Rehabilitations for maternal diastasis recti abdominis: An update on therapeutic directions.

Diastasis recti abdominis (DRA) affects a significant number of postpartum women, while its treatments are still under debate. This study aimed to systematically evaluate the effectiveness of rehabilitation training programs for postpartum DRA treatment. Four databases were systematically searched to identify eligible studies published up to February 1, 2023. We followed the PRISMA for scoping reviews guideline in this study. The characteristics and the main findings of the included studies were extracted. Sixteen studies enrolling 1129 women during the ante- and/or postnatal period were included. The common rehabilitation training for DRA included physical exercise, non-exercise physical therapy, acupuncture, and electrotherapy. The presence of DRA could be diagnosed by ultrasound, caliper, or palpation, of which ultrasound had the best reliability. Besides, these assessments could also be used for evaluating the therapeutic efficacy after the rehabilitation training programs. Several studies concluded that patients with DRA could be effectively improved by specific interventions. But a few included studies revealed rehabilitation training might be not more effective than no interventions when treating DRA. For example, some investigators did not recommend physical exercise for DRA patients due to this intervention during pregnancy kept the linea alba less stressed by maintaining abdominal tone, strength, and control, and therefore might aggravate DRA. However, it should be noted that this evidence was derived from limited studies (16/60, 27 % papers) with small samples. To some extent, women with postpartum DRA can benefit from the specific rehabilitation regimen by alleviating postpartum inter-rectus distance. Further research is still warranted to propose strategies for improving postpartum DRA.

Acupuncture for Osteoporosis: a Review of Its Clinical and Preclinical Studies.

Acupuncture has gained growing attention in the management of osteoporosis (OP). However, a comprehensive review has not yet been conducted on the efficacy and challenges of acupuncture in preliminary research and clinical trials. Therefore, an extensive literature search was conducted using electronic databases, including PubMed (www.ncbi.nlm.nih.gov/pubmed), CNKI (www.cnki.net), and Web of Science, for studies published from the beginning of 2000 to the end of May 2022. Combinations of synonyms for OP, acupuncture, traditional Chinese medicine, clinical trial, preclinical study, and animal experiments were searched. A total of 290 papers were consulted, including 115 reviews, 109 clinical observations, and 66 preclinical studies. There is accumulating evidence to support the beneficial role of acupuncture in preserving bone quality and relieving clinical symptoms based on clinical and preclinical investigations. The top ten most commonly used acupoints are BL23, ST36, BL20, BL11, CV4, GV4, SP 6, KI3, BL18, and GB39. The underlying mechanisms behind the benefits of acupuncture may be linked with the regulation of the hypothalamic-pituitary-gonadal (adrenal) axis and activation of the Wnt/ß-catenin and OPG/RANKL/RANK signaling pathways. In summary, strong evidence may still come from prospective and well-designed clinical trials to shed light on the potential role of acupuncture in preserving bone loss. Future investigations are needed to explore the potential underlying mechanisms, long-term clinical efficacy, and compliance of acupuncture in OP management.

The Antigastric Cancer Effect of Triptolide is Associated With H19/NF-κB/FLIP Axis.

Background and Objective: Triptolide (TP), one of the fat-soluble components extracted from the Chinese medicinal herb Tripterygium wilfordii Hook F. (TWHF), possesses strong antitumor bioactivities, but its dose-dependent side effects restrict its wide application. This study was designed to investigate whether inflammatory factors increased the antitumor effects of the nontoxic dose of TP on gastric cancer cells and tried to explore the possible molecular mechanisms. Method: AGS and MKN45 cells were treated with different doses of TP and TNF-α. Cell viability and apoptosis were detected in vitro. In addition, NF-κB mediated prosurvival signals and cytoprotective proteins, especially FLICE-inhibitory protein (FLIP), were detected to determine their effects on TP/TNF-α-induced apoptosis. Moreover, the function of lncRNA H19/miR-204-5p/NF-κB/FLIP axis was investigated in vitro, and the antigastric cancer effect of TP plus TNF-α was proved in the mice xenograft model. Result: In vitro experimental results showed that TP pretreatment promoted apoptosis in AGS and MKN45 cells upon TNF-α exposure. TP/TNF-α-mediated apoptosis was partly mediated by the inhibitory effect of NF-κB-mediated FLIP expression. Oncogene H19 lying in the upstream pathway of NF-κB played a vital role upon TNF-α exposure, and bioinformatics analysis proved that H19 participated in TP/TNF-α-induced apoptosis via binding of miR-204-5p. Lastly, a low dose of TP and TNF-α inhibited the tumor weight and tumor volume of AGS and MKN45 cells in vivo. Conclusion: TP pretreatment increased apoptosis in TNF-α-stimulated gastric cancer cells, which are dependent on the disruption of the H19/miR-204-5p/NF-κB/FLIP axis. Cotreatment of TP and TNF-α is a better option for enhancing the anticancer effect and lowering the side effect of TP.

