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The burgeoning availability of sensing technology and location-based data is driving the expansion of analysis of human mobility networks in science and engineering research, as well as in epidemic forecasting and mitigation, urban planning, traffic engineering, emergency response, and business development. However, studies employ datasets provided by different location-based data providers, and the extent to which the human mobility measures and results obtained from different datasets are comparable is not known. To address this gap, in this study, we examined three prominent location-based data sources—Spectus, X-Mode, and Veraset—to analyze human mobility networks across metropolitan areas at different scales: global, sub-structure, and microscopic. Dissimilar results were obtained from the three datasets, suggesting the sensitivity of network models and measures to datasets. This finding has important implications for building generalized theories of human mobility and urban dynamics based on different datasets. The findings also highlighted the need for ground-truthed human movement datasets to serve as the benchmark for testing the representativeness of human mobility datasets. Researchers and decision-makers across different fields of science and technology should recognize the sensitivity of human mobility results to dataset choice and develop procedures for ground-truthing the selected datasets in terms of representativeness of data points and transferability of results. • Analyzed human mobility networks across metropolitan areas at different scales: global, sub-structure, and microscopic with three prominent location-based data sources—Spectus, X-Mode, and Veraset. • Recognize the sensitivity of human mobility results to dataset choice and transferability of results and representativeness of human mobility datasets. [ABSTRACT FROM AUTHOR]

The nephrotoxicity and carcinogenicity induced by traditional Chinese medicines (TCMs) containing aristolochic acids (AAs) and related compound preparations have greatly limited their clinical application. While the toxicity of AA-I and AA-II is relatively clear, there are marked differences in the toxic effects of different types of aristolochic acid analogues (AAAs). Thus, the toxicity of TCMs containing AAAs cannot be evaluated based on the toxicity of a single compound. To systematically investigate the toxicity induced by Zhushalian (ZSL), Madouling (MDL) and Tianxianteng (TXT) as representative TCMs derived from Aristolochia. AAA contents in ZSL, MDL and TXT were determined using HPLC. Subsequently, mice were treated for 2 weeks with high (H) and low (L) dosages of TCMs containing total AAA contents of 3 mg/kg and 1.5 mg/kg, respectively. Toxicity was evaluated using biochemical and pathological examination and was based on organ indices. Correlations between AAA contents and induced toxicity were analysed using multiple methods. Of the total AAA content, ZSL contained mainly AA-I and AA-II (>90%, of which AA-I accounted for 49.55%). AA-I accounted for 35.45% in MDL. TXT mainly contained AA-IVa (76.84%) and other AAAs accounted for <10%. Short-term toxicity tests indicated that ZSL and high-dose MDL induced obvious renal interstitial fibrosis and gastric injury, whereas TXT (high and low dosages) caused only slight toxicity. Correlation analysis suggested that AA-I might be the critical hazard factor for toxicity. The toxicity of TCMs containing AAAs cannot be generalised. The toxicity of TXT is relatively low compared with those of ZSL and MDL. The toxicity of Aristolochia depends mainly on the AA-I content; therefore, control of AA-I levels in TCMs and related compound preparations is required to reduce the risk of toxicity associated with the use of Aristolochia herbs in clinical settings. [Display omitted] • Toxicity of herbs containing AAAs cannot be generalised. • Ranking of content of AA-I: ZSL > MDL > TXT. • Ranking of toxicity: ZSL > MDL > TXT. • Aristolochia herb toxicity depends mainly on the AA-I content. [ABSTRACT FROM AUTHOR]

