ABSTRACT
OBJECTIVES: Observational studies have suggested that a higher 25-hydroxyvitamin D concentration may be associated with longer telomere length; however, this has not been investigated in randomised controlled trials. We conducted an ancillary study within a randomised, double-blind, placebo-controlled trial of monthly vitamin D (the D-Health Trial) for the prevention of all-cause mortality, conducted from 2014 to 2020, to assess the effect of vitamin D supplementation on telomere length (measured as the telomere to single copy gene (T/S) ratio). DESIGN, SETTING, PARTICIPANTS, AND INTERVENTION: Participants were Australians aged 60-84 years and we randomly selected 1,519 D-Health participants (vitamin D: n=744; placebo: n=775) for this analysis. We used quantitative polymerase chain reaction to measure the relative telomere length (T/S ratio) at 4 or 5 years after randomisation. We compared the mean T/S ratio between the vitamin D and placebo groups to assess the effect of vitamin D supplementation on relative telomere length, using a linear regression model with adjustment for age, sex, and state which were used to stratify the randomisation. RESULTS: The mean T/S ratio was 0.70 for both groups (standard deviation 0.18 and 0.16 for the vitamin D and placebo groups respectively). The adjusted mean difference (vitamin D minus placebo) was -0.001 (95% CI -0.02 to 0.02). There was no effect modification by age, sex, body mass index, or predicted baseline 25-hydroxyvitamin D concentration. CONCLUSION: In conclusion, routinely supplementing older adults, who are largely vitamin D replete, with monthly doses of vitamin D is unlikely to influence telomere length.
Subject(s)
Vitamin D , Vitamins , Humans , Aged , Australia , Vitamins/pharmacology , Vitamins/therapeutic use , Calcifediol , Telomere , Dietary Supplements , Randomized Controlled Trials as TopicABSTRACT
BACKGROUND: Recovery of high-purity tea saponin (TS), a promising non-ionic surfactant with well-documented properties, is one of the major challenges to broadening its industrial applications. In this study, an innovative and sustainable strategy for the highly-efficient purification of TS was developed by using well-designed highly-porous polymeric adsorbents. RESULTS: The prepared Pp-A with controllable macropores (~96 nm) and appropriate surface hydrophobic properties was found more favorable for achieving high adsorption efficiency towards TS/TS-micelles. Kinetic results showed the adsorption follows the pseudo-second-order model (R2 = 0.9800), and the Langmuir model is more qualified to explicate the adsorption isotherms with Qe-TS ~ 675 mg g-1 . Thermodynamic studies revealed the monolayer adsorption of TS was an endothermic process that was conducted spontaneously. Interestingly, ethanol-driven desorption (90% v/v ethanol) of TS was rapidly (< 30 min) complete due to the possible ethanol-mediated disassembling of TS-micelles. A possible mechanism that involves the interactions between the adsorbents and TS/TS-micelles, the formation and disassembling of TS-micelles was proposed to account for the highly efficient purification of TS. Afterwards, Pp-A-based adsorption method was developed to purify TS directly from industrial camellia oil production. Through selective adsorption, pre-washing, and ethanol-driven desorption, the applied Pp-A enabled the direct isolation of high-purity TS (~96%) with a recovery ratio > 90%. Notably, Pp-A exhibited excellent operational stability and is of high potential for long-term industrial application. CONCLUSION: Results ensured the practical feasibility of the prepared porous adsorbents in purifying TS, and the proposed methodology is a promising industrial-scale purification strategy. © 2023 Society of Chemical Industry.