Porous organic framework as coating for stir bar sorptive extraction of carbamate pesticides from corn and potato samples.

Three porous organic frameworks (POFs) were synthesized by the reaction between phloroglucinol and 1,4-phthalaldehyde, 4,4'-biphenyldialdehyde or tris-(4-formylphenyl) amine; the products are named as POF-a, POF-b and POF-c, respectively. They were used to prepare POFs coated stir bars respectively for the extraction of four carbamate pesticides (CMPs). POF-c coated stir bar exhibited better adsorption performance than POF-a/b coated stir bar and commercial stir bars, probably due to the stronger conjugated structure and hydrophobicity of POF-c, and resultant hydrophobic, π-π and hydrogen bonding interactions between them. The adsorption mechanism for target CMPs was verified by characterization techniques and molecular dynamics simulation. A method of POF-c coated stir bar sorptive extraction-high performance liquid chromatography-variable wavelength ultraviolet detector was developed for the analysis of four CMPs in corn and potato samples. Under the optimal conditions, LODs of the method were between 0.017 and 0.048 µg/L, and the linear range for four CMPs was 0.1/0.2-200 µg/L.

Study on the SHP2-Mediated Mechanism of Promoting Spermatogenesis Induced by Active Compounds of Eucommiae Folium in Mice.

Spermatogenesis directly determines the reproductive capacity of male animals. With the development of society, the increasing pressure on people's lives and changes in the living environment, male fertility is declining. The leaf of Eucommia ulmoides Oliv. (Eucommiae Folium, EF) was recorded in the 2020 Chinese Pharmacopoeia and was used in traditional Chinese medicine as a tonic. In recent years, EF has been reported to improve spermatogenesis, but the mechanisms of EF remain was poorly characterized. In this study, the effect of EF ethanol extract (EFEE) on spermatogenesis was tested in mice. Chemical components related to spermatogenesis in EF were predicted by network pharmacology. The biological activity of the predicted chemical components was measured by the proliferation of C18-4 spermatogonial stem cells (SSCs) and the testosterone secretion of TM3 leydig cells. The biological activity of chlorogenic acid (CGA), the active compound in EF, was tested in vivo. The cell cycle was analysed by flow cytometry. Testosterone secretion was detected by ELISA. RNA interference (RNAi) was used to detect the effect of key genes on cell biological activity. Western blotting, qRT-PCR and immunofluorescence staining were used to analyse the molecular mechanism of related biological activities. The results showed that EFEE and CGA could improve spermatogenesis in mice. Furthermore, the main mechanism was that CGA promoted SSC proliferation, self-renewal and Leydig cell testosterone secretion by promoting the expression of SHP2 and activating the downstream signaling pathways involved in these biological processes. This study provided strong evidence for elucidating the mechanism by which EF promotes the spermatogenesis in mice and a new theoretical basis for dealing with the decrease in male reproductive capacity.

BaZiBuShen alleviates cognitive deficits and regulates Sirt6/NRF2/HO-1 and Sirt6/P53-PGC-1α-TERT signaling pathways in aging mice.