[Display omitted] • Haematococcus pluvialis protein were prepared to stabilize Pickering emulsions. • Pickering emulsions based on HPP showed good stability and rheological properties. • HPP-stabilized Pickering emulsions displayed excellent antioxidant activity. • The emulsion nutritional microspheres were applied in traditional dumpling stuffing. In this study, the oil-in-water Pickering emulsions were prepared using Haematococcus Pluvialis protein (HPP) particles as an emulsifier by a simple one-step emulsification method. The internal oil phase was as high as 70 % due to the excellent emulsifying properties of HPP, and the average size of oil droplets in the emulsion was around 20 μm. The emulsion prepared by 2.5 % HPP with the oil phase ratio of 70 % showed the best stability after 14 days of storage, and the emulsion could maintain stability at acidic condition, high ionic strength, low and high temperatures. However, all emulsion samples exhibited shear thinning phenomenon, and the higher HPP concentration and oil phase ratio led to greater G′ and G″ modulus. NMR relaxation results showed that high concentration HPP could limit the mobility of free water in the emulsion and improve the emulsion stability. The HPP-stabilized emulsion could inhibit the oxidation of oil phase during storage due to the DPPH and ABTS radical scavenging activity of astaxanthin (AST) in HPP. Finally, the nutritional microspheres based on HPP-stabilized emulsion showed good stability in traditional dumplings and could reduce the loss of AST and DHA in algae oil during the boiling of dumplings. [ABSTRACT FROM AUTHOR]

Extracellular vesicles (EVs) are very attractive as carriers of active components due to their good immunological and their ability to penetrate the physiological barrier that synthetic delivery carriers cannot penetrate. However, the low secretion capacity of EVs limited its widespread adoption, let alone the lower yield of EVs loaded with active components. Here, we report a large-scale engineering preparation strategy of synthetic probiotic membrane vesicles for encapsulating fucoxanthin (FX-MVs), an intervention for colitis. Compared with the EVs naturally secreted by probiotics, the engineering membrane vesicles showed a 150-fold yield and richer protein. Moreover, FX-MVs improved the gastrointestinal stability of fucoxanthin and inhibited H 2 O 2 -induced oxidative damage by scavenging free radicals effectively (p < 0.05). The in vivo results showed that FX-MVs could promote the polarization of macrophages to M2 type, prevent the injury and shortening of colon tissue (p < 0.05), and improve the colonic inflammatory response. Consistently, proinflammatory cytokines were effectively suppressed after FX-MVs treatment (p < 0.05). Unexpectedly, such engineering FX-MVs could also reshape the gut microbiota communities and improve the abundance of short-chain fatty acids in the colon. This study lays a foundation for developing dietary interventions using natural foods to treat intestinal-related diseases. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Emerging clinical usage and pharmacological effects have been achieved in using Rehmanniae Radix either singly or in combination with other herbs to treat skeletal diseases in traditional Chinese medicine (TCM) in the recent years. This study is aimed to provide a comprehensive review about the historical TCM interpretation of the action of Rehmanniae Radix in osteoporosis, its usage in clinical trials and osteoporotic models, its main phytochemical constituents, and its pharmacokinetics. Materials and methods Several databases included PubMed, China Knowledge Resource Integrated Database, China Science and Technology Journal Database, National Science and Technology Library and the Web of Science Database were consulted to locate the publications pertaining to Rehmanniae Radix . The initial inquiry was conducted for the presence of the following terms combinations in the abstracts: Rehmanniae Radix , Dihuang, phytochemistry, pharmacokinetics, osteoporosis, bone, osteoclast and osteoblast. About 330 research papers and reviews were consulted. Results In TCM, Rehmanniae Radix exerts the anti-osteoporotic effect via regulating the functions of kidney and liver as well as improving blood circulation. 107 clinical trials are identified that used Rehmanniae Radix in combination with other herbs to treat post-menopausal, senile and secondary osteoporosis. Most of the clinical trials are characterized by high efficacy and no obvious adverse effects. However, the efficacies of these clinical trials are limited because of small patient sample size, short treatment duration and poor clinical design. In addition, TCM herbs under the clinical study are not clear because of a lack of standardization and authentication. The pharmacokinetics data demonstrate that the ingredients of Rehmanniae Radix are widely distributed after administration, and that catalpol and ajugol as well as acetoside are supposed to be the active constituents. More than 140 individual compounds have been currently isolated from this plant and reported to show pleiotropic effects on various diseases. Rehmanniae Radix displays bone protecting features in the osteoporosis models via the delicate balance between osteoclastogenesis and osteoblastogenesis through single herb extracts and its isolated compounds. Conclusions The successful inclusion of Rehmanniae Radix in clinical trials and preclinical studies for the management of osteoporosis has attracted rising attentions for identifying potential anti-osteoporotic candidates from this plant and clinical existing TCM formulas, which will further speed up anti-osteoporosis drug discovery processes. Properly designed and well controlled prospective studies are still needed to further demonstrate bone protective actions and safe use of this herb and its ingredients [ABSTRACT FROM AUTHOR]

