Hydroxychloroquine: Key therapeutic advances and emerging nanotechnological landscape for cancer mitigation.

Hydroxychloroquine (HCQ) is a unique class of medications that has been widely utilized for the treatment of cancer. HCQ plays a dichotomous role by inhibiting autophagy induced by the tumor microenvironment (TME). Preclinical studies support the use of HCQ for anti-cancer therapy, especially in combination with conventional anti-cancer treatments since they sensitize tumor cells to drugs, potentiating the therapeutic activity. However, clinical evidence has suggested poor outcomes for HCQ due to various obstacles, including non-specific distribution, low aqueous solubility and low bioavailability at target sites, transport across tissue barriers, and retinal toxicity. These issues are addressable via the integration of HCQ with nanotechnology to produce HCQ-conjugated nanomedicines. This review aims to discuss the pharmacodynamic, pharmacokinetic and antitumor properties of HCQ. Furthermore, the antitumor performance of the nanoformulated HCQ is also reviewed thoroughly, aiming to serve as a guide for the HCQ-based enhanced treatment of cancers. The nanoencapsulation or nanoconjugation of HCQ with nanoassemblies appears to be a promising method for reducing the toxicity and improving the antitumor efficacy of HCQ.

A Q-marker screening strategy based on ADME studies and systems biology for Chinese herbal medicine, taking Qianghuo Shengshi decoction in treating rheumatoid arthritis as an example.

Chinese herbal medicine (CHM) exhibits a broad spectrum of clinical applications and demonstrates favorable therapeutic efficacy. Nonetheless, elucidating the underlying mechanism of action (MOA) of CHM in disease treatment remains a formidable task due to its inherent characteristics of multi-level, multi-linked, and multi-dimensional non-linear synergistic actions. In recent years, the concept of a Quality marker (Q-marker) proposed by Liu et al. has significantly contributed to the monitoring and evaluation of CHM products, thereby fostering the advancement of CHM research. Within this study, a Q-marker screening strategy for CHM formulas has been introduced, particularly emphasising efficacy and biological activities, integrating absorption, distribution, metabolism, and excretion (ADME) studies, systems biology, and experimental verification. As an illustrative case, the Q-marker screening of Qianghuo Shengshi decoction (QHSSD) for treating rheumatoid arthritis (RA) has been conducted. Consequently, from a pool of 159 compounds within QHSSD, five Q-markers exhibiting significant in vitro anti-inflammatory effects have been identified. These Q-markers encompass notopterol, isoliquiritin, imperatorin, cimifugin, and glycyrrhizic acid. Furthermore, by employing an integrated analysis of network pharmacology and metabolomics, several instructive insights into pharmacological mechanisms have been gleaned. This includes the identification of key targets and pathways through which QHSSD exerts its crucial roles in the treatment of RA. Notably, the inhibitory effect of QHSSD on AKT1 and MAPK3 activation has been validated through western blot analysis, underscoring its potential to mitigate RA-related inflammatory responses. In summary, this research demonstrates the proposed strategy's feasibility and provides a practical reference model for the systematic investigation of CHM formulas.

Evaluation of reduced graphene oxide-based nanomaterial as dispersive solid phase extraction sorbent for isolation and purification of aflatoxins from poultry feed, combined with UHPLC-MS/MS analysis.

Poultry feed comprises cereals and their by-products and is vulnerable to aflatoxins contamination. This study utilised reduced graphene oxide-titanium dioxide (rGO-TiO2) nanomaterial as a dispersive solid phase extraction (d-SPE) adsorbent to extract, enrich and purify aflatoxins (aflatoxin B1, aflatoxin B2, aflatoxin G1 and aflatoxin G2). The synthesis of rGO-TiO2 nanomaterials through hydrothermal process and characterisation by transmission electron microscopy, scanning electron microscopy, Brunauer-Emmett-Teller (BET) and X-ray diffraction reveals that the nanomaterials have a single-layer structure embedded with TiO2 nanoparticles. The matrix-spiked technique was employed for the extraction process, optimisation of d-SPE, and analytical method validation. The most appropriate extraction solvent was acetonitrile/water/formic acid (79/20/1, v/v/v), with 30 min of extraction time assisted by ultra-sonication. The optimised d-SPE parameters were: 50 mg of rGO-TiO2 as sorbent amount, 2% methanol as the sample loading solvent, 30 min as adsorption time, and absolute ethanol as the washing reagent. The d-SPE method exhibited good desorption efficiency with 3 mL of acetonitrile/formic acid (99/1, v/v) and 20 min desorption time. After validation, the UHPLC-MS/MS analytical method has an acceptable range of specificity, linearity (R2 ≥ 0.999), sensitivity (LOQ 0.04-0.1 µg kg-1), recoveries (74-105% at three matrix-spiked levels) and precision (RSD 1.5-9.6%). Poultry feed samples (n = 12) were pretreated by this method to extract, enrich and analyse aflatoxins, which were detected in all poultry feed samples. The contamination levels were within the permissible limits.

