A Real-World Study on Safety and Efficacy of TAF Treatment in HBV Patients with High Risk of Osteoporosis or Osteopenia in China.

Objective: Long-term antiviral treatment is necessary for chronic hepatitis B (CHB) patients, and treatment safety is imperative for these patients. Previous studies showed tenofovir alafenamide (TAF) has shown efficacy non-inferior to that of tenofovir disoproxil fumarate (TDF) with improved renal and bone safety. However, there is still a lack of a rapid and convenient method to identify CHB patients at high risk of osteoporosis before initiating antiviral treatment. The International Osteoporosis Foundation (IOF) recommended a one-minute osteoporosis risk test to identify early high-risk patients. Our aim was to evaluate the feasibility of the one-minute osteoporosis risk test, along with evaluating the effectiveness and safety for virologically suppressed CHB patients switching to TAF. Methods: In this multicenter, prospective study, patients with chronic HBV infection who had been receiving TDF or Entecavir (ETV) for 48 weeks or more with HBV DNA less than 20 IU/mL for longer than 6 months were screened by one-minute osteoporosis risk test. Patients with a high risk of osteoporosis and then diagnosed with osteopenia or osteoporosis by dual-energy X-ray absorptiometry (DEXA) were enrolled. Safety in bone and bone turnover markers and antiviral efficacy of TAF were assessed respectively at 24 and 48 weeks. Results: 84.95% (175/206) CHB patients screened by one-minute osteoporosis risk test were at risk of osteoporosis.85.71% (150/175) were diagnosed with osteopenia by DEXA. The analysis included a total of 138 patients, of whom 92(62.3%) were male and 46 (37.7%) were female, with a mean age of 45 years old. HBV DNA was suppressed at 48 weeks at 88% (35/40) in the prior ETV group and 90% (88/98) at 48 weeks group in the prior TDF group. Bone mineral density (BMD) of the lumbar spine (L1-L4) from TDF switching to TAF was improved at 24 weeks (1.03±0.11 vs. 0.97±0.12, P = .001) than baseline. Propeptides of type I procollagen (PINP) and beta-C-terminal telopeptides of type 1 collagen (CTX) in serum at 24 weeks after switching from TDF to TAF declined compared with baseline (50.35±18.90 vs. 63.65±19.17, P = .016 and 0.21±0.13 vs. 0.32±0.10, P = .017). BMD, PINP, and CTX in ETV to TAF group remained stable during treatment. Conclusion: Attention should be paid to osteoporosis risk during lone-term nucleot(s)ide analogue treatment. One minute test of osteoporosis risk could rapidly identify most CHB patients at risk of osteoporosis. Given its convenience, we recommend using this test for early screening in CHB patients prior to initiating antiviral treatment. Our results further demonstrated that an improvement in bone safety after switching to TAF in virologically suppressed CHB patients with osteoporosis.

Enhancing the Quality of Life for Peritoneal Dialysis Patients: A Study of Influencing Factors.

Objective: The objective of this study was to examine the quality of life among peritoneal dialysis (PD) patients and identify the influencing factors. Methods: The study was conducted between March 2021 and December 2021 at the Peritoneal Dialysis Center of the Second Hospital affiliated with Harbin Medical University. A total of 148 patients with end-stage renal disease (ESRD) undergoing PD were included. Demographic information, assessments of dialysis adequacy, biochemical evaluations, and the administration of the Self-Rating Anxiety Scale (SAS) and Self-Rating Depression Scale (SDS) were carried out. The study analyzed the factors influencing the quality of life of these dialysis patients using the Spearman correlation coefficient and multiple linear regression. Results: The KDQOL-36 score for PD patients was 69.78±15.62, with 15.6% experiencing anxiety and 59.7% reporting depression. Age (r = -0.209), residual renal creatinine clearance rate (residual Ccr, r=-0.261), SAS (r=-0.623), and SDS (r = -0.116) scores exhibited significant negative correlations with KDQOL-36 scores (P < .05), while serum albumin levels (r = 0.199) showed significant positive correlations with KDQOL-36 scores (P < .05). Advanced age, poor nutritional status, low serum albumin levels, reduced residual renal Ccr, and high SAS and SDS scores were identified as significant predictors of lower KDQOL-36 scores (P < .05). Conclusions: The psychological state, age, nutritional status, serum albumin levels, and residual renal function significantly impacted the quality of life of PD patients.