Kudiezi injection (KDZI), also known as Diemailing injection, is a traditional Chinese medicine injection of the composite plant Ixeris sonchifolia Hance (also known as Kudiezi), and has been widely used to treat coronary heart disease, angina pectoris, and cerebral infarction, but its pharmacological mechanisms remain unclear. This study is designed to explore the effects of KDZI on middle cerebral artery occlusion and reperfusion (MCAO/R) rats, and to identify metabolic features of cerebral ischemia reperfusion by using a nontargeted metabolic profiling method based on ultra-performance liquid chromatography-high resolution mass spectrometry (UPLC-HRMS). In this process, 32 potential biomarkers were found in plasma. KDZI significantly upregulated the levels of taurochenodesoxycholic acid, leucine, l-phenylalanine, l-tryptophan, arachidonic acid (ARA), and phosphatidyl ethanolamines (PE), phosphatidyl cholines (PC) and downregulated the levels of l-valine and 5-hydroxyindole-3-acetic acid (5-HIAA) in plasma. The results indicated that the mechanisms of KDZI on MCAO/R were related to the mechanisms of amino acid and lipid metabolism. [ABSTRACT FROM AUTHOR]

Aim. In routine histopathology, decalcification is an essential step for mineralized tissues. The purpose of this study is to evaluate the effects of different decalcification solutions on the morphological and antigenicity preservation in Sprague Dawley (SD) rat femurs. Materials and Methods. Four different decalcification solutions were employed to remove the mineral substances from rat femurs, including 10% neutral buffered EDTA, 3% nitric acid, 5% nitric acid, and 8% hydrochloric acid/formic acid. Shaking and low temperature were used to process the samples. The stainings of hematoxylin-eosin (HE) and immunohistochemical (IHC) were employed to evaluate the bone morphology and antigenicity. Key Findings. Different decalcification solutions may affect the quality of morphology and the staining of paraffin-embedded sections in pathological examinations. Among four decalcifying solutions, 3% nitric acid is the best decalcifying agent for HE staining. 10% neutral buffered EDTA and 5% nitric acid are the preferred decalcifying agents for IHC staining. Significance. The current study investigated the effects of different decalcifying agents on the preservation of the bone structure and antigenicity, which will help to develop suitable protocols for the analyses of the bony tissue. [ABSTRACT FROM AUTHOR]