Network pharmacology and metabolomics elucidate the underlying mechanisms of Venenum Bufonis in the treatment of colorectal cancer.

ETHNOPHARMACOLOGICAL RELEVANCE: The present study aims to evaluate the efficacy of Venenum Bufonis (VBF), a traditional Chinese medicine derived from the dried secretions of the Chinese toad, in treating colorectal cancer (CRC). The comprehensive roles of VBF in CRC through systems biology and metabolomics approaches have been rarely investigated. AIMS OF THE STUDY: The study sought to uncover the potential underlying mechanisms of VBF's anti-cancer effects by investigating the impact of VBF on cellular metabolic balance. MATERIALS AND METHODS: An integrative approach combining biological network analysis, molecular docking and multi-dose metabolomics was used to predict the effects and mechanisms of VBF in CRC treatment. The prediction was verified by cell viability assay, EdU assay and flow cytometry. RESULTS: The results of the study indicate that VBF presents anti-CRC effects and impacts cellular metabolic balance through its impact on cell cycle-regulating proteins, such as MTOR, CDK1, and TOP2A. The results of the multi-dose metabolomics analysis suggest a dose-dependent reduction of metabolites related to DNA synthesis after VBF treatment, while the EdU and flow cytometry results indicate that VBF inhibits cell proliferation and arrests the cell cycle at the S and G2/M phases. CONCLUSIONS: These findings suggest that VBF disrupts purine and pyrimidine pathways in CRC cancer cells, leading to cell cycle arrest. This proposed workflow integrating molecular docking, multi-dose metabolomics, and biological validation, which contented EdU assay, cell cycle assay, provides a valuable framework for future similar studies.

PD-1: A New Candidate Target for Analgesic Peptide Design.

Chronic pain is a common health problem in humans. The unique properties and valuable clinical applications of analgesic peptides make them attractive pharmacotherapy options for pain control. Numerous targets for pain modulation processes are currently known, including opioid receptors, transient receptor potential (TRP) channels, voltage-gated ion channels, neuronal nicotinic receptors, and neurotensin receptors. However, these targets are not able to address the development needs of peptide-based drugs. Recent studies revealed that programmed cell death 1 (PD-1) is widely expressed in the dorsal root ganglia (DRG), spinal cord, and cerebral cortex. PD-1 signaling in neurons is involved in the regulation of neuronal excitability, synaptic transmission, and synaptic plasticity. PD-1 is able to silence nociceptive neurons upon activation. Consistently, Pd1 deficiency or blockade increases the pain sensitivity in naïve mice. PD-1 agonists, including PD-L1 and H-20, evoke Src homology 2 domain-containing tyrosine phosphatase-1 (SHP-1) phosphorylation, modulate neuronal excitability, and attenuate acute and chronic pain with minimal opioid-related adverse effects, suggesting a superior therapeutic index and a sound strategy for the development novel nonopioid analgesics. In addition, PD-1 signaling in non-neuronal cells could alleviate chronic pain by regulating neuroinflammation. Here, we review the potential and challenges of PD-1 as a candidate target for the development of analgesic peptides. PERSPECTIVE: This review paper aims to review recent advances in research on PD-1 in the domain of pain interference, explore how to obtain more promising PD-1 receptor-targeting analgesic peptides based on PD-L1 and analgesic peptide H-20 for relieving pathological pain, and offer potential optimization strategies for follow-up work of H-20.

Exploration of the anti-inflammatory mechanism of Lanqin oral solution based on the network pharmacology analysis optimized by Q-markers selection.