Pectin alleviates the pulmonary inflammatory response induced by PM2.5 from a pig house by modulating intestinal microbiota.

This study aimed to investigate whether dietary fiber pectin can alleviate PM2.5-induced pulmonary inflammation and the potential mechanism. PM2.5 samples were collected from a nursery pig house. The mice were divided into three groups: the control group, PM2.5 group and PM2.5 + pectin group. The mice in the PM2.5 group were intratracheally instilled with PM2.5 suspension twice a week for four consecutive weeks, and those in the PM2.5 + pectin group were subject to the same PM2.5 exposure, but fed with a basal diet supplemented with 5% pectin. The results showed that body weight and feed intake were not different among the treatments (p > 0.05). However, supplementation with pectin relieved PM2.5-induced pulmonary inflammation, presenting as slightly restored lung morphology, decreased mRNA expression levels of IL-1ß, IL-6 and IL-17 in the lung, decreased MPO content in bronchoalveolar lavage fluid (BLAF), and even decreased protein levels of IL-1ß and IL-6 in the serum (p < 0.05). Dietary pectin altered the composition of the intestinal microbiota, increasing the relative abundance of Bacteroidetes and decreasing the ratio of Firmicutes/Bacteroidetes. At the genus level, short-chain fatty acid (SCFA)-producing bacteria, such as Bacteroides, Anaerotruncus, Prevotella 2, Parabacteroides, Ruminococcus 2 and Butyricimonas, were enriched in the PM2.5 +pectin group. Accordingly, dietary pectin increased the concentrations of SCFAs, including acetate, propionate, butyrate and valerate, in mice. In conclusion, dietary fermentable fiber pectin can relieve PM2.5-induced pulmonary inflammation via alteration of intestinal microbiota composition and SCFA production. This study provides a new insight into reducing the health risk associated with PM2.5 exposure.

Activity and potential mechanisms of action of persimmon tannins according to their structures: A review.

One distinguishing feature of the persimmon, that differentiates it from other fruits, is its high proanthocyanidins content, known as persimmon tannin (PT). Despite the poor absorption of PT in the small intestine, results from animal studies demonstrate that PT has many health benefits. Our goal in this review is to summarize the literature that elucidates the relationship between PT structure and activity. In addition, we also summarize the potential mechanisms underlying the health benefits that result from PT consumption; this includes the hypolipidemic, hypoglycemic, antioxidant, anti-inflammatory, antiradiation, antibacterial and antiviral, detoxification effects on snake venom, and the absorption of heavy metals and dyes. Studies show that PT is a structurally distinct proanthocyanidins that exhibits a high degree of polymerization. It is galloylation-rich and possesses unique A-type interflavan linkages in addition to the more common B-type interflavan bonds. Thus, PT is converted into oligomeric proanthocyanidins by depolymerization strategies, including the nucleophilic substitution reaction, acid hydrolysis, and hydrogenolysis. In addition, multiple health benefits exerted by PT mainly involve the inactivation of lipogenic and intracellular inflammatory signaling pathways, activation of the fatty acid oxidation signaling pathway, regulation of gut microbiota, and highly absorptive properties.

The relationship between gut microbiota and COVID-19 progression: new insights into immunopathogenesis and treatment.

The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has posed a global health crisis. Increasing evidence underlines the key role of competent immune responses in resisting SARS-CoV-2 infection and manifests the disastrous consequence of host immune dysregulation. Elucidating the mechanisms responsible for deregulated host immunity in COVID-19 may provide a theoretical basis for further research on new treatment modalities. Gut microbiota comprises trillions of microorganisms colonizing the human gastrointestinal tract and has a vital role in immune homeostasis and the gut-lung crosstalk. Particularly, SARS-CoV-2 infection can lead to the disruption of gut microbiota equilibrium, a condition called gut dysbiosis. Due to its regulatory effect on host immunity, gut microbiota has recently received considerable attention in the field of SARS-CoV-2 immunopathology. Imbalanced gut microbiota can fuel COVID-19 progression through production of bioactive metabolites, intestinal metabolism, enhancement of the cytokine storm, exaggeration of inflammation, regulation of adaptive immunity and other aspects. In this review, we provide an overview of the alterations in gut microbiota in COVID-19 patients, and their effects on individuals' susceptibility to viral infection and COVID-19 progression. Moreover, we summarize currently available data on the critical role of the bidirectional regulation between intestinal microbes and host immunity in SARS-CoV-2-induced pathology, and highlight the immunomodulatory mechanisms of gut microbiota contributing to COVID-19 pathogenesis. In addition, we discuss the therapeutic benefits and future perspectives of microbiota-targeted interventions including faecal microbiota transplantation (FMT), bacteriotherapy and traditional Chinese medicine (TCM) in COVID-19 treatment.

