deer antler extracts reduce amyloid-beta toxicity in a Caenorhabditis elegans model of Alzheimer's disease.

ETHNOPHARMACOLOGICAL RELEVANCE: Velvet antler extracts (VAE) are composed of a variety of active substances and growth factors, and have been reported to improve sleep quality and memory. AIM OF THE STUDY: We aimed to explore the protective effects and mechanism of action for VAE on Alzheimer's disease (AD) using a transgenic Caenorhabditis elegans model. MATERIALS AND METHODS: C. elegans were cultivated at 40% relative humidity on solid nematode growth medium (NGM) containing live E. coli (OP50) as the food source, with Strain N2 (normal) held at 20 °C and the CL4176s (transgenic) held at 16 °C. AD-like aggregation of Aß peptide in the CL4176s strain is induced by lifting the temperature to 25 °C. Nematodes were treated with three types of VAEs and Resveratrol (positive control). Analyses included qRT-PCR for quantification of gene transcripts of interest; ELISA for measuring levels of amyloid-ß protein; Thioflavin T fluorescent staining for localizing Aß depositions; assays for reactive oxygen species (ROS) and superoxide dismutase activity (SOD). RESULTS: VAEs reduced ß-amyloid peptide (Aß) toxicity in the transgenic C. elegans model. An enzymatically-digested VAE (EDVAE) was superior to both a cold-water VAE (CWVAE) and a hot-water VAE (HWVAE) from the same velvet antler. EDVAE treatment reduced the severity of the Aß-induced paralysis phenotype and decreased the amount of Aß deposits in the AD model nematodes, and these effects were found to be significantly better than that of the positive control Resveratrol. In addition, EDVAE treatment reduced production of ROS (induced by Aß), enhanced SOD activity, and elevated expression levels of antioxidant-related transcription factors, although it is not known whether these effects were achieved directly or indirectly. CONCLUSION: EDVAE had a protective role in Aß-induced toxicity in the transgenic AD nematodes, possibly through reducing accumulation of toxic Aß and enhancing the ability of nematodes to resist oxidative stress. Thus, EDVAE has potential to be an effective treatment to relieve the symptoms of AD.

The anti-aging effect of velvet antler polypeptide is dependent on modulation of the gut microbiota and regulation of the PPARα/APOE4 pathway.

We investigated the anti-aging effects of velvet antler polypeptide on D-galactose (D-gal)-induced aging mice. D-gal-induced aging mice were established and randomly divided into five groups, the control, model, vitamin E (VE), velvet antler polypeptide low-dose and velvet antler polypeptide high-dose groups. The Morris water maze test was used to evaluate the learning and memory abilities of aging mice. Hippocampal neurons were observed via hematoxylin-eosin staining and transmission electron microscopy. Biochemical methods were used to detect the activities of superoxide dismutase, malonaldehyde and other enzymes and evaluate the influence of velvet antler polypeptide on the antioxidant capacity of aging mice. Using 16S rRNA gene sequencing and meristem technology, we assessed the effect of velvet antler polypeptide on aging mice's intestinal flora and fatty acid metabolism. The experimental results showed that velvet antler polypeptide could significantly improve aging mice's learning and cognitive abilities, increase the activities of superoxide dismutase, glutathione peroxidase, and catalase in the serum decrease the malonaldehyde content. Intestinal microecological analysis showed that velvet antler polypeptide could significantly increase the beneficial bacterial genus Lactobacillus abundance. Western blot analysis further demonstrated that velvet antler polypeptide could promote fatty acid metabolism by activating peroxisome proliferator-activated receptor α (PPARα) and upregulating the expression of the downstream enzymes carnitine-palmitoyl transferase-1 A and acyl-CoA oxidase 1 while downregulating that of apolipoprotein E4 (APOE4), thereby reducing fatty acid accumulation and increasing adenosine-triphosphate (ATP) production. Therefore, velvet antler polypeptide improves the intestinal microecology and activates the PPARα/APOE4 pathway to regulate fatty acid metabolism.