Network pharmacology is widely used to predict the mechanism of traditional Chinese medicines (TCM), but the framework in traditional network pharmacology analysis ignores the relationship between the concentration of components and drug efficacy. Lanqin oral solution (LOS) is a TCM formulation that widely used in the clinical treatment of pharyngitis, but its pharmacodynamic mechanism is still unknown. The present study was designed to elaborate the anti-inflammatory mechanism of LOS based on the quality markers (Q-markers). The efficacy of LOS was correlated with the fingerprint common peaks by chemometrics to select key peaks, and the Q-markers were further confirmed by mass spectrometry. Network pharmacology analysis was performed based on the chosen Q-markers to elaborate the potential pharmacodynamic mechanisms. Four efficacy-related chromatographic peaks were screened by the novel competitive adaptive reweighted sampling (CARS) spectrum-effect relationship analysis and series of other chemometrics methods. Four peaks were further characterized as the Q-markers in the LOS by mass spectrometry, i.e., geniposide, berberine, palmatine and baicalin. The ingredient-target network demonstrated that the LOS showed more impact on the NF-κB signaling pathway to elicit anti-inflammatory ability. Overall, the present study has introduced CARS into the spectrum-effect relationship analysis for the first time, which complemented the commonly applied chemometric methods. The network established based on the screened Q-markers was highly interpretable and successfully achieved the prediction of the anti-inflammatory mechanism of LOS. The proposed workflow provides a systematic method for exploring the mechanism of TCM based on identifying efficacy indicators. More importantly, it offers a reference for clarifying the mechanisms for other TCM formulations.

Feasibility of an NIR spectral calibration transfer algorithm based on optimized feature variables to predict tobacco samples in different states.

The prediction accuracy of calibration models for near-infrared (NIR) spectroscopy typically relies on the morphology and homogeneity of the samples. To achieve non-homogeneous tobacco samples for non-destructive and rapid analysis, a method that can predict tobacco filament samples using reliable models based on the corresponding tobacco powder is proposed here. First, as it is necessary to establish a simple and robust calibrated model with excellent performance, based on full-wavelength PLSR (Full-PLSR), the key feature variables were screened by three methods, namely competitive adaptive reweighted sampling (CARS), variable combination population analysis-iteratively retaining informative variables (VCPA-IRIV), and variable combination population analysis-genetic algorithm (VCPA-GA). The partial least squares regression (PLSR) models for predicting the total sugar content in tobacco were established based on three optimal wavelength sets and named CARS-PLSR, VCPA-IRIV-PLSR and VCPA-GA-PLSR, respectively. Subsequently, they were combined with different calibration transfer algorithms, including calibration transfer based on canonical correlation analysis (CTCCA), slope/bias correction (S/B) and non-supervised parameter-free framework for calibration enhancement (NS-PFCE), to evaluate the best prediction model for the tobacco filament samples. Compared with the previous two transfer algorithms, NS-PFCE performed the best under various wavelength conditions. The prediction results indicated that the most successful approach for predicting the tobacco filament samples was achieved by VCPA-IRIV-PLSR when coupled with the NS-PFCE method, which obtained the highest determination coefficient (Rp2 = 0.9340) and the lowest root mean square error of the prediction set (RMSEP = 0.8425). VCPA-IRIV simplifies the calibration model and improves the efficiency of model transfer (31 variables). Furthermore, it pledges the prediction accuracy of the tobacco filament samples when combined with NS-PFCE. In summary, calibration transfer based on optimized feature variables can eliminate prediction errors caused by sample morphological differences and proves to be a more beneficial method for online application in the tobacco industry.

Huntington-associated protein 1 inhibition contributes to neuropathic pain by suppressing Cav1.2 activity and attenuating inflammation.

ABSTRACT: Although pain dysfunction is increasingly observed in Huntington disease, the underlying mechanisms still unknown. As a crucial Huntington-associated protein, Huntington-associated protein 1 (HAP1) is enriched in normal spinal dorsal horn and dorsal root ganglia (DRG) which are regarded as "primary sensory center," indicating its potential functions in pain process. Here, we discovered that HAP1 level was greatly increased in the dorsal horn and DRG under acute and chronic pain conditions. Lack of HAP1 obviously suppressed mechanical allodynia and hyperalgesia in spared nerve injury (SNI)-induced and chronic constriction injury-induced pain. Its deficiency also greatly inhibited the excitability of nociceptive neurons. Interestingly, we found that suppressing HAP1 level diminished the membrane expression of the L-type calcium channel (Cav1.2), which can regulate Ca 2+ influx and then influence brain-derived neurotrophic factor (BDNF) synthesis and release. Furthermore, SNI-induced activation of astrocytes and microglia notably decreased in HAP1-deficient mice. These results indicate that HAP1 deficiency might attenuate pain responses. Collectively, our results suggest that HAP1 in dorsal horn and DRG neurons regulates Cav1.2 surface expression, which in turn reduces neuronal excitability, BDNF secretion, and inflammatory responses and ultimately influences neuropathic pain progression.