Kelisha capsules (KLS) are often used to treat acute diarrhoea, bacillary dysentery, heat stroke, and other diseases. One of its components, Asarum , contains aristolochic acid I which is both nephrotoxic and carcinogenic. However, the aristolochic acid (AA) content in KLS and its toxicity remain unclear. The aims of this study were to quantitatively determine the contents of five aristolochic acid analogues (AAAs) in Asarum and KLS, and systematically evaluate the in vivo toxicity of KLS in rats. Ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was used to determine the content of the five AAAs in Asarum and KLS. Sprague–Dawley rats were administered KLS at 0, 0.75, 1.5, and 3.0 g/kg respectively, and then sacrificed after 4 weeks of administration or after an additional 2 weeks of recovery. The endpoints assessed included body weight measurements, serum biochemistry and haematology indices, and clinical and histopathological observations. The AAAs content in Asarum sieboldii Miq. (HB-ESBJ) were much lower than those of the other Asarums. The contents of AA I, AA IVa, and aristolactam I in KLS were in the ranges of 0.03–0.06 μg/g, 1.89–2.16 μg/g, and 0.55–1.60 μg/g, respectively, whereas AA II and AA IIIa were not detected. None of the rats showed symptoms of toxic reactions and KLS was well tolerated throughout the study. Compared to the control group, the activated partial thromboplastin time values of rats in the 1.5 and 3.0 g/kg groups significantly reduced after administration (P < 0.05). In addition, the serum triglycerides of male rats in the 0.75 and 1.5 g/kg groups after administration, and the 0.75, 1.5, 3.0 g/kg groups after recovery were significantly decreased (P < 0.01 or P < 0.001). No significant drug-related toxicological changes were observed in other serum biochemical indices, haematology, or histopathology. The AA I content in KLS met the limit requirements (<0.001%) of the Chinese Pharmacopoeia. Therefore, it is safe to use KLS in the short-term. However, for safety considerations, attention should be paid to the effects of long-term KLS administration on coagulation function and triglyceride metabolism. [Display omitted] • Trace amounts of AA I, AA IVa, and AL I were detected in KLS. • No renal, hepatic, or other tissue damage was observed in long-term administration. • Attention should be paid to the coagulation function and triglyceride metabolism. [ABSTRACT FROM AUTHOR]

Aristolochic acid (AA)-IIIa is an AA analog present in Aristolochiaceae plants. To evaluate the chronic toxicity of AA-IIIa, mice were intragastrically administered with media control, 1 mg/kg AA-IIIa, and 10 mg/kg AA-IIIa, and designated as the control (CTL), AA-IIIa low dose (AA-IIIa-L), and AA-IIIa high dose (AA-IIIa-H) groups, respectively. AA-IIIa was administered three times a week, every other day, for 24 weeks (24-week time point). Thereafter, some mice were sacrificed immediately, while others were sacrificed 29 or 50 weeks after AA-IIIa withdrawal (53- or 74-week time point). Serum and organs were collected for biochemical and pathological analyses, respectively. Whole-genome sequencing was performed on the kidney, liver, and stomach tissues of AA-IIIa-treated mice for single-nucleotide polymorphism (SNP) detection. AA-IIIa-H mice died at 66 weeks, and the remaining mice showed moribund conditions at the 69 weeks. AA-IIIa induced minor kidney tubule injury, fibroblast hyperplasia, and forestomach carcinoma in mice. Bladder, intestine, liver, heart, spleen, lung, and testis tissues were not pathologically altered by AA-IIIa. In addition, AA-IIIa increased the C:G > A:T mutation in the kidney; however, no SNP mutation changes were observed in the liver and forestomach tissues of AA-IIIa-H mice at the 24-week time point compared with control mice. Therefore, we suspect that AA-IIIa is potentially mutagenic for mice after overdose and long-term administration. On the other hand, the forestomach is a unique organ in mice, but it does not exist in humans; thus, we hypothesize that the stomach toxicity induced by AA-IIIa is not a suitable reference for toxicological evaluation in humans. We recommend that Aristolochiaceae plants containing AA-IIIa should be properly supervised, and overdosing and long-term administration of drugs containing AA-IIIa should be avoided. [ABSTRACT FROM AUTHOR]