ETHNOPHARMACOLOGICAL RELEVANCE: BaZiBuShen formula (BZBS) is clinically used to counteract mental fatigue and to retard the aging process. Brain aging echoes in major risks of human sufferings and has become one of the main challenges to our societies and the health-care systems. AIM OF THE STUDY: To investigate the effect and mode of action of BZBS on aging-associated cognitive impairments. MATERIALS AND METHODS: BZBS was orally administered to D-galactose and NaNO2-induced aging mice. Premature senescence was assessed using the Morris water maze, step-down type passive avoidance, and pole-climbing tests. Telomere length was examined by qPCR analysis. Telomerase activity was assessed using PCR ELISA assay. Mitochondrial complex IV activity was examined by biochemical test. The levels of redox and immune status were determined by ELISA or biochemical assay. The expressions of sirtuin 6 (Sirt6), peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α), P53, telomerase reverse transcriptase (TERT), heme oxygenase-1 (HO-1), phospho(p)-nuclear factor erythroid-2 related factor 2 (NRF2), caspase-3, Bcl-2 associated x (Bax), and B-cell lymphoma-2 (Bcl-2) in the cerebral cortex were examined by Western blot and/or immunohistochemical staining. RESULTS: BZBS intervention ameliorated reduced brain performances in aging mice, including memory, cognitive, and motor functions. In addition, BZBS administration to aging mice preserved redox homeostasis, attenuated immunosenescence, and maintained telomerase activity and telomere length. Moreover, BZBS treatment were associated with a declines in P53, caspase-3, Bax expressions and an increase in Sirt6, p-HO-1, p-NRF2, PGC-1α, and Bcl-2 expressions in the brains of this rapid aging mouse. CONCLUSIONS: BZBS attenuates premature senescence possibly via the preservation of redox homeostasis and telomere integrity, and inhibition of apoptosis in rapid aging mouse. The mechanism governing the alterations may be associated with through the activation of Sirt6/NRF2/HO-1 and Sirt6/P53-PGC-1α-TERT signaling pathways. The results suggest that BZBS may provide a novel strategy for confronting aging and age-associated diseases.

A comprehensive review on the phytochemistry, pharmacokinetics, and antidiabetic effect of Ginseng.

BACKGROUND: Radix Ginseng, one of the well-known medicinal herbs, has been used in the management of diabetes and its complications for more than 1000 years. PURPOSE: The aim of this review is devoted to summarize the phytochemistry and pharmacokinetics of Ginseng, and provide evidence for the antidiabetic effects of Ginseng and its ingredients as well as the underlying mechanisms involved. METHODS: For the purpose of this review, the following databases were consulted: the PubMed Database (https://pubmed.ncbi.nlm.nih.gov), Chinese National Knowledge Infrastructure (http://www.cnki.net), National Science and Technology Library (http://www.nstl.gov.cn/), Wanfang Data (http://www.wanfangdata.com.cn/) and the Web of Science Database (http://apps.webofknowledge.com/). RESULTS: Ginseng exhibits glucose-lowering effects in different diabetic animal models. In addition, Ginseng may prevent the development of diabetic complications, including liver, pancreas, adipose tissue, skeletal muscle, nephropathy, cardiomyopathy, retinopathy, atherosclerosis and others. The main ingredients of Ginseng include ginsenosides and polysaccharides. The underlying mechanisms whereby this herb exerts antidiabetic activities may be attributed to the regulation of multiple signaling pathways, including IRS1/PI3K/AKT, LKB1/AMPK/FoxO1, AGEs/RAGE, MAPK/ERK, NF-κB, PPARδ/STAT3, cAMP/PKA/CERB and HIF-1α/VEGF, etc. The pharmacokinetic profiles of ginsenosides provide valuable information on therapeutic efficacy of Ginseng in diabetes. Although Ginseng is well-tolerated, dietary consumption of this herb should follow the doctors' advice. CONCLUSION: Ginseng may offer an alternative strategy in protection against diabetes and its complications through the regulations of the multi-targets via various signaling pathways. Efforts to understand the underlying mechanisms with strictly-controlled animal models, combined with well-designed clinical trials and pharmacokinetic evaluation, will be important subjects of the further investigations and weigh in translational value of this herb in diabetes management.