Exploring the Absorption Mechanisms of Imidazolium-Based Ionic Liquids to Epigallocatechin Gallate.

Imidazolium-based ionic liquids are wildly used in natural product adsorption and purification. In this work, one typical polymeric ionic liquid (PIL) was synthesized by using L-proline as the anion, which exhibited excellent adsorption capacity toward tea polyphenol epigallocatechin gallate (EGCG). The adsorption conditions were optimized with the response surface method (RSM). Under the optimum conditions, the adsorption capacity of the PIL for EGCG can reach as high as 552 mg/g. Dynamics and isothermal research shows that the adsorption process of EGCG by the PIL particularly meets the quasi-second-order kinetic equation and monolayer adsorption mechanism. According to thermodynamic parameter analysis, the adsorption process is endothermic and spontaneous. The results of theoretical calculation by molecular docking also demonstrated the interaction mechanisms between EGCG and the ionic liquid. Considering the wide application of imidazolium-based ionic liquids in component adsorption and purification, the present study can not only be extended to other similar experimental mechanism validation, but also be representative for guiding the synthesis of PIL and optimization of adsorption conditions.

Danhong injection attenuates doxorubicin-induced cardiotoxicity in rats via suppression of apoptosis: network pharmacology analysis and experimental validation.

Doxorubicin (DOX) is a potent chemotherapeutic agent that is used against various types of human malignancies. However, the associated risk of cardiotoxicity has limited its clinical application. Danhong injection (DHI) is a Chinese medicine with multiple pharmacological activities and is widely used for treating cardiovascular diseases. The aim of the present study was to evaluate the potential protective effect of DHI on DOX-induced cardiotoxicity in vivo and to investigate the possible underlying mechanisms. First, a sensitive and reliable HPLC-ESI-Q-TOF-MS/MS method was developed to comprehensively analyze the chemical compositions of DHI. A total of 56 compounds were identified, including phenolic acids, tanshinones, and flavonoids. Then, a DOX-induced chronic cardiotoxicity rat model was established to assess the therapeutic effect of DHI. As a result, DHI administration prevented the reduction in body weight and heart weight, and improved electrocardiogram performance. Additionally, the elevated levels of serum biochemical indicators were reduced, and the activities of oxidative enzymes were restored in the DOX-DHI group. Network pharmacology analysis further revealed that these effects might be attributed to 14 active compounds (e.g., danshensu, salvianolic acid A, salvianolic acid B, rosmarinic acid, and tanshinone IIA) and 15 potential targets (e.g., CASP3, SOD1, NOS3, TNF, and TOP2A). The apoptosis pathway was highly enriched according to the KEGG analysis. Molecular docking verified the good binding affinities between the active compounds and the corresponding apoptosis targets. Finally, experimental validation demonstrated that DHI treatment significantly increased the Bcl-2 level and suppressed DOX-induced Bax and caspase-3 expression in rat heart tissue. Furthermore, DHI treatment obviously decreased the apoptosis rate of DOX-treated H9c2 cells. These results indicate that DHI attenuated DOX-induced cardiotoxicity via regulating the apoptosis pathway. The present study suggested that DHI is a promising agent for the prevention of DOX-induced cardiotoxicity.

An analgesic peptide H-20 attenuates chronic pain via the PD-1 pathway with few adverse effects.

The lack of effective and safe analgesics for chronic pain management has been a health problem associated with people's livelihoods for many years. Analgesic peptides have recently shown significant therapeutic potential, as they are devoid of opioid-related adverse effects. Programmed cell death protein 1 (PD-1) is widely expressed in neurons. Activation of PD-1 by PD-L1 modulates neuronal excitability and evokes significant analgesic effects, making it a promising target for pain treatment. However, the research and development of small molecule analgesic peptides targeting PD-1 have not been reported. Here, we screened the peptide H-20 using high-throughput screening. The in vitro data demonstrated that H-20 binds to PD-1 with micromolar affinity, evokes Src homology 2 domain-containing tyrosine phosphatase 1 (SHP-1) phosphorylation, and diminishes nociceptive signals in dorsal root ganglion (DRG) neurons. Preemptive treatment with H-20 effectively attenuates perceived pain in naïve WT mice. Spinal H-20 administration displayed effective and longer-lasting analgesia in multiple preclinical pain models with a reduction in or absence of tolerance, abuse liability, constipation, itch, and motor coordination impairment. In summary, our findings reveal that H-20 is a promising candidate drug that ameliorates chronic pain in the clinic.

