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Danggui Buxue Decoction (DBD) is an effective complementary medicine in alleviating myelosuppression after chemotherapy (MAC). However, its mechanism of action is elusive. To illustrate that regulating β-hydroxybutyric acid (β-OHB) metabolism and suppressing oxidative stress could be a potential mechanism of action for DBD in alleviating MAC. After HPLC quantification and dose testing (3, 6 and 10 g/kg, gavage) of DBD, Sprague-Dawley rats were divided into control, cyclophosphamide (CTX) (30 mg/kg CTX for 5 days, intraperitoneal administration) and CTX + DBD groups (6 g/kg DBD for 14 days, gavage). Blood cell counts, thigh bone histological examination, β-OHB levels, oxidative stress indices and HDAC1 activity were tested. The biological function of β-OHB was verified in vitro (hBMSC cells were incubated in culture mediums that contained 40 μM CTX and β-OHB in 0, 1, 2.5, 5, 10 mM) and in vivo (MAC rat model, 3 g/kg β-OHB for 14 days, gavage). Rats in the CTX + DBD group showed upregulated blood cell counts (118–243%), β-OHB levels (495 nmol/mL in blood, 122 nmol/mg in marrow supernatant) and downregulated HDAC1 activity (59%), and oxidative stress indices (60–85%). In vitro, 5 mM β-OHB improved hBMSC cell migration (123%) and proliferation (131%). In vivo, rats treated with 3 g/kg β-OHB showed upregulated blood cell counts (121–182%) and downregulated HDAC1 activity (64%) and oxidative stress indices (65–83%). DBD, a traditional Chinese medicine, alleviates MAC by intervening in β-OHB metabolism and oxidative stress. [ABSTRACT FROM AUTHOR]

Targeted imaging is playing an increasingly important role in the early detection and precise diagnosis of cancer. This need has motivated research into sensory nanomaterials that can be constructed into imaging agents to serve as biosensors. Graphene quantum dots (GQDs) as a valuable nanoprobe show great potential for use in two-photon biological imaging. However, most as-prepared GQDs exhibit a low two-photon absorption cross-section, narrow spectral coverage, and "one-to-one" signal conversion mode, which greatly hamper their wide application in sensitive early-stage cancer detection. Herein, a versatile strategy has been employed to fabricate an aptamer Sgc8c-functionalized hybrid as a proof-of-concept of the signal amplification strategy for targeted cancer imaging. In this study, GQDs with two-photon imaging performance, and silica nanoparticles (SiO2 NPs) as nanocarriers to provide amplified recognition events by high loading of GQD signal tags, were adopted to construct a two-photon hybrid-based signal amplification strategy. Thus, the obtained hybrid (denoted SiO2@GQDs) enabled extremely strong fluorescence with a quantum yield up to 0.49, excellent photostability and biocompatibility, and enhanced bright two-photon fluorescence up to 2.7 times that of bare GQDs (excitation at 760 nm; emission at 512 nm). Moreover, further modification with aptamer Sgc8c showed little disruption to the structure of the SiO2@GQDs-hybrid and the corresponding two-photon emission. Hence, SiO2@GQDs–Sgc8c showed specific responses to target cells. Moreover, it could be used as a signal-amplifying two-photon nanoprobe for targeted cancer imaging with high specificity and great efficiency, which exhibits a distinct green fluorescence compared to that of GQDs–Sgc8c or SiO2@GQDs. This signal amplification strategy holds great potential for the accurate early diagnosis of tumors and offers new tools for the detection a wide variety of analytes in clinical application. [ABSTRACT FROM AUTHOR]