Efficacy of Chinese herbal prescriptions containing Ejiao or Velvet antler for management of uterine fibroids: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: To evaluate the efficacy and safety of the controversial Chinese herbal prescriptions containing Ejiao or Velvet antler (VA) in the treatment of uterine fibroids. METHODS: We searched 4 famous Chinese databases, the Chinese Clinical Trial Registry, PubMed, Cochrane Central, Google Scholar, Embase, and J-STAGE up to July 2019. We included all eligible randomized controlled trials (RCTs) which compared Chinese herbal prescriptions containing Ejiao or VA (E/VA) with placebo, pharmaceutical intervention, surgery, or other traditional Chinese medicines (TCMs) for uterine fibroids and assessed the risk of bias according to the Cochrane Collaboration's tool. The software Review Manager (RevMan) 5.1 was used for data analysis. RESULTS: A total of 9 RCTs involving 844 patients were identified. Meta-analyses demonstrated that TCM (E/VA) plus mifepristone reduced the volume of uterine fibroids to a greater degree than mifepristone alone [standardized mean difference (SMD): 0.59, 95% CI: 0.33 to 0.85, P<0.00001, I2=50%]; TCM (E/VA) did not enlarge the volume of fibroids when menopausal hormone therapy (MHT) significantly increased the volume (SMD: 1.06, 95% CI: 0.73 to 1.38, P<0.00001, I2=0. The uterine volume change difference was larger via combination therapy of TCM (E/VA) and mifepristone than that of mifepristone (SMD: 0.29, 95% CI: 0.09 to 0.49, P=0.005, I2=0%). The TCM (E/VA) group of had an advantage over the control group in the improvement of fibroid-related symptoms [relative risk (RR): 1.24, 95% CI: 1.15 to 1.35, P<0.00001, I2=0%]. It was found that TCM (E/VA) plus mifepristone could lower estradiol (E2) levels to a greater degree than mifepristone alone (SMD: 1.63, 95% CI: 0.42 to 2.83, P=0.008, I2=97%), as well as progesterone (P) level (SMD: 0.79, 95% CI: 0.55 to 1.04, P<0.00001, I2=43%) in non-menopausal women. A total of 5 studies reported adverse events (AEs), the TCM (E/VA) group was potentially safer than the control group, with lower incidence of AEs (RR: 0.24, 95% CI: 0.15 to 0.40, P<0.00001, I2=25.8%). DISCUSSION: TCM prescriptions containing E/VA seemed superior to the control group in shrinking the volume of uterine fibroids and uterus, improving related symptoms, and reducing non-menopausal women's E2 and P levels, with lower incidence of AEs.

Antlerogenic stem cells extract accelerate chronic wound healing: a preliminary study.

BACKGROUND: Chronic wounds constitute a significant medical and social problem. Chronic wound treatment may be supported by various techniques, such as negative pressure therapy, phototherapy or stem cells therapy, yet most of those supporting therapies need more evidence to be used for standard wound care. Current study covers the use of sonicated Antlerogenic Stem Cells (ASC) extract on chronic wounds. METHODS: Study was performed on 20 dermatological patients with venous leg ulcers, divided into two groups - treated with and without ASC extract respectively. The area and circumference of the wounds during the follow-up visits were measured on the wound imprint. Dynamics of wound healing was determined and compared between control and study group; statistics includes changes in absolute values (wound area, circumference), as well as relative (percentage of wound decrease, circumference/area ratio) and their change in time. For the purpose of Ki-67 immunohistochemical staining, sections were sampled from the wound edge at distinct check-points during therapy. Results of both groups were compared with Student test or Mann-Whitney test, depending on results distribution. RESULTS: Besides Ki-67 expression, all tested wound healing parameters (including relative and absolute wound decrease and changes in circumference/area ratio) were statistically significant more favorable in experimental group. CONCLUSION: ASC extract significantly supported standard chronic wound treatment. Due to small population of study the results should be considered preliminary, yet promising for further research.

Deer antler extract potentially facilitates xiphoid cartilage growth and regeneration and prevents inflammatory susceptibility by regulating multiple functional genes.

BACKGROUND: Deer antler is a zoological exception due to its fantastic characteristics, including amazing growth rate and repeatable regeneration. Deer antler has been used as a key ingredient in traditional Chinese medicine relating to kidney and bone health for centuries. The aim of this study was to dissect the molecular regulation of deer antler extract (DAE) on xiphoid cartilage (XC). METHODS: The DAE used in this experiment was same as the one that was prepared as previously described. The specific pathogen-free (SPF) grade Sprague-Dawley (SD) rats were randomly divided into blank group (n =10) and DAE group (n =10) after 1-week adaptive feeding. The DAE used in this experiment was same as the one that was prepared as previously described. The rats in DAE group were fed with DAE for 3 weeks at a dose of 0.2 g/kg per day according to the body surface area normalization method, and the rats in blank group were fed with drinking water. Total RNA was extracted from XC located in the most distal edge of the sternum. Illumina RNA sequencing (RNA-seq) in combination with quantitative real-time polymerase chain reaction (qRT-PCR) validation assay was carried out to dissect the molecular regulation of DAE on XC. RESULTS: We demonstrated that DAE significantly increased the expression levels of DEGs involved in cartilage growth and regeneration, but decreased the expression levels of DEGs involved in inflammation, and mildly increased the expression levels of DEGs involved in chondrogenesis and chondrocyte proliferation. CONCLUSIONS: Our findings suggest that DAE might serve as a complementary therapeutic regent for cartilage growth and regeneration to treat cartilage degenerative disease, such as osteoarthritis.

Investigating the molecular control of deer antler extract on articular cartilage.