Non-Invasive Detection of Anti-Inflammatory Bioactivity and Key Chemical Indicators of the Commercial Lanqin Oral Solution by Near Infrared Spectroscopy.

Quality control methods of current traditional Chinese medicine (TCM) preparation is time-consuming and difficult to assess in terms of overall efficiency of the drug. A non-destructive rapid near-infrared spectroscopy detection system for key chemical components and biological activity of Lanqin oral solution (LOS), one of the best-selling TCM formulations, was established for comprehensive quality evaluation. Near infrared spectral scanning was carried out on 101 batches of commercial LOS under the penetrated vial state and traditional state. RAW 264.7 cells were cultured to detect the anti-inflammatory ability of LOS, and the reference concentrations of epigoitrin, geniposide, and baicalin were obtained by HPLC. The quantitative models were optimized by three kinds of variable selection methods. The correlation coefficients of prediction value of the models were greater than 0.94. The system also passed the external validation. The performance of the non-invasive models was similar to the traditional models. The established non-destructive system can be applied to the rapid quality inspection of LOS to avoid unqualified drugs from entering the market and ensure drug effectiveness. The biological activity index of LOS was introduced and predicted by NIRs for the first time, which provides a new idea about the quality control of TCM formulations.

Universal screening of 200 mycotoxins and their variations in stored cereals in Shanghai, China by UHPLC-Q-TOF MS.

Due to the challenge of hundreds of potential mycotoxins that may be present in cereals, a rapid and reliable ultra-high performance liquid chromatography coupled with quadrupole-time-of-flight tandem mass spectrometry (UHPLC-Q-TOF MS) technique was developed for universal screening of 200 mycotoxins (prototype, emerging and related derivatives) in cereals. With satisfactory sensitivity of accurate mass full-spectrum acquisition, it is feasible to preliminarily identify tentative untargeted mycotoxins with a large range of polarity without reference materials. The current screening method was also validated by the determination of 33 typical mycotoxins, and the screening detection limits in the range of 0.5-100 µg kg-1 were established in cereals. In total, 138 stored samples were contaminated by 46 mycotoxins and their metabolites, some of which were firstly reported in cereals, posing emerging potential health risks to humans and animals. Furthermore, the accumulation, transformation and degradation mechanisms of typical mycotoxins in cereals were investigated under real storage conditions.

[Application of near infrared spectroscopy to predict contents of various lactones in chromatographic process of Ginkgo Folium].

This study established a method for rapid quantification of terpene lactone, bilobalide, ginkgolide C, ginkgolide A and ginkgolide B in the chromatographic process of Ginkgo Folium based on near infrared spectroscopy(NIRS). The effects of competitive adaptive reweighting sampling(CARS), random frog(RF), and synergy interval partial least squares(siPLS) on the performance of partial least squares regression(PLSR) model were compared to the reference values measured by HPLC. Among them, the correlation coefficients of prediction(Rp) of validation sets of terpene lactone, bilobalide, and ginkgolide C were all higher than 0.98, and the relative standard errors of prediction(RSEPs) were 5.87%, 6.90% and 6.63%, respectively. Aiming at ginkgolide A and ginkgolide B with relatively low content, the genetic algorithm joint extreme learning machine(GA-ELM) was used to establish the optimized quantitative analysis model. Compared with CARS-PLSR model, the CARS-GA-ELM models of ginkgolide A and ginkgolide B exhibited a reduction in RSEP from 15.65% to 8.52% and from 21.28% to 10.84%, respectively, which met the needs of quantitative ana-lysis. It has been proved that NIRS can be used for the rapid detection of various lactone components in the chromatographic process of Ginkgo Folium.

Chemical composition analysis, antioxidant activity, and target cell-based screening of the potential active components in jujube and its fermented product.