Abstract The ability of LC-MS/MS for high coverage metabolite analysis lags behind the requirements of global metabolomics. The introduction of chemical derivatizations could significantly extend the ability of LC-MS/MS with enhanced MS response and improved LC separation, which has been serving as a promising quantitative tool for metabolomic analysis. However, as one specific derivatization reagent usually targets to a certain moiety, only a single chemical-group-based submetabolome could be analyzed in one injection. Therefore, the coverage of detected metabolites by derivatization-based LC-MS/MS is largely limited. To overcome this technical obstacle of derivatization-based LC-MS and increase submetabolome coverage, we proposed an extendable all-in-one injection LC-MS/MS strategy. 5-dimethylamino-naphthalene-1-sulfonyl chloride (Dns-Cl)/5-diethylamino-naphthalene-1-sulfonyl chloride (Dens-Cl) and 5-dimethylamino-naphthalene-1-sulfonyl piperazine (Dns-PP)/5-diethylamino-naphthalene-1-sulfonyl piperazine (Dens-PP) were used as twins labeling reagents for amino/phenol and carboxyl submetabolomes, respectively. "Series Mode" and "Parallel Mode" were proposed and investigated using eight representative standards with the consideration of interaction between different derivatization systems, time-consumption, and extendability. As a result, we found that "Series Mode" led to yield reduction, while "Parallel Mode" gave identical results with those of individual derivatization. Finally, a "Parallel Mode" was chosen to develop an extendable all-in-one injection twin derivatization LC-MS/MS strategy to quantify eighty metabolites assigned to five classes of microbial metabolites, including polyamines, amino acids, indole derivatives, bile acids, and free fatty acids. This well-validated method quantified 67 metabolites absolutely and discovered additional 40 differential metabolites compared with the untargeted method in rat serum from irinotecan (CPT-11)-induced gastrointestinal toxicity model. Graphical abstract Image 1 Highlights • This strategy was developed for chemical derivatization-based LC-MS/MS. • "Parallel Mode" was better in derivatization efficiency, time-consumption and extensibility. • Multiple submetabolomes with different labeling were quantified in one injection. • 40 additional differential metabolites were found compared with untargeted method. • All-in-one injection strategy should be useful for global metabolomics. [ABSTRACT FROM AUTHOR]

To better understand different traditional uses of the stems (known as Mahuang) and roots (known as Mahuanggen) of Ephedra sinica, their chemical difference should be investigated. In this study, an ultra-fast liquid chromatography coupled with ion trap time-of-flight mass spectrometry untargeted metabolomics approach was established to reveal global chemical difference between Mahuang and Mahuanggen. Clear separation was observed in scores plots of principal component analysis and orthogonal partial least squares-discriminant analysis. Twenty two chemical markers responsible for such separation were screened out and unambiguously/tentatively characterized. Then chemical markers of pharmacologically important ephedrine and pseudoephedrine were absolutely quantified using liquid chromatography coupled with tandem mass spectrometry under multiple reaction monitoring mode. The results showed that Mahuang was rich in ephedrine-type alkaloids, while Mahuanggen was rich in macrocyclic spermine alkaloids. Additionally, different types of flavan-3-ols and flavones exist in Mahuang and Mahuanggen extracts. This research facilitates a better understanding of different traditional uses of Mahuang and Mahuanggen and provides references for chemical analysis of other medicinal plants. [ABSTRACT FROM AUTHOR]

Aim: To assess the association between acute phase treatment by valproate as an adjunctive drug and risk of new onset hypothyroidism in a large cohort of patients affected by schizophrenia.Methods: We conducted a retrospective cohort study in a psychiatric hospital in China between January 2016 and December 2018. We obtained approval from the Ethics Committee of the study hospital prior to the commencement of the study. Patients who were diagnosed with schizophrenia and admitted to the study hospital during the study period with thyroid function tests at admission and during hospitalization were included. Patients with abnormal thyroid function at admission were excluded. Hypothyroidism, defined as TSH>4.2 mU/L or on L-thyroxine treatment, was the primary outcome. The primary exposure was adjunctive valproate plus atypical antipsychotics (AAPD), the secondary exposure was lithium plus AAPD and the comparison group was AAPD only. Adjusted relative risk (RR) and 95% confidence interval (CI) were estimated by log-binomial model to assess the independent association between valproate treatment and risk of hypothyroidism.Results: A total of 1622 eligible patients were included the final analysis. Rate of new onset hypothyroidism was 10.7% and 20.9% in AAPD only and valproate plus AAPD groups, respectively. Adjusted RR (95% CI) for valproate plus AAPD was 1.85 (1.44-2.38), with AAPD only group as reference. Similarly, adjusted RR (95% CI) for lithium plus AAPD was 1.93 (1.32-2.69).Conclusion: Similar with lithium, valproate as adjunctive drug is associated with increased risk of new onset hypothyroidism during acute phase treatment for schizophrenia. [ABSTRACT FROM AUTHOR]