Aggregating in vitro-grown adipocytes to produce macroscale cell-cultured fat tissue with tunable lipid compositions for food applications.

We present a method of producing bulk cell-cultured fat tissue for food applications. Mass transport limitations (nutrients, oxygen, waste diffusion) of macroscale 3D tissue culture are circumvented by initially culturing murine or porcine adipocytes in 2D, after which bulk fat tissue is produced by mechanically harvesting and aggregating the lipid-filled adipocytes into 3D constructs using alginate or transglutaminase binders. The 3D fat tissues were visually similar to fat tissue harvested from animals, with matching textures based on uniaxial compression tests. The mechanical properties of cultured fat tissues were based on binder choice and concentration, and changes in the fatty acid compositions of cellular triacylglyceride and phospholipids were observed after lipid supplementation (soybean oil) during in vitro culture. This approach of aggregating individual adipocytes into a bulk 3D tissue provides a scalable and versatile strategy to produce cultured fat tissue for food-related applications, thereby addressing a key obstacle in cultivated meat production.

Clinical Significance of Neuregulin 4, Afamin, and SERPINB1 in Gestational Diabetes Mellitus and Their Relationship with Insulin Resistance.

Objective: This study aims to explore the serum levels of neuregulin 4 (NRG4), afamin (AFM), and serpin family B member 1 (SERPINB1) in gestational diabetes mellitus (GDM) patients and their relationship with insulin resistance. Method: Serum levels of AFM, SERPINB1, and NRG4 were measured in GDM (n = 58), and non-GDM women (n = 60) using enzyme-linked immunosorbent assay (ELISA) kits. Besides, the serum insulin and glucose levels were also measured followed by calculating the homeostatic model assessment of insulin resistance (HOMA-IR). The correlation was performed using the Pearson analysis. Results: The increased serum levels of AFM and SERPINB1 were revealed in GDM patients as compared with non-GDM women, accompanied by the lower NRG4 serum level. ROCs for AFM concentrations showed an AUC of 0.629 (95% CI: 0.527∼0.731), 0.832 (95% CI: 0.754∼0.909) for the SERPINB1 serum level, and 0.626 (95% CI: 0.524∼0.728) for the NRG4 serum level. The threshold was 108.05 mg/L, 8.75 ng/mL, and 96.25 ng/mL of AFM, SERPINB1, and NRG4. Moreover, the combined ROC of AFM, SERPINB1, and NRG4 serum levels showed higher sensitivity (72.41%) and specificity (85.00%) for the diagnosis of GDM (AUC = 0.839; 95% CI: 0.764∼0.913). In GDM patients, the Pearson analysis revealed a significant correlation between AFM and SERPINB1 (r = 0.776), AFM and NRG4 (r = -0.799), as well as SERPINB1 and NRG4 (r = -0.783). Moreover, AFM and SERPINB1 serum concentrations in GDM patients were positively related to insulin levels, fasting glucose levels, and HOMA-IR values. However, the SERPINB1 serum level was negatively correlated with serum insulin and glucose levels and HOMA-IR. Conclusion: Abnormal serum levels of NRG4, AFM, and SERPINB1, as highly sensitive diagnostic tools, are closely related to insulin resistance in GDM patients.

Formation and characterization of starch-based spherulite: Effect of molecular weight of potato amylose starch.