Subject(s)
Camellia , Saponins , Water Pollutants, Chemical , Water Purification , Camellia/chemistry , Porosity , Micelles , Polymers , Adsorption , Tea/chemistry , Ethanol , Kinetics , Water Pollutants, Chemical/chemistry , Water Purification/methodsABSTRACT
Background: Tourette syndrome (TS) is a complex neurodevelopmental disorder characterized by vocal and motor tics. Recurrent respiratory tract infection (RRTI), a commonly occurring disease in childhood, correlates with recurrent and severe course of tic symptoms. Qiangzhi decoction (QZD) is a traditional Chinese medicine that can alleviate TS symptoms while reducing the recurrence of RRTI. However, the mechanism of QZD on TS and RRTI remains unclear. This study aimed to determine the treatment effect of QZD on comorbid TS and RRTI by integrating ultrahigh-performance liquid chromatography mass spectrometry (UPLC-MS), network pharmacology, and intestinal flora analysis. Methods: The components of QZD were first identified by UPLC-quadrupole (Q)-orbitrap-MS/MS. The mechanism of QZD on comorbid RRTI and TS was investigated by a series of network pharmacological methods, including target prediction and bioinformatics analysis. Finally, a comorbid TS and RRTI rat model was established by intraperitoneal injection of 3,3-iminodipropionitrile (IDPN), cyclophosphamide (CTX), and lipopolysaccharide (LPS). Alteration of gut microbiota in the alleviation of TS and RRTI by QZD was investigated via intestinal flora analysis. Results: The results of UPLC-Q-orbitrap-MS/MS showed that QZD had 96 types of chemical components. The network pharmacology results demonstrated that targets of QZD involved in the treatment of TS and RRTI involved 1045 biological processes (BPs), 109 cellular components (CCs), and 133 molecular functions (MFs), including synaptic and transsynaptic signaling, chemical synaptic transmission, neurotransmitter receptor activity, G protein-coupled amine receptor activity, and serotonin receptor activity, among others. Firmicutes, Bacteroidetes, Coprococcus, and Lachnospiraceae played crucial roles in gut microbiota of a QZD-treated comorbid TS and RRTI model. Conclusions: Our results revealed QZD provided a multicomponent, multitarget, and multipathway synergistic treatment of comorbid TS and RRTI.
ABSTRACT
Pyridoxal 5'-phosphate (PLP), the catalytically active form of vitamin B6, participates as a cofactor to one carbon (1C) pathway that produces precursors for DNA metabolism. The concerted action of PLP-dependent serine hydroxymethyltransferase (SHMT) and thymidylate synthase (TS) leads to the biosynthesis of thymidylate (dTMP), which plays an essential function in DNA synthesis and repair. PLP deficiency causes chromosome aberrations (CABs) in Drosophila and human cells, rising the hypothesis that an altered 1C metabolism may be involved. To test this hypothesis, we used Drosophila as a model system and found, firstly, that in PLP deficient larvae SHMT activity is reduced by 40%. Second, we found that RNAi-induced SHMT depletion causes chromosome damage rescued by PLP supplementation and strongly exacerbated by PLP depletion. RNAi-induced TS depletion causes severe chromosome damage, but this is only slightly enhanced by PLP depletion. dTMP supplementation rescues CABs in both PLP-deficient and PLP-proficient SHMTRNAi . Altogether these data suggest that a reduction of SHMT activity caused by PLP deficiency contributes to chromosome damage by reducing dTMP biosynthesis. In addition, our work brings to light a gene-nutrient interaction between SHMT decreased activity and PLP deficiency impacting on genome stability that may be translated to humans.
Subject(s)
Chromosome Aberrations , Glycine Hydroxymethyltransferase , Vitamin B 6 , Animals , Humans , DNA , Drosophila/metabolism , Glycine Hydroxymethyltransferase/metabolism , Pyridoxal Phosphate , Thymidine Monophosphate/biosynthesis , Vitamin B 6/pharmacologyABSTRACT
Assessment of river water quality is very important for understanding the impact of human activities on aquatic ecosystems. As the second-largest river in China, the Yellow River's water environment is closely related to the social development and water security of northern China. The Huangshui River is a major tributary of the upper Yellow River, and it supplies water to cities in the lower reaches. In this study, a Takagi-Sugeno (T-S) fuzzy neural network was used to evaluate water quality of the Huangshui River, and pollutant sources were analyzed. The heavy metal pollution index (HPI) was calculated to assess the heavy metal pollution level, and the health risks posed by heavy metal elements were assessed. The results indicated that the main contaminants in the Huangshui River were ammonia nitrogen (NH3-N) and total phosphorus (TP), which was affected by various activities of industry, agriculture, and urbanization, and the maximum concentration of NH3-N and TP was 5.90 mg/L and 0.36 mg/L, respectively. The T-S evaluation results of some points in the middle reaches were 3.317 and 3.197, which belonged to Level â £ and the water quality was poor. The concentrations of Cu, Zn and Cr in the river were 0.57-44.58 µg/L, 10-122.50 µg/L and 2-28.67 µg/L, respectively, and they were relatively large. The T-S fuzzy neural network could evaluate water quality, avoiding extreme evaluation results by using fuzzy rules to reduce the influence of pollutant concentrations that are too high or too low. In addition to qualitative categorization of water quality, this approach can also quantitatively assess water quality within a single category. The results of water quality assessment could provide a scientific data support for river management.