In this study, the chemical constituents of jujube and jujube fermentation broth were compared by chromatography tandem high-resolution mass spectrometry for the first time. A total of 68 compounds were detected, and six of them were quantified. The results showed that rutin was hydrolyzed and converted into quercetin during the fermentation process. Further, the antioxidant experiments in vitro were carried out, and the IC50 value of the fermentation broth was lower than that of the jujube extract. Twenty-three potential bioactive components from jujube samples were identified by a target cell-based screening method, and triterpenic acid compounds exhibited high cell binding property. These results will help to understand the different biological activities of jujube and its fermented products and will benefit the discovery of new functional components.

Downregulation of Nck1 After Spinal Cord Injury in Adult Rats

Background: Nck1 is an important molecule that participates in many cellular processes, including neurite outgrowth, synaptic plasticity, and apoptosis. However, the expression and function of Nck1 in the spinal cord and spinal cord injury remain unknown. Aims: To investigate the role of Nck1 in spinal cord injury. Study Design: Animal experimentation. Methods: Adult Sprague­Dawley rats were used to establish an acute spinal cord injury model. Double immunofluorescence staining, Western blot, and quantitative reverse transcription polymerase chain reaction analysis were used to investigate the distribution, cellular localization, and expression of Nck1 in spinal cord injury processes. Short interfering RNA was used to silence Nck1 expression in VSC4.1 cells. The Shapiro­Wilk test was used for the normality distribution analysis; the Student's unpaired t-test, 1-way analysis of variance followed by post hoc Tukey's test were used for data analysis. Finally, RNA sequencing technology and gene ontology analysis were used to analyze the changes in Nck1-associated genes expression after spinal cord injury. Results: Colabeled staining demonstrated that Nck1 was especially distributed in neurons. Western blot, quantitative reverse transcription polymerase chain reaction, and statistical analysis revealed that Nck1 expression reduced to the lowest levels at 1 day after nerve injury, and slowly increased to a stable level in 21 days (P < .05). Nck1-specific short interfering RNA transfection significantly reduced cell viability and neurite development in neurons. Bioinformatic analysis indicated that Nck1 participates in multiple pathological processes of spinal cord injury, and many Nck1-associated genes exhibited differential expression levels. Conclusion: Nck1 is a vital protein in spinal cord injury processes and, therefore, further studies should be conducted to explore its potential functions and molecular mechanisms in spinal cord injury repair.

Rapid Determination of Geniposide and Baicalin in Lanqin Oral Solution by Near-Infrared Spectroscopy with Chemometric Algorithms during Alcohol Precipitation.

The selection of key variables is an important step that improves the prediction performance of a near-infrared (NIR) real-time monitoring system. Combined with chemometrics, NIR spectroscopy was employed to construct high predictive accuracy, interpretable models for the rapid detection of the alcohol precipitation process of Lanqin oral solution (LOS). The variable combination population analysis-iteratively retaining informative variables (VCPA-IRIV) was innovatively introduced into the variable screening process of the model of geniposide and baicalin. Compared with the commonly used synergy interval partial least squares regression, competitive adaptive reweighted sampling, and random frog, VCPA-IRIV achieved the maximum compression of variable space. VCPA-IRIV-partial least squares regression (PLSR) only needs to use about 1% of the number of variables of the original data set to construct models with Rp values greater than 0.95 and RMSEP values less than 10%. With the advantages of simplicity and strong interpretability, the prediction ability of the PLSR models had been significantly improved simultaneously. The VCPA-IRIV-PLSR models met the requirements of rapid quality detection. The real-time detection system can help researchers to understand the quality rules of geniposide and baicalin in the alcohol precipitation process of LOS and provide a reference for the optimization of a LOS quality control system.

Sodium Butyrate More Effectively Mitigates the Negative Effects of High-Concentrate Diet in Dairy Cows than Sodium ß-Hydroxybutyrate via Reducing Free Bacterial Cell Wall Components in Rumen Fluid and Plasma.