Fructus Ligustri Lucidi aqueous extract promotes calcium balance and short-chain fatty acids production in ovariectomized rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Fructus Ligustri Lucidi (FLL) is an edible herb with anti-osteoporotic activity, yet whether and how the aqueous extract of this herb affect calcium metabolism in preservation of bone quality remain unclear. AIM OF THE STUDY: To investigate the effects of FLL aqueous extract on calcium balance and short-chain fatty acids (SCFAs) production in ovariectomized (OVX) rats. MATERIALS AND METHODS: OVX rats were daily and orally administrated with FLL aqueous extract (3.5 g/kg) for 14 weeks. The levels of N-terminal propeptide of type I collagen (PINP) and C-terminal telopeptide of type I collagen (CTx-I) in rat serum were evaluated by ELISA assays. The concentration of calcium in serum, urine, and feces were determined by biochemical assays. Bone quality was determined by Micro-CT, a three-point bending assay, and Fourier Transform Infrared (FTIR) Spectrometry. The expressions of Calbindin D28K and Calcium-sensing receptor (CaSR) in kidney as well as the Vitamin D receptor (VDR), the transient receptor potential vanilloid receptor 6 (TRPV6), Calbindin D9k in the duodenum were measured by immunohistochemistry, western blotting, or real-time PCR. The short-chain fatty acids (SCFAs) levels in the feces of the cecum were tested by gas chromatograghy. RESULTS: The administration of FLL to OVX rats resulted in a significant improvement in bone mineral density and biomechanical strength as well as in maintaining bone microstructures and material quality. Meanwhile, the decreased levels of PINP and increased levels of CTx-I in OVX rats were restored by FLL treatment. Additionally, FLL treatment increased calcium absorption, upregulated VDR, TRPV6, Calbindin D9k expressions in the duodenum, Calbindin D28K in kidney, and down-regulated CaSR expression in the kidney, as well as enhanced SCFAs levels in the feces of OVX rats. CONCLUSIONS: FLL aqueous extract may preserve bone quality through regulation of the calcium balance and intestinal SCFAs production in OVX rats. This offers translational value of FLL into osteoporosis clinical trial.

Combined effects of different sizes of ZnO and ZIF-8 nanoparticles co-exposure with Cd2+ on HepG2 cells.

Heavy metal and nanoparticles (NPs) emitted in the environment have attracted worldwide attention. But the combined effect of NPs and heavy metals is still unclear. In this study, the combined effect of zinc-based NPs and Cd2+ on HepG2 cells was investigated by combining biological indicator detection methods with time-resolved inductively coupled plasma mass spectrometry (TRA-ICP-MS) single cell analysis, and the combined effect of Zn2+ and Cd2+ was also investigated for a comparison. High-dose of ZnO or ZIF-8 NPs co-exposure with Cd2+ would reduce the cell viability while low-dose of ZnO or ZIF-8 NPs co-exposure with Cd2+showed antagonism and the particle size has no remarkable effect on the combined toxicity. In the antagonism, Zn2+ would increase cellular Zn amount through increasing the expression of ZIP8 and ZIP14 transporters to manage the ROS generation, but the zinc-based NPs would decrease expression of these transporters to decrease cellular Cd amount to help maintain the cell viability. Thus, we should hold a dialectical thinking about the pollution of NPs emissions in the environment.

Analysis of Main Components in Jujube and Mulberry Extracts by High-Sensitive HPLC-ESI-Q-TOF-MS/MS.

In order to comprehensively reflect the cigarette quality, a method combining direct injection of diluted sample with high sensitive high-performance liquid chromatography (HPLC)- electrospray (ESI)- quadrupole (Q)- time of flight (TOF)- tandem mass spectrometry (MS/MS) was developed for the identification of major components of cigarette essences (jujube and mulberry extracts). Based on the observed relative molecular mass, MS/MS fragmentation behavior, MS/MS database and related literatures, the components of the jujube extract and mulberry extract were identified. The result shows that the composition of jujube extract and mulberry extract has some similarity. They all mainly contain amino acids, free amino compounds and Maillard reaction products, which are the main constituents of a cigarette essence.

Controlled Synthesis and Surface Engineering of Janus Chitosan-Gold Nanoparticles for Photoacoustic Imaging-Guided Synergistic Gene/Photothermal Therapy.