The two-dimensional (2D) material PbSnS 2 , a type of transition metal dichalcogenides (TMD), is a highly anisotropic layered compound with potential applications in ultrafast optics. We prepared PbSnS 2 nanosheets by liquid phase exfoliation, attached them to microfibers to fabricate saturable absorbers (SAs) by optical deposition method, and successfully applied them to a passive erbium-doped fiber laser (EDFL). In addition, the saturable absorption properties of PbSnS 2 -based SA were confirmed using a balanced two-detector measurement system. The results demonstrate that the PbSnS 2 -based SA can realize different stable mode-locked states in the same EDFL cavity, including fundamental frequency conventional soliton and 15th harmonic mode-locked states. Among them, the laser produced fundamental frequency mode-locked state with a signal-to-noise ratio of 59.51 dB (6.58 MHz repetition frequency). The HML pulse with a maximum repetition frequency of 98.71 MHz (corresponding to the 15th harmonic) was obtained. The results demonstrate that PbSnS 2 is a candidate material for generating ultrafast pulses and has excellent potential for application in ultrafast lasers. • PbSnS 2 exhibits unique anisotropic properties, ideal for ultrafast optical applications. • PbSnS 2 -based SAs excel in saturable absorption, promoting soliton formation and stable pulses. • The laser with PbSnS 2 -based SAs achieves multiple stable mode-locked states, increasing application flexibility. • Fundamental and 15th harmonic pulses deliver femtosecond durations, enabling ultrafast pulse creation. [ABSTRACT FROM AUTHOR]

[Display omitted] • Curdione, neocurdione, and curcumol are reversible and competitive inhibitors of CYP2B6. • Curdione, neocurdione, and curcumol contribute to the inhibition of zedoary turmeric oil on CYP2B6. • Curdione and neocurdione can be hydroxylated into hydroxycurdione and hydroxyneocurdione by CPY2B6, respectively. [ABSTRACT FROM AUTHOR]

• PbSnS 2 is potentially used in ultrafast optics, especially in high-frequency harmonic pulsed fiber lasers. • PbSnS 2 -SA shows a modulation depth of 11.54 %, highlighting its potential for generating ultrashort pulses. • The erbium-doped (Er-OFS) fiber laser with PbSnS 2 -SA achieved a fundamental frequency mode-locking of 738.3 fs. • Both fundamental and harmonic mode-locked operations were obtained in the erbium-doped (Er-110) fiber laser. This study explores the potential of lead-tin sulfide (PbSnS 2), a novel two-dimensional material, for optical applications. PbSnS 2 has a narrow bandgap and excellent light absorption, yet research on the optical characterization of PbSnS 2 is still in its infancy, especially in applying its saturable adsorption properties to ultrafast photonics. This work focuses on the pulse output characterization of a fiber laser based on the saturable absorber (SA) of PbSnS 2. High-quality PbSnS 2 nanosheets were prepared using liquid-phase exfoliation. SAs with high damage thresholds were obtained by depositing PbSnS 2 nanosheets on microfiber using a laser-induced process and applying them to nonlinear processes in ultrafast photonics. We report mode-locked and harmonic mode-locked generation in both (Er-110)- and (Er-OFS)-doped fiber lasers by using the same PbSnS 2 SA. To our knowledge, this is the first report of a PbSnS 2 -based fiber laser at 1.5-μm band. Our research demonstrates the significant potential and capability of PbSnS 2 -based saturable absorbers in achieving harmonic pulse operation with a high repetition frequency. This finding further advances the exploratory investigation of optoelectronic devices based on transition metal dichalcogenides. [ABSTRACT FROM AUTHOR]