BACKGROUND: Deer antler is considered as a precious traditional Chinese medicinal material and has been widely used to reinforce kidney's yang, nourish essence, and strengthen bone function. The most prominent bioactive components in deer antler are water-soluble proteins that play potential roles in bone formation and repair. The aim of this study was to explore the molecular control and therapeutic targets of deer antler extract (DAE) on articular cartilage. METHODS: DAE was prepared as previously described. All rats were randomly divided into Blank group and DAE group (10 rats per group) after 7-day adaptive feeding. The rats in DAE group were orally administrated with DAE at a dose of 0.2 g/kg per day for 3 weeks, and the rats in Blank group were fed with drinking water. Total RNA was isolated from the articular cartilage of knee joints. RNA sequencing (RNA-seq) experiment combined with quantitative real-time polymerase chain reaction (qRT-PCR) verification assay was carried out to explore the molecular control and therapeutic targets of DAE on articular cartilage. RESULTS: We demonstrated that DAE significantly increased the expression levels of functional genes involved in cartilage formation, growth, and repair and decreased the expression levels of susceptibility genes involved in the pathophysiology of osteoarthritis. CONCLUSIONS: DAE might serve as a candidate supplement for maintaining cartilage homeostasis and preventing cartilage degeneration and inflammation. These effects were possibly achieved by accelerating the expression of functional genes involved in chondrocyte commitment, survival, proliferation, and differentiation and suppressing the expression of susceptibility genes involved in the pathophysiology of osteoarthritis. Thus, our findings will contribute towards deepening the knowledge about the molecular control and therapeutic targets of DAE on the treatment of cartilage-related diseases.

Hard antler extract inhibits invasion and epithelial-mesenchymal transition of triple-negative and Her-2+ breast cancer cells by attenuating nuclear factor-κB signaling.

ETHNOPHARMACOLOGICAL RELEVANCE: Hard antler extract (HAE) is a traditional Chinese medicine and has potent antitumor, antioxidative, anti-inflammatory, and immunomodulatory activities. Previous studies have demonstrated that HAE can inhibit human prostate cancer metastasis and murine breast cancer proliferation. However, the effect of HAE on human breast cancer cells has not been clarified. AIM OF THE STUDY: To investigate the effects and underlying mechanism of HAE on self-renewal of stem-like cells and spontaneous and transforming growth factor (TGF)-ß1-enhanced wound healing, invasion and epithelial-mesenchymal transition (EMT) in breast cancer cells. METHODS: HAE was prepared from sika deer by sequential enzymatic digestions and the active compounds were determined by HPLC. The effects of HAE on the viability, mammosphere formation, wound healing and invasion of MDA-MB-231 and SK-BR3 cells were determined. The impact of HAE treatment on spontaneous and TGF-ß1-promoted EMT and the nuclear factor (NF)-κB signaling in breast cancer cells was examined by quantitative RT-PCR and western blotting. RESULTS: Treatment with HAE at varying concentrations did not change the viability of breast cancer cells. However, HAE at 0.25 or 0.5 mg/mL significantly reduced the number and size of formed mammospheres, and inhibited spontaneous and TGF-ß1-enhanced wound healing, invasion and EMT in MDA-MB-231 and SK-BR3 cells in a dose-dependent manner. TGF-ß1 treatment significantly decreased IκBα expression and increased NF-kBp65 phosphorylation in breast cancer cells, indicating that TGF-ß1 enhanced NF-κB signaling. In contrast, HAE treatment attenuated the spontaneous and TGF-ß1-enhanced NF-κB signaling in breast cancer cells. CONCLUSION: Our data indicated that HAE inhibited the self-renewal of stem-like cells and spontaneous and TGF-ß1-enhanced wound healing, invasion and EMT in breast cancer cells by attenuating the NF-κB signaling in vitro.

Split-based points from the Swabian Jura highlight Aurignacian regional signatures.

The systematic use of antlers and other osseous materials by modern humans marks a set of cultural and technological innovations in the early Upper Paleolithic, as is seen most clearly in the Aurignacian. Split-based points, which are one of the most common osseous tools, are present throughout most regions where the Aurignacian is documented. Using results from recent and ongoing excavations at Geißenklösterle, Hohle Fels and Vogelherd, we nearly tripled the sample of split-based points from 31 to 87 specimens, and thereby enhance our understanding of the technological economy surrounding the production of osseous tools. Aurignacian people of the Swabian Jura typically left spit-based points at sites that appear to be base camps rich with numerous examples of personal ornaments, figurative art, symbolic imagery, and musical instruments. The artifact assemblages from SW Germany highlight a production sequence that resembles that of SW France and Cantabria, except for the absence of tongued pieces. Our study documents the life histories of osseous tools and demonstrates templates for manufacture, use, recycling, and discard of these archetypal artifacts from the Aurignacian. The study also underlines the diversified repertoire of modern humans in cultural and technological realms highlighting their adaptive capabilities.