Patients with cancer are prone to several debilitating side effects including fatigue, insomnia, depression and cognitive disturbances. Beetroot (Beta vulgaris L.) as a health promoting functional food may be potentially beneficial in cancer. As a source of polyphenols, flavonoids, dietary nitrates and other useful nutrients, beetroot supplementation may provide a holistic means to prevent cancer and manage undesired effects associated with chemotherapy. The main aim of this narrative review is to discuss beetroot’s nutrient composition, current studies on its potential utility in chemoprevention and cancer-related fatigue or treatment-related side effects such as cardiotoxicity. This review aims to provide the current status of knowledge and to identify the related research gaps in this area. The flavonoids and polyphenolic components present in abundance in beetroot support its significant antioxidant and anti-inflammatory capacities. Most in vitro and in vivo studies have shown promising results; however, the molecular mechanisms underlying chemopreventive and chemoprotective effects of beetroot have not been completely elucidated. Although recent clinical trials have shown that beetroot supplementation improves human performance, translational studies on beetroot and its functional benefits in managing fatigue or other symptoms in patients with cancer are still lacking.

Patients with cancer are prone to several debilitating side effects including fatigue, insomnia, depression and cognitive disturbances. Beetroot (Beta vulgaris L.) as a health promoting functional food may be potentially beneficial in cancer. As a source of polyphenols, flavonoids, dietary nitrates and other useful nutrients, beetroot supplementation may provide a holistic means to prevent cancer and manage undesired effects associated with chemotherapy. The main aim of this narrative review is to discuss beetroot’s nutrient composition, current studies on its potential utility in chemoprevention and cancer-related fatigue or treatment-related side effects such as cardiotoxicity. This review aims to provide the current status of knowledge and to identify the related research gaps in this area. The flavonoids and polyphenolic components present in abundance in beetroot support its significant antioxidant and anti-inflammatory capacities. Most in vitro and in vivo studies have shown promising results; however, the molecular mechanisms underlying chemopreventive and chemoprotective effects of beetroot have not been completely elucidated. Although recent clinical trials have shown that beetroot supplementation improves human performance, translational studies on beetroot and its functional benefits in managing fatigue or other symptoms in patients with cancer are still lacking.

With the advent of Twenty-First century, more and more genome-wide association studies (GWAS) showed that idiosyncratic adverse drug reactions (ADRs) were closely related with human leukocyte antigen (HLA) alleles, such as the associations of abacavir-HLA-B*5701, allopurinol-HLA-B*5801, and carbamazepine-HLA-B*1502, etc. To explore the mechanisms of these idiosyncratic drug reactions, hapten hypothesis, danger signal hypothesis, pharmacological interaction (P-I) concept and autoimmune mechanism are proposed. In this paper, recent GWAS studies on the HLA-mediated adverse drug reactions and underlying mechanism are reviewed in detail.
Alleles ; Allopurinol ; adverse effects ; Anti-HIV Agents ; adverse effects ; Anticonvulsants ; adverse effects ; Carbamazepine ; adverse effects ; Dideoxynucleosides ; adverse effects ; Drug Hypersensitivity Syndrome ; etiology ; immunology ; Drug-Related Side Effects and Adverse Reactions ; genetics ; immunology ; Enzyme Inhibitors ; adverse effects ; Genome-Wide Association Study ; HLA Antigens ; genetics ; HLA-B Antigens ; immunology ; HLA-B15 Antigen ; immunology ; Humans ; Stevens-Johnson Syndrome ; etiology ; immunology

Objective To explore the dosage and injection method of concanavalin A(Con A) for inducing Wistar rats into the acute hepatic injury model. Methods (1)According to the dosage of Con A, 42 Wistar rats were randomly divided into groups A, B, C, D, E, N, 7 rats in each group. Group N was given tail intravenous injection of normal saline as normal control group. Groups A, B, C, D, E were given intravenous injection of 4, 8, 16, 30, 40 mg/kg of Con A respectively. At the 8th hour after modeling, the levels of alanine transaminase(ALT), aspartate aminotransferase(AST), albumin(ALB), interleukin(IL)-2 , IL-10, interferon (IFN)-γ, and tumor necrosis factor(TNF)-αwere detected. And HE staining was used to observe the pathological feature of hepatic tissue. (2)According to the injection method of Con A, 21 Wistar rats were randomly divided into normal control group, intraperitoneal injection group and tail intravenous injection group, 7 rats in each group. The dosage of Con A for the rats in intraperitoneal injection group and tail intravenous injection group was 16 mg/kg. At the 8th hour after modeling, the levels of serum ALT, AST, and ALB were determined. Results The number of abnormal deaths in various dose Con A groups at the end of each experiment was 0 in groups A, B, C, and 2 in group D, and 7 in group E. A small amount of spotty necrosis, inflammatory cell infiltration, and hepatic lobule with almost integrity of structure were found in groups A, B, while obvious bridging-like necrosis was seen in groups C, D. Serum ALT, AST, and ALB levels in intraperitoneal injection group had no statistically significant difference as compared with the normal control group. Conclusion Tail intravenous injection of 16 mg/kg of Con A can be used to induce an acute immunological liver injury rat model successfully.