Subject(s)
Metals, Heavy , Water Pollutants, Chemical , China , Ecosystem , Environmental Monitoring/methods , Geologic Sediments , Humans , Metals, Heavy/analysis , Neural Networks, Computer , Phosphorus/analysis , Risk Assessment , Rivers , Water Pollutants, Chemical/analysis , Water QualityABSTRACT
The discovery of a bioactive inhibitor tool for human polypeptide N-acetylgalactosaminyl transferases (GalNAc-Ts), the initiating enzyme for mucin-type O-glycosylation, remains challenging. In the present study, we identified an array of quinic acid derivatives, including four new glycerates (1-4) from Tussilago farfara, a traditional Chinese medicinal plant, as active inhibitors of GalNAc-T2 using a combined screening approach with a cell-based T2-specific sensor and purified enzyme assay. These inhibitors dose-dependently inhibited human GalNAc-T2 but did not affect O-linked N-acetylglucosamine transferase (OGT), the other type of glycosyltransferase. Importantly, they are not cytotoxic and retain inhibitory activity in cells lacking elongated O-glycans, which are eliminated by the CRISPR/Cas9 gene editing tool. A structure-activity relationship study unveiled a novel quinic acid-caffeic acid conjugate pharmacophore that directs inhibition. Overall, these new natural product inhibitors could serve as a basis for developing an inhibitor tool for GalNAc-T2.
Subject(s)
Enzyme Inhibitors/pharmacology , N-Acetylgalactosaminyltransferases/antagonists & inhibitors , Quinic Acid/pharmacology , Tussilago/chemistry , Cells, Cultured , Dose-Response Relationship, Drug , Enzyme Inhibitors/chemistry , Enzyme Inhibitors/metabolism , Flowers/chemistry , Flowers/metabolism , Glycosylation , HEK293 Cells , Humans , Molecular Conformation , N-Acetylgalactosaminyltransferases/isolation & purification , N-Acetylgalactosaminyltransferases/metabolism , Quinic Acid/chemistry , Quinic Acid/metabolism , Structure-Activity Relationship , Tussilago/metabolism , Polypeptide N-acetylgalactosaminyltransferaseABSTRACT
Rising worldwide demand and consumption of fossil fuels have elevated wealth creation, improved undesirable impacts on climatic change from emission of greenhouse gases, and endangered communal health. In developing nations, biomass wastes, which include but are not limited to agricultural residues, are generated in huge quantities yearly. During the disposal of biomass, incomplete combustion causes people to get exposed to elevated indoor concentrations on health-damaging pollutants including particulate matter and carbon monoxide. Inefficient usage or disposed biomass wastes may cause toxic impacts on higher levels of pollution, the consequent degeneration of public health and ecological contamination. It is possible to convert these wastes into energy-efficient briquettes through densification. In this research work, the combustion characteristics were identified from biomass briquettes which were produced from Onion Peels (OP), Tamarind Shells (TS) and Cassava Starch. OP-TS were mixed sequentially and conversely with different proportions. From the total weight of biomass, 10% of cassava starch was added and briquettes were produced under 200 kN pressure from the compressed hydraulic system within the dwell time of 60 seconds. The proximate characteristics such as the presence of water content, amount of fixed carbon, ash and volatile matter were determined by using the standard procedures of the American Society for Testing and Materials (ASTM). The ultimate parameter, which is inclusive of Carbon (C), Hydrogen (H) and Oxygen (O) were diagnosed in all produced biomass briquettes and calorific values were identified for all the produced biomass briquettes as well. OP-TS have better fuel properties in comparison with pine, cotton stalk (CS), wood sawdust (WS), municipal solid waste (MSW) and cotton straw biomass briquettes (CSB). Therefore, the produced biomass briquettes could bring substantial environmental and socio-economic benefits to rural communities and are potentially worthy fuels derived from agricultural wastes.