Cholestasis is the main manifestation of cholestatic liver disease, which has a risk of progression to end-stage liver disease. Gardeniae Fructus is the dried fruit of Gardeniae jasminoides Ellis, a plant of the Rubiaceae family. Gardeniae Fructus has shown therapeutic potential in cholestasis-related liver diseases and it is generally believed that Gardeniae Fructus ameliorates cholestasis, which could be related to its influence on bile acids (BAs) metabolism. However, the specific targets of Gardeniae Fructus and its impact on enterohepatic circulation of BAs have not yet been fully elucidated. To systematically elucidate the mechanism by which Gardenia extract (GE, total iridoids in Gardeniae Fructus, which contains the predominant and characteristic phytoconstituents of Gardeniae Fructus) ameliorates alpha-naphthylisothiocyanate (ANIT)-induced cholestatic liver injury. Sprague-Dawley rats were orally administered water, obeticholic acid (OCA, 2 mg/kg), or GE (21 and 42 mg/kg) once daily for five days. On the third day, the model was established by administration of a single dose of ANIT (40 mg/kg) by oral gavage. Biochemical and pathological analyses, BA metabolomics, transcriptomics, and qRT-PCR were performed. The profile of BAs in serum and liver confirmed that GE attenuated ANIT-induced acute cholestasis by affecting BA metabolism in a dose-dependent manner. Liver transcriptomic analysis indicated that GE mainly influenced the primary bile acid (PBA) biosynthesis and bile secretion pathways. GE mainly affected PBA biosynthesis in liver by upregulating Cyp8b1 gene expression, thereby significantly reducing the level of total bile acids (TBA). GE mainly promoted PBA excretion from liver into duodenum by upregulating Fxr and Oatp1 gene expression, thereby increasing the excretion of PBA in feces, and inhibiting PBA in liver entering the blood by alternative routes to reduce TBA levels in serum and urine and improve the enterohepatic circulation of BAs. GE attenuated ANIT-induced hepatotoxicity and cholestasis in rats by upregulating Cyp8b1 expression to inhibit BA synthesis in the liver, while also promoting BA excretion via the intestinal-fecal route, and improving enterohepatic circulation of BAs. [Display omitted] • Gardenia extract (GE) attenuated ANIT-induced hepatotoxicity and cholestasis in rats. • GE inhibits the synthesis of BAs in the liver by upregulating the expression of Cyp8b1. • GE promoted BA excretion, and improved enterohepatic circulation of BAs. [ABSTRACT FROM AUTHOR]

Cinnamaldehyde, one of the active components derived from Cinnamon, has been used as a natural flavorant and fragrance agent in kitchen and industry. Emerging studies have been performed over the past decades to evaluate its beneficial role in management of diabetes and its complications. This review highlights recent advances of cinnamaldehyde in its glucolipid lowering effects, its pharmacokinetics, and its safety by consulting the Pubmed, China Knowledge Resource Integrated, China Science and Technology Journal, National Science and Technology Library, Wanfang Data, and the Web of Science Databases. For the inquiries, keywords such as Cinnamon, cinnamaldehyde, property, synthesis, diabetes, obesity, pharmacokinetics, and safety were used in various combinations. Accumulating evidence supports the notion that cinnamaldehyde exhibits glucolipid lowering effects in diabetic animals by increasing glucose uptake and improving insulin sensitivity in adipose and skeletal muscle tissues, improving glycogen synthesis in liver, restoring pancreatic islets dysfunction, slowing gastric emptying rates, and improving diabetic renal and brain disorders. Cinnamaldehyde exerts these effects through its action on multiple signaling pathways, including PPARs, AMPK, PI3K/IRS-1, RBP4-GLUT4, and ERK/JNK/p38MAPK, TRPA1-ghrelin and Nrf2 pathways. In addition, cinnamaldehyde seems to regulate the activities of PTP1B and α-amylase. Furthermore, cinnamaldehyde has the potential of metalizing into cinnamyl alcohol and methyl cinnamate and cinnamic acid in the body. Finally, there is a potential toxicity concern about this compound. In summary, cinnamaldehyde supplementation is shown to improve glucose and lipid homeostasis in diabetic animals, which may provide a new option for diabetic intervention. To this end, further scientific evidences are required from clinical trials on its glucose regulating effects and safety. [ABSTRACT FROM AUTHOR]