Objective:To observe the effect of electroacupuncture (EA) pretreatment on adenine nucleotides in the myocardial tissues of the myocardial ischemia-reperfusion injury (MIRI) rats, and to explore the mechanism of EA pretreatment on myocardial prevention and protection in MIRI rats. Methods:Forty SPF male Sprague-Dawley (SD) rats were randomly divided into 5 groups: a blank group, a sham operation group, a model group, an EA at Neiguan (PC 6) group and an EA at Hegu (LI 4) group, with 8 rats in each group. Rats in the blank group only received binding to the rat plate, 30 min/time, once a day for 7 d; on the 7th day, rats in the sham operation group were subjected to threading for 40 min at the left anterior descending coronary artery without ligation, and then the rats were allowed to stand for 60 min before collection of the specimens; on the 7th day, rats in the model group were subjected to threading at the left anterior descending coronary artery with ligation, for 40 min before the blood flow was restored, and then the rats were allowed to stand for 60 min before collection of the specimens; on the 7th day of pretreatment with EA at Neiguan (PC 6) or Hegu (LI 4) for 30 min per day (once a day for 7 d), rats in the EA at Neiguan (PC 6) group and EA at Hegu (LI 4) group were subjected to modeling and sample collection same as in the model group. The left ventricular myocardium of the lower left anterior descending coronary artery was collected from rats in all 5 groups. Hematoxylin-eosin (HE) staining and transmission electron microscope (TEM) were used to observe the changes in myocardial pathological morphology. The change in the adenine nucleotide level of myocardial tissue was measured by high performance liquid chromatography (HPLC). Results:The HE staining and ultrastructure showed that the myocardial injury was severer in the model group compared with the sham operation group. Compared with the model group, the myocardial injury in the EA at Neiguan (PC 6) and the EA at Hegu (LI 4) groups was mild or hardly any. The adenine nucleotide levels in the sham operation group and the model group were all decreased compared with the blank group (allP<0.05); compared with the sham operation group, the adenine nucleotide level of the model group was also decreased, but the difference was not statistically significant (P>0.05); compared with the model group, the adenine nucleotide level in the EA at Neiguan (PC 6) group was increased (P<0.05), and the adenine nucleotide level in the EA at Hegu (LI 4) group was significantly increased (P<0.01). The adenine nucleotide level in the EA at Hegu (LI 4) group was higher than that in the EA at Neiguan (PC 6) group, but the difference was not statistically significant (P>0.05). Compared with the EA at Neiguan (PC 6) group, the levels of adenosine triphosphate (ATP), adenosine diphosphate (ADP) and adenosine monophosphate (AMP) in the EA at Hegu (LI 4) group were significantly increased (allP<0.01). Conclusion:Both EA at Neiguan (PC 6) and Hegu (LI 4) can alleviate the pathological damage to myocardium in MIRI rats, and increase the adenine nucleotide level in myocardial tissues, and thus protect MIRI rats. EA at Hegu (LI 4) has a better protective effect than Neiguan (PC 6).

OBJECTIVE: To investigate the role of microglial pyroptosis in hypoxic-ischemic brain damage. METHODS: An oxygen-glucose deprivation/reoxygenation (OGD/R) model of rat microglial cells were cultured in vitro. Western blot was used to measure the expression of the pyroptosis-related proteins caspase-1, interleukin-1β (IL-1β), and N-terminal gasdermin D (GSDMD-N) at 0, 1, 3, 6, 12, and 24 hours after OGD/R. After the microglial cells were transfected with lentivirus-mediated silenced gasdermin D (GSDMD), immunofluorescence assay and Western blot were used to measure the transfection rate of GSDMD. Microglial cell lines were divided into three groups: normal control, negative control, and LV-sh_GSDMD (lentivirus-mediated GSDMD silencing). CCK-8 assay and LDH kit were used to observe the effect of GSDMD silencing on the viability and toxicity of microglial cells at 24 hours after OGD/R. Western blot was used to observe the effect of GSDMD silencing on the levels of caspase-1, GSDMD-N, and IL-1β in the microglial cells at 24 hours after OGD/R. RESULTS: The expression levels of the pyroptosis-related proteins caspase-1, GSDMD-N, and IL-1β in microglial cells were upregulated since 0 hour after OGD/R and reached the peak levels at 24 hours. A microglial cell model of lentivirus-mediated GSDMD silencing was successfully constructed. At 24 hours after OGD/R, compared with the normal control group, the GSDMD silencing group had a significant increase in the cell viability and a significant reduction in the cytotoxicity (P<0.05), as well as significant reductions in the protein expression levels of caspase-1, GSDMD-N, and IL-1β in microglial cells (P<0.05). CONCLUSIONS Lentivirus silencing of the key substrate protein for pyroptosis GSDMD can alleviate hypoxic-ischemic brain damage, suggesting that microglial pyroptosis aggravates hypoxic-ischemic brain damage.
Animals ; Brain/metabolism* ; Intracellular Signaling Peptides and Proteins ; Microglia/metabolism* ; Pyroptosis ; Rats