Potato starch spherulites (PSS) with different molecular weights were obtained by controlled enzymatic hydrolysis of potato amylose starch, followed by super-heated quenching treatment. The impact of enzymatic hydrolysis on mean particle diameter and molecular weight was observed, ranging from 355 to 57 nm. Structural and physicochemical characteristics of produced spherulites were determined using scanning electron microscopy, X-ray diffraction, Fourier transform infrared spectroscopy, differential scanning calorimetry and rheological measurements. Rheological analysis indicated that PSS sample was viscoelastic with shear-thinning behavior. PSS was found to exhibit weak B-type crystallinity, similarly to that in native starch. PSS25% had a higher thermal stability with 128.5 °C melting temperature. Microstructure confirmed there were small spherulites (1-3 µm) formed with hydrolyzed amylose starch, and starch with 15% enzymatic-hydrolysis degree was more beneficial to develop spherulite. These results may be useful in development of starch-based functional ingredients applied in plant-based foods as fat replacers, structure formers, or delivery systems.

Fabrication of immobilized bromelain using cobalt phosphate material prepared in deep eutectic solvent as carrier.

The aim of the present work is to fabricate immobilized bromelain based on the specific interaction between the cobalt ions of carrier and the inherent cysteines contained in bromelain molecules. The cobalt phosphate material was prepared as solid support by using choline chloride (ChCl)/betaine-glycerol deep eutectic solvent (DES) as solvent and template for the first time. The Co-P material with lamellate-based structure obtained in the ChCl-glycerol DES at the Co/P ratio of 3:2 showed the best performance for the immobilization of bromelain. The specific interaction between Co2+ and bromelain promoted the aggregation of lamellar Co-P, forming flower-like Co-P@bromelain particles. Under the optimum immobilization conditions, the specific enzyme activity of the immobilized enzyme reached the maximum of 71244 U/g. Compared with Co3(PO4)2 prepared in water system, the obtained Co-P@bromelain using the Co-P material synthesized in the ChCl-glycerol DES as carrier exhibited excellent structure stability. In addition, the immobilized Co-P@bromelain also showed higher catalytic efficiency than free bromelain.

Insights into spatiotemporal variations of the water quality in Taihu Lake Basin, China.

Taihu Lake Basin is highly developed but suffers from perennial water shortages due to pollution. Most studies have been limited to examining the water quality in specific areas, but few have investigated the entire basin. This study was based on official water quality data obtained from 565 sites in the monitoring network, thereby covering the entire basin. The water quality spatiotemporal variations were explored by statistical analysis, and the precise spatial distribution of the main pollutants was analyzed by heat maps. Only 29.09% of the water quality assessment results showed "drinkable," whereas 28.63% showed "moderate" and "severe" pollution. The "severe" proportion had a significant declining trend (R2 = 0.933) and was affected by the variations of nitrogen that was related to rainfall and anthropogenic activities. The water quality spatial variation was most likely related to anthropogenic influence and land use. The water quality in the developed and densely populated urban areas was poor, especially in downtown Shanghai. NH3-N, TN, TP, BOD5, COD, CODMn, and DO were the main pollutants that affected the water quality. NH3-N and TN were major reduction targets. NH3-N was the main pollutant that deteriorated the water quality in most densely populated urban areas. Many lakes and reservoirs were highly polluted with TN. Controlling domestic sewage may be effective to improve the water quality. This study makes up for the limited research on the water quality spatiotemporal variations in the entire Taihu Lake Basin and provides beneficial information and suggestions for decision-making regarding the water management.

Toxicological evaluation of S. involucrata culture: Acute, 90-day subchronic and genotoxicity studies.

Saussurea involucrata is an endangered plant that is used in traditional Chinese medicine. Through the use of plant cell culture techniques, preparations of Saussurea involucrata (S. involucrata) cell cultures have been developed and used to generate medicinal preparations. There have been few evidence-based analyses of the toxicological effects of S. involucrata culture conducted to date. Here, we conducted the experiments designed to assess the acute, subchronic, and genotoxic toxicological effects of S. involucrata culture. The genotoxic study was assessed through Ames, marrow micronucleus, and sperm malformation assays. The acute toxicity was assessed by orally administering in rats and mice at dose of 7500 mg/kg. Subchronic toxicity studies were then conducted by administering rats at doses of 500, 1000, or 1500 mg/kg for 90 days. No genotoxicity was observed at any tested dose levels, nor was any evidence of acute toxicity detected in treated mice or rats. Similarly, subchronic study of S. involucrata culture administration was not associated with any changes in rat food intake, weight, hematological parameters, organ weight, or organ histology. Then, we determined that the no observed adverse effect level of S. involucrata culture was greater than 1500 mg/kg in our 90-day toxicity study.