The unsymmetrical morphology and unique properties of Janus nanoparticles (JNPs) provide superior performances for biomedical applications. In this work, a general and facile strategy is developed to construct a series of symmetrical and unsymmetrical chitosan/gold nanoparticles. Taking advantage of the active motion derived from Janus structure, selective surface functionalization of polysaccharide domain, and photothermal effect of gold nanorods, Janus chitosan/gold nanoparticles (J-Au-CS) are selected as a model system to construct Janus-structured chitosan/gold nanohybrids (J-ACP). Near-infrared (NIR)-responsive J-ACP composed of polycationic chitosan nanospheres and PEGylated gold nanorods hold great potential to realize photoacoustic (PA) imaging-guided complementary photothermal therapy (PTT)/gene therapy for breast cancer. The morphology effect of chitosan/gold nanostructures on enhanced PTT, cellular uptake, and gene transfection is investigated. The feasibility of PA imaging to track the accumulation of J-ACP and guide PTT is also explored. Notably, synergistic therapy is achieved based on PTT-enhanced gene therapy. In addition, the loading function of chitosan/gold nanoparticles for fluorescence imaging is demonstrated. The current work extends the application of JNPs for imaging-guided synergistic cancer therapy and provides flexible candidates with distinct structures for diverse biomedical applications.

BaZiBuShen alleviates altered testicular morphology and spermatogenesis and modulates Sirt6/P53 and Sirt6/NF-κB pathways in aging mice induced by D-galactose and NaNO2.

ETHNOPHARMACOLOGICAL RELEVANCE: Sperm infertility and testicular atrophy are symptoms associated with aging. BaZiBuShen formula (BZBS), a patented Chinese herbal prescription composed of Semen Cuscutae, Fructus Lycii, Epimedii Folium, Fructus Schisandrae Sphenantherae, Fructus Cnidii, Fructus Rosae Laevigatae, Semen Allii Tuberosi., Radix Morindae Officinalis, Herba Cistanches, Fructus Rubi, Radix Rehmanniae Recens, Radix Cyathulae, Radix Ginseng, Cervi Cornu Pantotrichum, Hippocampus, and Fuctus Toosendan, has been used as a kidney-tonifying and anti-aging drug as well as for the treatment of impotence and male infertility in traditional Chinese medicine. AIM OF THE STUDY: We aimed at investigating whether BZBS preserves sperm and testes morphology in aging mice, and to explore the underlying mechanisms. MATERIALS AND METHODS: BZBS was orally administered to aging mice induced by D-galactose (D-gal) and NaNO2 for 65 days. Sperm quality and testes pathophysiological alterations were examined by a Semen Analysis System, hematoxylin-eosin staining, transmission electron microscopy, and mitochondrial complex IV activity. In addition, serum levels of total antioxidant capacity (TAC), malondialdehyde (MDA), 8-hydroxy-desoxyguanosine (8-OH-dG), reduced glutathione (GSH), oxidized glutathione disulfide (GSSG), testosterone (T), follicle stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2) and tumor necrosis factor-α (TNF-α) were determined by ELISA. The expressions of P450 aromatase (CYP19), sirtuin 6 (Sirt6), P53, inducible nitric oxide synthase (iNOS), nuclear factor-kappa B (NF-κB)-p65, and phospho-NF-κB-p65 (NF-κB-pp65) in the testes were examined by western blot and/or immunohistochemical staining. RESULTS: Sustained exposure to D-gal/NaNO2 caused a deterioration of sperm quality and testes morphology in this rapid aging mouse model. BZBS treatment curtailed these alterations. These beneficial effects were associated with increased serum levels of TAC, GSH/GSSG, T, E2, and FSH, and decreased levels of MDA, TNF-α, and 8-OH-dG. BZBS treatment also downregulated the expressions of P53, iNOS, and NF-κB-pp65, as well as upregulated the expressions of Sirt6 and CYP19 in aging testes. CONCLUSIONS: BZBS preserves testicular morphology and spermatogenesis possibly via inhibition of oxidative stress and the modulation of the Sirt6/P53 and Sirt6/NF-κB signaling pathways. The results shed light on the beneficial effect of BZBS on sperm quality and fertility in aging males.

Fructus Ligustri Lucidi preserves bone quality through induction of canonical Wnt/ß-catenin signaling pathway in ovariectomized rats.