Branched-chain amino acids (BCAAs) and branched-chain α-keto acids (BCKAs) play significant biological roles as they are involved in protein and neurotransmitter synthesis as well as energy metabolism pathways. To routinely and accurately study the dynamics of BCAAs and BCKAs in human diseases, e.g. cerebral infarction, a novel liquid chromatography-tandem mass spectrometry (LC-MS/MS) method has been developed and validated. The plasma samples were deproteinized with acetonitrile, and then separated on a reversed phase C18 column with a mobile phase of 0.1 % formic acid (solvent A)-methanol (solvent B) using gradient elution. The detection of BCAAs and BCKAs was conducted in multiple reaction monitoring with positive/negative electrospray ionization switching mode. Biologically relevant isomers such as leucine and isoleucine were individually quantified by combining chromatographic separation and fragmentation. Good linearity ( R > 0.99) was obtained for all six analytes with the limits of detection from 0.1 to 0.2 µg/mL. The intra-day and inter-day accuracy ranged from 93.7 to 108.4 % and the relative standard deviation (RSD) did not exceed 15.0 %. The recovery was more than 80 % with RSD less than 14.0 %. The main improvements compared to related, state-of-the-art methods included enhanced sensitivity, enhanced separation of isomers, and reduced complexity of sample processing. Finally, the validated method was applied to analyze the plasma samples of healthy volunteers and patients suffering cerebral infarction, and significant differences in the concentration levels of BCAAs and BCKAs were observed. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Seven species from the genus Dictamnus are distributed throughout Europe and North Asia and only two species grow in China. One is Dictamnus dasycarpus Turcz., which could be found in many areas of China and has been recorded in Chinese Pharmacopoeia . The other is Dictamnus angustifolius G. Don ex Sweet, which is only present in Xinjiang province and has been used as an alternative for Dictamnus dasycarpus in the local for the treatment of rheumatism, bleeding, itching, jaundice, chronic hepatitis and skin diseases. The present paper reviewed the traditional uses, phytochemistry, pharmacology and toxicology of the genus Dictamnus . Materials and methods Information on the Dictamnus species was collected from classic books about Chinese herbal medicine and globally accepted scientific databases including PubMed, Elsevier, ASC, Scopus, Google Scholar, Web of Science, CNKI and others. Results About 170 chemical compounds, which include quinoline alkaloids, limonoids, sesquiterpenes, coumarins, flavonoids and steroids, have been isolated from the genus Dictamnus . The characteristic and active constituents of Dictamnus species are considered to be quinoline alkaloids and limonoids, which exhibited a broad spectrum of biological activities such as anti-cancer, anti-inflammation, anti-microbe, anti-platelet-aggregation, vascular-relaxation, anti-insect, anti-HIV, anti-allergy and neuroprotection. Moreover, quinoline alkaloids and limonoids could be used as quality control markers to distinguish different species from the genus Dictamnus . However, there were also some reports on the toxic hepatitis and phototoxic effect of Dictamnus species, and the related research needs to be further studied. Conclusion In this review, we summarized the chemical constituents, pharmacology, quality control and toxicology of the species from genus Dictamnus . Phytochemical investigations indicated that quinoline alkaloids and limonoids were the major bioactive components with potential cytotoxic, neuroprotective, anti-inflammatory, antimicrobial, anti-platelet-aggregation and vascular relaxing activities. These two kinds of compounds have attracted great interests in the past few years and may have great potential to be new drug lead compounds. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Seven species from the genus Dictamnus are distributed throughout Europe and North Asia and only two species grow in China. One is Dictamnus dasycarpus Turcz., which could be found in many areas of China and has been recorded in Chinese Pharmacopoeia . The other is Dictamnus angustifolius G. Don ex Sweet, which is only present in Xinjiang province and has been used as an alternative for Dictamnus dasycarpus in the local for the treatment of rheumatism, bleeding, itching, jaundice, chronic hepatitis and skin diseases. The present paper reviewed the traditional uses, phytochemistry, pharmacology and toxicology of the genus Dictamnus . Materials and methods Information on the Dictamnus species was collected from classic books about Chinese herbal medicine and globally accepted scientific databases including PubMed, Elsevier, ASC, Scopus, Google Scholar, Web of Science, CNKI and others. Results About 170 chemical compounds, which include quinoline alkaloids, limonoids, sesquiterpenes, coumarins, flavonoids and steroids, have been isolated from the genus Dictamnus . The characteristic and active constituents of Dictamnus species are considered to be quinoline alkaloids and limonoids, which exhibited a broad spectrum of biological activities such as anti-cancer, anti-inflammation, anti-microbe, anti-platelet-aggregation, vascular-relaxation, anti-insect, anti-HIV, anti-allergy and neuroprotection. Moreover, quinoline alkaloids and limonoids could be used as quality control markers to distinguish different species from the genus Dictamnus . However, there were also some reports on the toxic hepatitis and phototoxic effect of Dictamnus species, and the related research needs to be further studied. Conclusion In this review, we summarized the chemical constituents, pharmacology, quality control and toxicology of the species from genus Dictamnus . Phytochemical investigations indicated that quinoline alkaloids and limonoids were the major bioactive components with potential cytotoxic, neuroprotective, anti-inflammatory, antimicrobial, anti-platelet-aggregation and vascular relaxing activities. These two kinds of compounds have attracted great interests in the past few years and may have great potential to be new drug lead compounds. [ABSTRACT FROM AUTHOR]