Scutellaria baicalensis extract and baicalein inhibit replication of SARS-CoV-2 and its 3C-like protease in vitro.

COVID-19 has become a global pandemic and there is an urgent call for developing drugs against the virus (SARS-CoV-2). The 3C-like protease (3CLpro) of SARS-CoV-2 is a preferred target for broad spectrum anti-coronavirus drug discovery. We studied the anti-SARS-CoV-2 activity of S. baicalensis and its ingredients. We found that the ethanol extract of S. baicalensis and its major component, baicalein, inhibit SARS-CoV-2 3CLpro activity in vitro with IC50's of 8.52 µg/ml and 0.39 µM, respectively. Both of them inhibit the replication of SARS-CoV-2 in Vero cells with EC50's of 0.74 µg/ml and 2.9 µM, respectively. While baicalein is mainly active at the viral post-entry stage, the ethanol extract also inhibits viral entry. We further identified four baicalein analogues from other herbs that inhibit SARS-CoV-2 3CLpro activity at µM concentration. All the active compounds and the S. baicalensis extract also inhibit the SARS-CoV 3CLpro, demonstrating their potential as broad-spectrum anti-coronavirus drugs.

Multiple co-pigments of quercetin and chlorogenic acid blends intensify the color of mulberry anthocyanins: insights from hyperchromicity, kinetics, and molecular modeling investigations.

BACKGROUND: The effect of multiple co-pigments on the color intensification of mulberry anthocyanins (ACs) using spectroscopic techniques in combination with a molecular docking study was studied. The hyperchromicity of ACs co-pigmented with chlorogenic acid (CH) and quercetin (Q) blends was measured and their color stability in liquid and encapsulated particle models was evaluated. RESULTS: Multiple co-pigments exhibited higher hyperchromicity, pKH -values, and heat-stability than their individual counterparts. Surflex-docking findings confirmed that stronger binding occurred between multiple ligands and AC than single ones due to their extra -OH, -COOH groups, and delocalization systems. The binding was allowed by increased H-bonding, van der Waals forces, and π-π sites by the extra groups of the multiple co-pigments with AC in aqueous juice and whey particle-based models. CONCLUSION: This is the first report of the ternary mixture of phenolic acid-flavonol-anthocyanin which could be used as promising food red-colorants. © 2020 Society of Chemical Industry.

Ancient genomes reveal tropical bovid species in the Tibetan Plateau contributed to the prevalence of hunting game until the late Neolithic.

Local wild bovids have been determined to be important prey on the northeastern Tibetan Plateau (NETP), where hunting game was a major subsistence strategy until the late Neolithic, when farming lifestyles dominated in the neighboring Loess Plateau. However, the species affiliation and population ecology of these prehistoric wild bovids in the prehistoric NETP remain unknown. Ancient DNA (aDNA) analysis is highly informative in decoding this puzzle. Here, we applied aDNA analysis to fragmented bovid and rhinoceros specimens dating ∼5,200 y B.P. from the Neolithic site of Shannashuzha located in the marginal area of the NETP. Utilizing both whole genomes and mitochondrial DNA, our results demonstrate that the range of the present-day tropical gaur (Bos gaurus) extended as far north as the margins of the NETP during the late Neolithic from ∼29°N to ∼34°N. Furthermore, comparative analysis with zooarchaeological and paleoclimatic evidence indicated that a high summer temperature in the late Neolithic might have facilitated the northward expansion of tropical animals (at least gaur and Sumatran-like rhinoceros) to the NETP. This enriched the diversity of wildlife, thus providing abundant hunting resources for humans and facilitating the exploration of the Tibetan Plateau as one of the last habitats for hunting game in East Asia.

A 26-week toxicological study of Xuezhikang (XZK), red yeast rice extract, in Beagle dogs with a 4-week recovery period.