Fructus Ligustri Lucidi (FLL) has been preclinically and clinically used to treat musculoskeletal diseases. However, whether and how FLL affect the canonical Wnt/ß-catenin signaling in the management of osteoporosis remains largely unknown. To this end, ovariectomized (OVX) rats and primary osteoblasts were administrated with FLL aqueous extract and medicated serum, respectively. Supplement of FLL to OVX rats maintains bone quality by attenuating the reduction in bone mineral density, strength and microstructure. The maintenance may be associated with upregulating the expression of insulin-like growth factor-1, osteoprotegerin, phospho (p)-low-density lipoprotein receptor-related protein 6, p-glycogen synthase kinase 3 beta (GSK3ß), ß-catenin, Runx2 and c-Myc, and downregulating the expressions of sclerostin (SOST), dickkopf-related protein 1 (DKK1), GSK3ß and p-ß-catenin in rat femurs and tibias. In addition, the medicated serum promotes osteoblastic bone formation through activation of Wnt/ß-catenin signaling via inhibition of DKK1 and SOST overexpression. Salidroside may be one of the active ingredients in FLL that are beneficial for bone homeostasis. In summary, our results suggest that FLL may preserve bone quality through induction of canonical Wnt/ß-catenin signaling via inhibition of DKK1 and SOST overexpression. And FLL may offer a new source of the DKK1 or SOST inhibitors in protection against osteoporosis.

Flexible Photothermal Assemblies with Tunable Gold Patterns for Improved Imaging-Guided Synergistic Therapy.

Self-assembly of gold nanoparticles demonstrates a promising approach to realize enhanced photoacoustic imaging (PAI) and photothermal therapy (PTT) for accurate diagnosis and efficient cancer therapy. Herein, unique photothermal assemblies with tunable patterns of gold nanoparticles (including arcs, rings, ribbons, and vesicles) on poly(lactic-co-glycolic acid) (PLGA) spheres are constructed taking advantage of emulsion-confined and polymer-directed self-assembly strategies. The influencing factors and formation mechanism to produce the assemblies are investigated in details. Both the emulsion structure and migration behaviors of amphiphilic block copolymer tethered gold nanoparticles are found to contribute to the formation of versatile photothermal assemblies. Hyaluronic acid-modified R-PLGA-Au (RPA) exhibits outstanding photothermal performances under NIR laser irradiation, which is induced by strong plasmonic coupling between adjacent gold nanoparticles. It is interesting that secondary assembly of RPA can be triggered by NIR laser irradiation. Prolonged residence time in tumors is achieved after RPA assemblies are fused into superstructures with larger sizes, realizing real-time monitoring of the therapeutic processes via PAI with enhanced photoacoustic signals. Notably, synergistic effect resulting from PTT-enhanced chemotherapy is realized to demonstrate high antitumor performance. This work provides a facile strategy to construct flexible photothermal assemblies with favorable properties for imaging-guided synergistic therapy.

Radix Stephaniae Tetrandrine: An Emerging Role for Management of Breast Cancer.

BACKGROUND: Radix Stephaniae Tetrandrine (RST), known as FangJi (Pinyin name) in Chinese, is the dried root of Stephania tetrandra S.Moore, and has been prescribed in combination with other herbs to treat cardiovascular diseases and breast cancer in traditional Chinese medicine (TCM) clinical trials. OBJECTIVE: The aim of the review is to provide a comprehensive evaluation about the application of RST in breast cancer management in TCM clinical trials, its ingredients, and its action on preventing the development of breast cancer in vitro and in vivo studies. METHODS: Literature sources used were Pubmed, CNKI.net, Cqvip.com, and the Web of Science. For the inquiry, keywords such as Fangji, breast cancer, clinical trials, Radix Stephaniae Tetrandrine, tetrandrine, and fangchinoline were used in various combinations. About 150 research papers and reviews were consulted. RESULTS: In TCM, RST exhibited the anti-tumor ability through its action on the bladder and lungs through dispersing phlegm and blood stasis. 10 clinical trials were identified which used RST in combination with other herbs to treat breast cancer. On average, the trials were characterized by high efficacy (>85%) and low toxicity. However, most of the clinical trials are characterized as small patient samples, poor design, and different combinations of herbs in prescriptions. To date, more and more compounds have been isolated from this plant. RST exhibited anti-tumor activities by targeting reversing multidrug resistance, inhibiting cell proliferation, inducing apoptosis, preventing tumor angiogenesis, anti-oxidation, anti-inflammation, and enhancing the sensitization and attenuating the toxicity of radiotherapy. CONCLUSION: The successful applications of RST in TCM clinical trials and preclinical experiments to beating breast cancer will provide potent lead compounds in the identification of novel anti-cancer drugs, which further contributes to the scientific exploration of functions of RST in TCM.