Curcumin, a polyphenol derived from the turmeric, has received attention as a potential treatment for renal fibrosis primarily because it is a relatively safe and inexpensive compound that contributes to kidney health. Here, we review the literatures on the applications of curcumin in resolving renal fibrosis in animal models and summarize the mechanisms of curcumin and its analogs (C66 and (1E,4E)-1,5-bis(2-bromophenyl) penta-1,4-dien-3-one(B06)) in preventing inflammatory molecules release and reducing the deposition of extracellular matrix at the priming and activation stage of renal fibrosis in animal models by consulting PubMed and Cnki databases over the past 15 years. Curcumin exerts antifibrotic effect through reducing inflammation related factors (MCP-1, NF-κB, TNF-α, IL-1β, COX-2, and cav-1) and inducing the expression of anti-inflammation factors (HO-1, M6PRBP1, and NEDD4) as well as targeting TGF-β/Smads, MAPK/ERK, and PPAR-γ pathways in animal models. As a food derived compound, curcumin is becoming a promising drug candidate for improving renal health. [ABSTRACT FROM AUTHOR]

Purpose: Increasing evidence supported that semaphorin 3A (Sema3A), insulin-like growth factor (IGF)-1 and β-catenin were involved in the development of osteoporosis and diabetes. This study is aimed to evaluate whether Sema3A/IGF-1/β-catenin is directly involved in the alterations of bone microarchitecture and bone strength of diabetic rats. Methods: Diabetic rats were induced by streptozotocin and high fat diet exposure. Bone microarchitecture and strength in the femurs were evaluated by micro-CT scanning, three-point bending examination and the stainings of HE, alizarin red S and safranin O/fast green, respectively. The alterations of lumbar spines microarchitecture were also determined by micro-CT scanning. Western blot and immunohistochemical analyses were used to examine the expression of Sema3A, β-catenin, IGF-1, peroxisome proliferator-activated receptor γ (PPARγ) and cathepsin K in rat tibias. Results: Diabetic rats exhibited decreased trabecular numbers and bone formation, but an increased trabecular separation in the femurs and lumbar spines. Moreover, the increased bone fragility and decreased bone stiffness were evident in the femurs of diabetic rats. Diabetic rats also exhibited a pronounced bone phenotype which manifested by decreased expression of Sema3A, IGF-1 and β-catenin, as well as increased expression of cathepsin K and PPARγ. Conclusions: This study suggests that diabetes could perturb bone loss through the Sema3A/IGF-1/β-catenin pathway. Sema3A deficiency in bone may contribute to upregulation of PPARγ and cathepsin K expression, which further disrupts bone remodeling in diabetic rats. [ABSTRACT FROM AUTHOR]

Asarum heterotropoides f. mandshuricum (Maxim.) Kitag. (AH) is widely used to treat influenza, COVID-19, allergic rhinitis, headache, toothache, rheumatoid arthritis, and peptic ulcer. However, its clinical use is controversial due to the concern of aristolochic acid nephropathy (AAN) caused by its component aristolochic acid analogs (AAs). The chronic toxicity of AH decoction and its main components AA IVa (AA-IVa) and aristolactam I (AL-I) was evaluated in mice. AAs contents in AH were quantitated by liquid chromatography-mass spectrometry. A parallel design was employed to examine the potential chronic toxicity of AH decoction at doses equivalent to 0.5, 1.6, and 5.0 g/kg AH (approximately 10–100 times the clinical doses for humans) and its major AA components at doses equivalent to that in 5.0 g/kg AH to mice after consecutive daily oral administration for 12 and 24 weeks, and at 32 weeks after withdrawal for 8 weeks. AH crude herb contained 2.18 μg/g of AA-I, 48.49 μg/g of AA-IVa, and 14.0 μg/g of AL-I. AH decoction contained 5.45 μg/g of AA-IVa and 2.71 μg/g of AL-I. None of AA-II and AA-IIIa were detected in AH. After long-term administration of AH decoction and its major components AA-IVa and AL-I, mice showed no signs of illness or body weight changes. In addition, biochemical and pathohistological examinations showed that long-term administration of AH decoction and its major components AA-IVa and AL-I did not alter 1) serum levels of glutamic-pyruvic transaminase, glutamic oxalacetic transaminase, alkaline phosphatase, creatinine, and urea nitrogen, 2) renal tissue mRNA expression of kidney injury molecule 1 and neutrophil gelatinase-associated lipocalin, and 3) pathological morphology in the mouse liver, kidney, stomach, and bladder. AH has no obvious toxicity to mice and is relatively safe when it is used in the form of decoction. AA-IVa and AL-I, the two major AAs in AH, are not toxic to mice at the dose equivalent to that in the high dose of AH decoction. Considering the limited toxicological data on AH, we recommend that AH decoction medication should not overdose and the duration should not be too long. [Display omitted] • Quantitation of AAs in AH. • Evaluating the toxicity of AH decoction and its AAs. • Providing AH decoction medication suggestion. [ABSTRACT FROM AUTHOR]