OBJECTIVETo investigate the effects of prebiotics supplementation for 9 days on gut microbiota structure and function and establish a machine learning model based on the initial gut microbiota data for predicting the variation of Bifidobacterium after prebiotic intake.

METHODSWith a randomized double-blind self-controlled design, 35 healthy volunteers were asked to consume fructo-oligosaccharides (FOS) or galacto-oligosaccharides (GOS) for 9 days (16 g per day). 16S rRNA gene high-throughput sequencing was performed to investigate the changes of gut microbiota after prebiotics intake. PICRUSt was used to infer the differences between the functional modules of the bacterial communities. Random forest model based on the initial gut microbiota data was used to identify the changes in Bifidobacterium after 5 days of prebiotic intake and then to build a continuous index to predict the changes of Bifidobacterium. The data of fecal samples collected after 9 days of GOS intervention were used to validate the model.

RESULTSFecal samples analysis with QIIME revealed that FOS intervention for 5 days reduced the intestinal flora alpha diversity, which rebounded on day 9; in GOS group, gut microbiota alpha diversity decreased progressively during the intervention. Neither FOS nor GOS supplement caused significant changes in β diversity of gut microbiota. The area under the curve (AUC) of the prediction model was 89.6%. The continuous index could successfully predict the changes in Bifidobacterium (R=0.45, P=0.01), and the prediction accuracy was verified by the validation model (R=0.62, P=0.01).

CONCLUSIONShort-term prebiotics intervention can significantly decrease α-diversity of the intestinal flora. The machine learning model based on initial gut microbiota data can accurately predict the changes in Bifidobacterium, which sheds light on personalized nutrition intervention and precise modulation of the intestinal flora.

OBJECTIVETo study the effect of Tongxinluo superfine (TXL) on experimental anginal model induced by Arginine Vasopressin in rats with endothelial dysfunction.

METHODFirst, the endothelial dysfunction rat model was made by methionine-induced hyperhomocysteinemia (HHcy). The thoracic aorta were excised, and acetylcholine (Ach)-induced endothelium dependent relaxation and sodium nitroprusside (SNP) induced endothelium-independent relaxation were measured. Total plasma homocysteine (Hcy) concentrations were measured with automated fluorescence polarization immunoassay (FPIA). Enzyme-linked immunosorbent assay (ELISA) was used to detect plasma von Willebrand factor (vWF) level. Plasma nitric oxide (NO) contents were assayed by method of nitrate reductase. Then, the rat model of collaterals contraction (model group) was established by AVP intravenous injection in rats with endothelial dysfunction and the S wave change (DeltaS) and T wave depression in Lead II ECG were used as the index of angina severity. The nitric oxide (NO) contents in serum and the expression of myocardium eNOS mRNA were measured.

RESULTAch (0. 1-1000 nmol L(-1))-induced endothelium dependent relaxation (EDR) of aortic rings was significantly decreased in HHcy group. The endothelium-independent relaxation induced by SNP (0.001-10 micromol L(-1)) was not significantly different between the two groups. Plasma homocysteine concentrations and vWF levels in rats treated with methionine were higher than those of control group, while NO contents were significantly decreased in HHcy group compared with control. The results showed that L-methionine intake induced hyperhomocysteinemia in rats. Impaired EDR, increased vWF and decreased NO suggested the exist of endothelial dysfunction. DeltaS of model group increased from 1 min to 5 min and T wave of model group depressed at 2 min compared with that of control after the administration of vasopressin (0.5 U kg(-1)). The intragastric administration of TXL inhibited vasopressin-induced S wave change at 4 min and 5 min and T wave depression from 30 s to 3 min after AVP injection. The NO contents in serum and the expression of myocardium eNOS mRNA of TXL group were increased compared with model group.

CONCLUSIONExperimental angina induced by AVP injection is more severe in rats with endothelial dysfunction. Tongxinluo Superfine can protect against collaterals contraction in rats maybe by increasing the NO contents in serum and the expression of myocardium eNOS mRNA.