Fructus Ligustri Lucidi preserves bone quality through the regulation of gut microbiota diversity, oxidative stress, TMAO and Sirt6 levels in aging mice.

Gut dysbiosis and oxidative stress may trigger senile osteoporosis. Fructus Ligustri Lucidi (FLL) has bone-preserving properties and affects the intestinal microecology. However, the mechanism of the anti-osteoporotic effect of FLL and its link to the gut microbiota remains to be elucidated. Here, we demonstrated that sustained exposure of ICR mice to D-galactose / sodium nitrite for 90 days causes aging-related osteoporosis and reduced cognitive performance. The aging phenotype is also characterized by increased oxidative stress in serum. This is likely triggered by abnormal changes in the gut microbiota population of Bifidobacterium and the ratio of Firmicutes/ Bacteroidetes that resulted in increased levels of flavin-containing monooxygenase-3 and trimethylamine-N-oxide (TMAO). Moreover, the increased oxidative stress further accelerated aging by increasing tumor necrosis factor-α levels in serum and reducing Sirtuin 6 (Sirt6) expression in long bones, which prompted nuclear factor kappa-B acetylation as well as over-expression and activation of cathepsin K. FLL-treated aging mice revealed a non-osteoporotic bone phenotype and an improvement on the cognitive function. The mechanism underlying these effects may be linked to the regulation of gut microbiota diversity, antioxidant activity, and the levels of TMAO and Sirt6. FLL may represent a potential source for identifying anti-senile osteoporotic drug candidates.

Integration of sub-organ quantitative imaging LA-ICP-MS and fractionation reveals differences in translocation and transformation of CeO2 and Ce3+ in mice.

Information on the risk of exposure to cerium oxide (CeO2) nanoparticles (NPs) is limited. To assess risk, we must know where and how such NPs are distributed to the body after exposure, both short- and long-term. In this work, an integrated approach of quantitative LA-ICP-MS bioimaging and fractionation was employed to study the translocation and transformation of CeO2 and Ce3+ in mouse spleen and liver. The complementary information retrieved by the two techniques above on the accumulation of Ce and dissolution/aggregation were found consistent. In brief, a detailed fine scanning of a region of interest in the organ was performed after fast-screening at low spatial resolution. In the spleen, after short-term high-dose exposure, CeO2 NPs was found mainly in the marginal zone and caused an up-regulation of Zn in the white pulp. After long-term low-dose exposure, CeO2 was found in the marginal zone and white pulp. In the liver, CeO2 NPs were mainly distributed in the Kupffer cells and lobule periphery. The high spatial resolution LA maps of H&E-stained liver sections allowed imaging close to cell level; this enabled an estimation of Ce content in Kupffer cells. Furthermore, fractionation by ultrafiltration was also employed to differentiate the ionic and NP species in the organs. This fractionation showed aggregation of Ce ions in spleen, supporting the LA-ICP-MS results. Transmission electron microscopy revealed that long-term CeO2 exposure triggered an immune response to infection in the spleen and confirmed the differential deposition of Ce in the marginal zone. The integrated analyses based on ICP-MS together with histology and TEM investigation suggests that long-term low doses of CeO2 NPs may cause toxicity in the liver and impair functions of the immune system.

Salvia miltiorrhiza in diabetes: A review of its pharmacology, phytochemistry, and safety.