The present study was aimed at investigating the effects of sodium butyrate and sodium ß-hydroxybutyrate on lactation and health of dairy cows fed a high-concentrate (HC) diet. Eighty mid-lactation dairy cows with an average milk yield of 33.75 ± 5.22 kg/d were randomly allocated to four groups (n = 20 per group) and were fed either a low-concentrate (LC) diet, a HC diet, the HC diet with 1% sodium butyrate (HCSB), or the HC diet with 1% sodium ß-hydroxybutyrate (HCHB). The feeding trial lasted for 7 weeks, with a 2-week adaptation period and a 5-week measurement period, and the trial started from 96 ± 13 d in milk. Sodium butyrate supplementation delayed the decline in milk production and improved milk synthesis efficiency and milk fat content. Additionally, it decreased the proinflammatory cytokines and acute phase proteins (APPs) in plasma, the leucocytes in blood, the somatic cell count (SCC) in milk, and the gene expression of pattern recognition receptors (PRRs) and proinflammatory cytokines in the mammary gland, due to decreasing the contents of bacterial cell wall components (lipopolysaccharide, LPS; peptidoglycan, PGN; and lipoteichoic acid, LTA) in the rumen and plasma, compared with the HC diet. Sodium ß-hydroxybutyrate supplementation also improved milk yield, milk synthesis efficiency and milk fat content and partially reduced the adverse effects caused by the HC diet, but it had no effect on decreasing bacterial cell wall components in the rumen and plasma, compared with the HC diet. Collectively, both sodium butyrate and sodium ß-hydroxybutyrate mitigated the negative effects of HC diet on lactation and health of dairy cows, with sodium butyrate being more effective than sodium ß-hydroxybutyrate.

Algae-Derived Anti-Inflammatory Compounds against Particulate Matters-Induced Respiratory Diseases: A Systematic Review.

Air pollution has recently become a subject of increasing concern in many parts of the world. The World Health Organization (WHO) estimated that nearly 4.2 million early deaths are due to exposure to fine particles in polluted air, which causes multiple respiratory diseases. Algae, as a natural product, can be an alternative treatment due to potential biofunctional properties and advantages. This systematic review aims to summarize and evaluate the evidence of metabolites derived from algae as potential anti-inflammatory agents against respiratory disorders induced by atmospheric particulate matter (PM). Databases such as Scopus, Web of Science, and PubMed were systematically searched for relevant published full articles from 2016 to 2020. The main key search terms were limited to "algae", "anti-inflammation", and "air pollutant". The search activity resulted in the retrieval of a total of 36 publications. Nine publications are eligible for inclusion in this systematic review. A total of four brown algae (Ecklonia cava, Ishige okamurae, Sargassum binderi and Sargassum horneri) with phytosterol, polysaccharides and polyphenols were reported in the nine studies. The review sheds light on the pathways of particulate matter travelling into respiratory systems and causing inflammation, and on the mechanisms of actions of algae in inhibiting inflammation. Limitations and future directions are also discussed. More research is needed to investigate the potential of algae as anti-inflammatory agents against PM in in vivo and in vitro experimental models, as well as clinically.

[Rapid determination of active components in Ginkgo biloba leaves by near infrared spectroscopy combined with genetic algorithm joint extreme learning machine].

Near-infrared spectroscopy(NIRS) combined with band screening method and modeling algorithm can be used to achieve the rapid and non-destructive detection of the traditional Chinese medicine(TCM) production process. This paper focused on the ginkgo leaf macroporous resin purification process, which is the key technology of Yinshen Tongluo Capsules, in order to achieve the rapid determination of quercetin, kaempferol and isorhamnetin in effluent. The abnormal spectrum was eliminated by Mahalanobis distance algorithm, and the data set was divided by the sample set partitioning method based on joint X-Y distances(SPXY). The key information bands were selected by synergy interval partial least squares(siPLS); based on that, competitive adaptive reweighted sampling(CARS), successive projections algorithm(SPA) and Monte Carlo uninformative variable(MC-UVE) were used to select wavelengths to obtain less but more critical variable data. With selected key variables as input, the quantitative analysis model was established by genetic algorithm joint extreme learning machine(GA-ELM) algorithm. The performance of the model was compared with that of partial least squares regression(PLSR). The results showed that the combination with siPLS-CARS-GA-ELM could achieve the optimal model performance with the minimum number of variables. The calibration set correlation coefficient R_c and the validation set correlation coefficient R_p of quercetin, kaempferol and isorhamnetin were all above 0.98. The root mean square error of calibration(RMSEC), the root mean square error of prediction(RMSEP) and the relative standard errors of prediction(RSEP) were 0.030 0, 0.029 2 and 8.88%, 0.041 4, 0.034 8 and 8.46%, 0.029 3, 0.027 1 and 10.10%, respectively. Compared with the PLSR me-thod, the performance of the GA-ELM model was greatly improved, which proved that NIRS combined with GA-ELM method has a great potential for rapid determination of effective components of TCM.