Xuezhikang (XZK) is an extract derived from red yeast rice that is commonly used to treat cardiovascular conditions as a traditional Chinese medicine, both within China and globally. Genotoxicity, acute toxicity, and a 26-week toxicity study in rat have been reported in our previous publication. The present study was designed to assess the long-term safety of XZK when administered orally to dogs. Dogs were treated with encapsulated XZK at a maximum dose of 2000 mg/kg followed by 1000 mg/kg and 500 mg/kg (n = 6/sex/group) for this 26-week oral toxicity study. Control animals were given an empty capsule. Treated animals were then monitored through measurements of body weight, body temperature, food intake, ophthalmic and electrocardiogram examinations, general clinical observations, mortality rates, and clinical and anatomic pathological findings. Additionally, blood samples were collected and used to conduct hematological and biochemical analysis. Several abnormalities were found in all groups including: fecal abnormalities (including mucoid, poorly formed, or liquid feces). Moreover, reduced CHOL and TRIG values were seen in all XZK groups (p < 0.05), increased WBC and NEUT levels in 500 mg/kg group (males only, p < 0.05), and elevated AST, ALT, and ALP activities in 2000 mg/kg group (p < 0.05). These changes were resolved in the recovery period. The results indicated that XZK may temporarily impact the liver enzyme levels, but were not considered adverse effects. These findings yielded a NOAEL for XZK in dogs of 2000 mg/kg.

L-Arginine alleviates the testosterone reduction in heat-treated mice by upregulating LH secretion, the testicular antioxidant system and expression of steroidogenesis-related genes.

High temperature can reduce testes function, leading to decreased testosterone secretion. Dietary l-arginine (l-Arg) supplementation improves the semen quality and libido of boars. The present study investigated whether l-Arg could enhance the production of testosterone in mice exposed to high ambient temperature. Twenty-four 6-week-old male ICR mice were randomly divided into three groups: a control group, a heat-treated (HT) group and a group subjected to heat treatment plus 2mg kg-1 l-Arg (HT+Arg). l-Arg was administered to mice by oral gavage for 18 consecutive days, after which the HT and HT+Arg groups were placed into an incubator at 40°C for 30min every day for 5 days. Serum testosterone and LH concentrations were significantly increased in the HT+Arg compared with HT group, as was catalase, total superoxide dismutase and glutathione peroxidase activity and the expression of steroidogenesis-related genes steroidogenic acute regulatory protein (Star), steroidogenic factor-1 (Sf1), 17ß-hydroxysteroid dehydrogenase 3 (Hsd17b3) and 17α-hydroxylase/17,20-lyase (Cyp17a1) in the testes. These results demonstrate that l-Arg can alleviate testosterone reductions in heat-treated mice by upregulating LH secretion, enhancing the antioxidant system and increasing the expression of testosterone synthesis-related genes.

Therapeutic effect of Xuebijing combined with thymosin on hemorrhagic fever with renal syndrome: A protocol of systematic review and meta-analysis.

BACKGROUND: The goal of this study is to assess the therapeutic effect of Xuebijing combined with thymosin (XBJ-T) for the treatment of patients with hemorrhagic fever with renal syndrome (HFRS). METHODS: We will search the electronic databases of Cochrane Library, PUBMED, EMBASE, PsycINFO, Scopus, Opengrey, Cumulative Index to Nursing and Allied Health Literature, Web of Science, Google scholar, Allied and Complementary Medicine Database, and Chinese Biomedical Literature Database from inception to the present. No language and publication status will be employed in this study. Based on the predefined eligibility criteria, selection of study and data extraction will be performed by 2 researchers independently. Study quality will be assessed using Cochrane risk of bias tool. We will apply RevMan 5.3 software to pool and analyze the extracted data. RESULTS: This study will assess the therapeutic effect of XBJ-T for the treatment of patients with HFRS. CONCLUSION: The findings of this study may provide systematic evidence to judge whether XBJ-T is an effective and safety intervention for HFRS. STUDY REGISTRATION NUMBER: INPLASY202040068.

Toxicological evaluation of, red rice yeast extract, Xuezhikang: Acute, 26-week chronic and genotoxicity studies.