BACKGROUND: Salvia miltiorrhiza (SM), one of the frequently used herbs in traditional Chinese medicine (TCM), has now attracted rising interests for a possible alternative in the management of diabetes. This review is aimed to providing a comprehensive perspective of SM in phytochemical constituents, pharmacological activities against diabetes and its complications, and safety. METHODS: A comprehensive search of published literatures was conducted to locate original publications pertaining to SM and diabetes till the end of 2017 using PubMed, China National Knowledge Infrastructure, National Science and Technology Library, China Science and Technology Journal Database, and Web of Science database. The main inquiry was used for the presence of the following keywords in various combinations in the titles and abstracts: Salvia miltiorrhiza, diabetes, obesity, phytochemistry, pharmacology, and safety. About 200 research papers and reviews were consulted. RESULTS: SM exhibited anti-diabetic activities by treating macro- and micro-vascular diseases in preclinical experiments and clinical trials through an improvement of redox homeostasis and inhibition of apoptosis and inflammation via the regulation of Wnt/ß-catenin, TSP-1/TGF-ß1/STAT3, JNK/PI3K/Akt, kinin B2 receptor-Akt-GSK-3ß, AMPKß/PGC-1α/Sirt3, Akt/AMPK, TXNIP/NLRP3, TGF-ß1/NF-κB, mineralocorticoid receptor/Na+/K+-ATPase, AGEs/RAGE, Nrf2/Keap1, CaMKKß/AMPK, AMPK/ACC, IRS-1/PI3K signaling pathways, and modulation of K+-Ca2+ channels, as well as influence of VEGF, NOS, AGEs, PPAR expression and hIAPP aggregation. The antidiabetic effects of this herb may be related to its TCM characters of improving blood circulation and reliving blood stasis. The main ingredients of SM included salvianolic acids and diterpenoid tanshinones, which have been well studied in the diabetic animals. Acute and subacute toxicity studies supported the notion that SM is well tolerated. CONCLUSION: SM may offer a new strategy for prevention and treatment of diabetes and its complications that stimulates extensive research into identifying potential anti-diabetic compounds and fractions as well as exploring the underlying mechanisms of this herb. Further scientific evidences are still required from well-designed preclinical experiments and clinical trials on its anti-diabetic effects and safety.

Dihydromyricetin Inhibits α-Synuclein Aggregation, Disrupts Preformed Fibrils, and Protects Neuronal Cells in Culture against Amyloid-Induced Cytotoxicity.

Fibrillogenesis of α-synuclein (αSN) is associated with the onset and progression of Parkinson's disease (PD). Dihydromyricetin (DHM), a natural flavonoid compound extracted from Ampelopsis grossedentata, has proven antioxidative, antineuroinflammatory, and neuroprotective effects in dementia. However, it remains unclear if DHM can impede αSN fibrillogenesis and attenuate the corresponding cytotoxicity. Herein, we found that DHM could inhibit αSN fibrillogenesis and destabilize mature αSN fibrils in a dose-dependent manner. Moreover, DHM protected against αSN-induced cytotoxicity by improving the cell viability by 34.73 ± 3.68% at a 1:1 molar ratio of αSN to DHM. Molecular dynamics simulations showed that DHM interacts with the αSN trimer mainly via nonpolar mechanisms. The key residues by which αSN interacts with DHM were hydrophobic, and their side chains and main chains showed a synergistic effect via hydrophobic and hydrogen-bonding interactions. These findings suggest that DHM possesses great potential to be developed into a new aggregation inhibitor for αSN.

Radix Salviae miltiorrhizae improves bone microstructure and strength through Wnt/ß-catenin and osteoprotegerin/receptor activator for nuclear factor-κB ligand/cathepsin K signaling in ovariectomized rats.

Although radix Salviae miltiorrhizae (RSM) is reported to exhibit the antiosteoporotic effect in preclinical study, the underlying mechanism is unclear. To this end, ovariectomized (OVX) rats were employed with administration of RSM (5 g/kg) for 14 weeks. The disturbed serum levels of alkaline phosphatase (ALP), osteoprotegerin (OPG), tartrate-resistant acid phosphatase, and receptor activator of nuclear factor-κB ligand (RANKL) in OVX rats were improved by RSM treatment. Furthermore, supplement of RSM to OVX rats resulted in an increase in femoral bone mineral density and bone strength as well as an improvement in bone microstructures. Moreover, the decreased expression of phosphor (p)-LRP6, insulin-like growth factor-1(IGF-1), ALP, and OPG, as well as increased expression of RANKL and cathepsin K in the tibias and femurs of OVX rats were shifted by RSM treatment. Additionally, RSM reversed the decreased ratio of p-glycogen synthase kinase 3ß (GSK3ß) to GSK3ß and increased ratio of p-ß-catenin to ß-catenin in OVX rats. Altogether, it is suggestive that RSM improves bone quantity and quality by favoring Wnt/ß-catenin and OPG/RANKL/cathepsin K signaling pathways in OVX rats thereby suggesting the potential of this herb to be a novel source of antiosteoporosis drugs.