Aim. The incidence of diabetic osteoporosis (DOP) is increasing due to lack of effective management over the past few decades. This review aims to summarize traditional Chinese medicine (TCM) suitability in the pathogenesis and clinical and preclinical management of DOP. Methods. Literature sources used were from Medline (Pubmed), CNKI (China Knowledge Resource Integrated Database), and CSTJ (China Science and Technology Journal Database) online databases. For the consultation, keywords such as diabetic osteoporosis (DOP), TCM, clinical study, animal experiment, toxicity, and research progress were used in various combinations. Around 100 research papers and reviews were visited. Results. Liver-spleen-kidney insufficiency may result in development of DOP. 18 clinical trials are identified to use TCM compound prescriptions for management of patients with DOP. TCM herbs and their active ingredients are effective in preventing the development of DOP in streptozotocin (STZ) and alloxan as well as STZ combined with ovariectomy insulted rats. Among them, most frequently used TCM herbs in clinical trials are Radix Astragali, Radix et Rhizoma Salviae Miltiorrhizae, Radix Rehmanniae Preparata, and Herba Epimedii. Some of TCM herbs also exhibit toxicities in clinical and preclinical research. Conclusions. TCM herbs may act as the novel sources of anti-DOP drugs by improving bone and glucolipid metabolisms. However, the pathogenesis of DOP and the material base of TCM herbs still merit further study. [ABSTRACT FROM AUTHOR]

Lycopene (LYC), one of the major carotenoids in tomatoes, has been preclinically and clinically used to obesity and type 2 diabetes management. However, whether its ability of countering body weight gain is related to induction of brown-like adipocyte phenotype in white adipose tissues (WAT) remains largely unknown. Activation of peroxisome proliferator-activated receptor γ (PPARγ) serves the brown-like phenotype conversion and energy expenditure. Here, we show that LYC treatment promotes glucose consumption and improves insulin sensitivity, as well as fosters white adipocytes browning through up-regulating mRNA and protein expression levels of PPARγ, uncoupling protein 1, PPARγ coactivator-1α and PR domain-containing 16 in the differentiated 3T3-L1 adipocytes and primary adipocytes, as well as in the WAT of HFD-exposed obese mice. In addition, LYC treatment attenuates body weight gain and improves serum lipid profiles as well as promotes brown adipose tissue activation in obese mice. Moreover, PPARγ is induced with LYC intervention in mitochondria respiration and browning in white adipocytes and tissues. Taken together, these results suggest that LYC counteracts obesity and improves glucose and lipid metabolism through induction of the browning via up-regulation of PPARγ, which offers a new perspective of this compound to combat obesity and obesity-related disorders. [ABSTRACT FROM AUTHOR]

With the improvement of living standards and a change in lifestyle, the incidence of type 2 diabetes mellitus (T2DM) is increasing. Its etiology is too complex to be completely understand yet. Metabonomics techniques are used to study the changes of metabolites and metabolic pathways before and after the onset of diabetes and make it more possible to further understand the pathogenesis of T2DM and improve its prediction, early diagnosis, and treatment. In this review, we summarized the metabonomics study of T2DM in recent years and provided a theoretical basis for the study of pathogenesis and the effective prevention and treatment of T2DM. [ABSTRACT FROM AUTHOR]