Xuezhikang (XZK), an extract derived from red yeast rice, is commonly employed as a traditional Chinese medicine for treating coronary heart disease, improving endothelial function, decreasing blood lipids and preventing other cardiovascular events both within China and globally. However, there have not been studies of the toxicity associated with XZK. In this publication we hope to summarize and evaluate an acute study, a 26-week chronic toxicity study, and the genetic toxicity potential of XZK. Firstly, Sprague Dawley (SD) rats were treated with XZK at dose of 10 g/kg to observe the acute toxicity. Then, we sought to assess the toxicity of XZK (0, 500, 1000, and 2000 mg/kg) in SD rats for 26 weeks with a 4-week recovery period. Lastly, we assessed the genotoxicity of XZK utilizing an Ames test, chromosomal aberration assay, and mammalian micronucleus test. The results of the acute study, XZK did not induce toxicity up to the maximum doses of 10 g/kg in rats, so an LD50 could not be determined. In the chronic study, XZK administrated via gavage did not alter weight, food intake, urinalysis parameters, hematological analysis parameters, organ weight, organ to weight ratio, microscopic and macroscopic examination of organs. Also, we found no genotoxicity markers at any dose of XZK tested. The results revealed that the no observed adverse effect level (NOAEL) for XZK, based on the 26-week toxicity study, was 2000 mg/kg.

Chuanxiong (Rhizome of Ligusticum chuanxiong) Protects Ovariectomized Hyperlipidemic Rats from Bone Loss.

Oxidative stress (OS) is the common mechanism for age-related diseases. The co-occurrence of osteoporosis (OP) and cardiovascular disease (CVD) in postmenopausal women makes it warranted to find a holistic approach for treatment of multiple diseases or conditions. The rhizome of Ligusticum chuanxiong Hort. (CX), which has high anti-oxidant properties and is widely used for CVD treatment in China, might be the potential candidate. In the present study, CX ethanol extract (CXE) was applied to H2O2 induced MG63 cells to study its effects and mechanisms on osteoblastogenesis against OS. CXE was then administered to six-month-old Sprague Dawley sham or ovariectomized (OVX) rats fed either a low saturated fat-sucrose (LFS) or a high fat-sucrose (HFS) diet for 12 weeks, to confirm its anti-osteoporotic effects. The results demonstrated that CXE directly improved proliferation and differentiation in vitro in an H2O2-induced osteoblast cell model by attenuating cellular reactive oxygen species levels and inhibiting osteoblast apoptosis via PI3K/Akt signaling pathway. CXE significantly improved bone properties as revealed by the increase in trabecular bone mineral density and decrease in trabecular separation at proximal metaphysis of the tibia (PT) in HFS-fed OVX rats but not in LFS-fed OVX rats. CXE ameliorated dyslipidemia, greatly reduced lipid deposition and malondialdehyde levels, improved activities of superoxide dismutase, catalase and glutathione peroxidase in the livers of HFS-fed OVX rats. In conclusion, CXE could favor osteoblastogenesis against OS. The ability of CXE to reduce bone loss in HFS-fed OVX rats was associated with its abilities to correct dyslipidemia, and reduce lipid deposition and OS levels.

Manganese oxide doped carbon dots for temperature-responsive biosensing and target bioimaging.

We report on the synthesis of manganese oxide doped CDs (MnOx-CDs) by a hydrothermal strategy using manganese (III) acetylacetonate (Mn(III) (C5H7O2)3) as the only raw materials. The MnOx-CDs exhibit water solubility, favorable biocompatibility, low cytotoxicity, and show blue fluorescence with excitation/emission maxima at 326/442 nm with a quantum yield of 11.3%, allowing efficient cellular imaging. The MnOx-CDs have a reversible temperature-sensitive fluorescent property in vitro within 10-60 °C, which can also be used as a sensitive thermometer in living cells. By a scratch assay, the MnOx-CDs can restrain the migration of HepG2 cancer cells, which make the MnOx-CDs be attractive candidates for liver cancer adjuvant treatment. Besides, the fluorescence of the MnOx-CDs is quenched in the presence of Fe3+ due to the formation of a nonfluorescent MnOx-CDs-Fe3+ complex between oxygen-containing groups on the surface of MnOx-CDs and Fe3+, and the quenched fluorescence of MnOx-CDs can be turn-on by dissociation of MnOx-CDs-Fe3+ complexes by biothiols including L-cysteine, homocysteine and glutathione. Therefore, the Fe3+ and biothiols can be sequentially detected with high reliability and accuracy via exploiting the on-off-on nanosensor at room temperature, respectively. Further application to detection biothiols in human serum indicated that the probe was practicality and feasibility in medical field.