Acetylcholine ; pharmacology ; Animals ; Aorta, Thoracic ; drug effects ; physiopathology ; Drug Combinations ; Drugs, Chinese Herbal ; administration & dosage ; isolation & purification ; pharmacology ; Electrocardiography ; Endothelium, Vascular ; drug effects ; physiopathology ; Enzyme-Linked Immunosorbent Assay ; Hyperhomocysteinemia ; metabolism ; physiopathology ; In Vitro Techniques ; Male ; Myocardial Ischemia ; blood ; genetics ; physiopathology ; Myocardium ; metabolism ; pathology ; Nitric Oxide ; blood ; Nitric Oxide Synthase Type III ; biosynthesis ; genetics ; Nitroprusside ; pharmacology ; Plants, Medicinal ; chemistry ; RNA, Messenger ; genetics ; metabolism ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Reverse Transcriptase Polymerase Chain Reaction ; Vasodilation ; drug effects ; Vasodilator Agents ; pharmacology ; von Willebrand Factor ; metabolism

Objective To investigate the effect of hot spring baths on human immune function by analyzing the changes of immunoglobulins and complements in serum of residents after hot spring baths in order to provide a theoretical reference for the therapeutic effect of hot spring bathing. Methods After physical examination, 421 volunteers from five hot spring areas with three types of hot springs(temperature type hot springs, metasilicic acid type hot springs, and warm mineral spring type hot springs)in Guizhou Province were selected as the subjects. Under the guidance of professionals, the volunteers took a hot spring bath with the whole body immersed for four weeks, once a day, 5 times a week and 40-50 minutes each time. Finally, 311 volunteers completed the standard bath required by this study. The transmission immunoturbidimetric method was used to determine the content of immunoglobulins reflecting mucosal anti-infective immunity(IgA), anti-pathogenic microorganisms(IgG), recent infections(IgM)and the level of important immune effect factors(C3, C4)in the serum. Paired T test was used to compare the changes of serum immunoglobulin and complement before and after the hot spring bath therapy. Results Before the hot spring baths, the content of serum IgG, IgA, IgM, and complements C3 and C4 was(12.169±2.358)g/L, (2.285±0.891)g/L, (1.430±0.660)g/L, (1.224±0.186)g/L, and(0.257±0.073)g/L, respectively. After the hot spring baths, the content of serum IgG, IgA, IgM, and complements C3 and C4 was(12.769±2.984)g/L, (2.397±0.909)g/L, (1.497±0.715)g/L, (1.242±0.169)g/L, and(0.266±0.074)g/L, respectively.Comparison of results of different types of hot springs showed that warm mineral type of hot springs and metasilicic acid type of hot springs could significantly increase the serum levels of main immunoglobulins IgG and IgA(P < 0.05), while water temperature type of hot springs could increase the serum IgA content of the population(P < 0.05), but the effect on IgG was not significant(P > 0.05). Compared with before the bath intervention, the level of complement C4 in the serum increased in the population after the intervention of metasilicic acid type of hot springs and water temperature type of hot springs(P < 0.05). Conclusion Hot spring bathing can enhance the body's humoral immune function. Given that IgG is the most important anti-pathogenic microorganism antibody in body fluids, the result suggests that metasilicic acid hot spring and warm mineral hot spring are better than pure water temperature hot spring in terms of improving the body's humoral immune function.

Tyrosine kinase inhibitors(TKIs)have emerged as the first-line small molecule drugs in many cancer therapies,exerting their effects by impeding aberrant cell growth and proliferation through the mod-ulation of tyrosine kinase-mediated signaling pathways.However,there exists a substantial inter-individual variability in the concentrations of certain TKIs and their metabolites,which may render patients with compromised immune function susceptible to diverse infections despite receiving theo-retically efficacious anticancer treatments,alongside other potential side effects or adverse reactions.Therefore,an urgent need exists for an up-to-date review concerning the biological matrices relevant to bioanalysis and the sampling methods,clinical pharmacokinetics,and therapeutic drug monitoring of different TKIs.This paper provides a comprehensive overview of the advancements in pretreatment methods,such as protein precipitation(PPT),liquid-liquid extraction(LLE),solid-phase extraction(SPE),micro-SPE(p-SPE),magnetic SPE(MSPE),and vortex-assisted dispersive SPE(VA-DSPE)achieved since 2017.It also highlights the latest analysis techniques such as newly developed high performance liquid chromatography(HPLC)and high-resolution mass spectrometry(HRMS)methods,capillary electro-phoresis(CE),gas chromatography(GC),supercritical fluid chromatography(SFC)procedures,surface plasmon resonance(SPR)assays as well as novel nanoprobes-based biosensing techniques.In addition,a comparison is made between the advantages and disadvantages of different approaches while pre-senting critical challenges and prospects in pharmacokinetic studies and therapeutic drug monitoring.