Subject(s)
Onions , Tamarindus , Biomass , Humans , Starch , WoodABSTRACT
Down syndrome (DS), a major genetic cause of intellectual disability, is characterized by numerous neurodevelopmental defects. Previous in vitro studies highlighted a relationship between bioenergetic dysfunction and reduced neurogenesis in progenitor cells from the Ts65Dn mouse model of DS, suggesting a critical role of mitochondrial dysfunction in neurodevelopmental alterations in DS. Recent in vivo studies in Ts65Dn mice showed that neonatal supplementation (Days P3-P15) with the polyphenol 7,8-dihydroxyflavone (7,8-DHF) fully restored hippocampal neurogenesis. The current study was aimed to establish whether brain mitochondrial bioenergetic defects are already present in Ts65Dn pups and whether early treatment with 7,8-DHF positively impacts on mitochondrial function. In the brain and cerebellum of P3 and P15 Ts65Dn pups we found a strong impairment in the oxidative phosphorylation apparatus, resulting in a deficit in mitochondrial ATP production and ATP content. Administration of 7,8-DHF (dose: 5 mg/kg/day) during Days P3-P15 fully restored bioenergetic dysfunction in Ts65Dn mice, reduced the levels of oxygen radicals and reinstated the hippocampal levels of PGC-1α. No pharmacotherapy is available for DS. From current findings, 7,8-DHF emerges as a treatment with a good translational potential for improving mitochondrial bioenergetics and, thus, mitochondria-linked neurodevelopmental alterations in DS.
ABSTRACT
BACKGROUND: Tourette's syndrome (TS) is a neurodevelopmental condition characterized by multiple motor and vocal tics. Qiangzhi decoction (QD), a well-known herbal decoction, has been used in treating TS in China for decades. We have found relevance between the indications of QD and the classic symptoms of TS. The pharmacological mechanisms of QD in treating TS are still unclear. METHODS: The active compounds of QD were extracted from multi-database, including TCMSP (the Traditional Chinese Medicine Systems Pharmacology database), and potential targets of the compounds were compiled by target fishing. The TS target database was established, and then the protein-protein interaction (PPI) network was constructed to analyze the interactions between the potential targets of compounds in QD and targets associated with TS and screened the core targets by topology. The DAVID bioinformatics database was used to conduct the Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. RESULTS: 59 active molecules and 585 potential targets of QD were selected. The consequences of the DAVID enrichment analysis show that 36 cellular biological processes (FDR <0.01) and 65 pathways (FDR <0.01) of QD chiefly took part in the convoluted treating effects relevant to the dopamine system, inflammation, and infection, and miRNA pathway. Fourteen core targets of QD were found as potential targets of the treatment of TS. CONCLUSIONS: QD could relieve the symptoms of TS through the molecular mechanisms predicted by network pharmacology. This study supplies insight into how network pharmacology can predict traditional Chinese herbal medicine's possible molecular mechanisms (TCHM).
Subject(s)
Drugs, Chinese Herbal , Tourette Syndrome , China , Drugs, Chinese Herbal/therapeutic use , Humans , Medicine, Chinese Traditional , Tourette Syndrome/drug therapyABSTRACT
Tourette's syndrome (TS) is an inherited neurologic disorder characterized by involuntary stereotyped motor and vocal tics. Its pathogenesis is still unclear and its treatment remains limited. Recent research has suggested the involvement of immune mechanisms in the pathophysiology of TS. Microglia are the brain's resident innate immune cells. They can mediate neuroinflammation and regulate brain development and homeostasis. A traditional Chinese medicine (TCM), Ningdong granule (NDG), has been found to be efficacious in the treatment of TS while causing few adverse reactions. In the current study, a rat model of 3,3'-iminodipropionitrile (IDPN)-induced TS was used to explore the regulating effects and mechanisms of NDG on microglia-mediated neuroinflammation. IDNP led to robust pathological changes and neurobehavioral complications, with activation of microglia in the striatum of rats with TS. After activation by IDNP, microglia strongly responded to this specific injury, and TNF-α, IL-6, and MCP-1 were released in the striatum and/or serum of rats with TS. Interestingly, NDG inhibited the activation of microglia and decreased the abnormal expression of TNF-α, IL-6, and MCP-1 in the striatum and/or serum of rats with TS, thus controlling tics. However, there were no significant changes in the striatum and/or serum of rats with TS after treatment with haloperidol. The anti-TS action of haloperidol might occur not through microglial activation and neuroinflammation but through the DAT system, thus controlling tics. In conclusion, microglia might play key roles in mediating neuroinflammatory responses in TS, triggering the release of TNF-α, IL-6, and MCP-1.NDG inhibited tics in rats with TS, and this mechanism may be associated with a reduction in the increased number of activated microglia and a decrease in the expression of pro-inflammatory cytokines and chemokines in the striatum and/or serum.
Subject(s)
Corpus Striatum/drug effects , Drugs, Chinese Herbal/pharmacology , Microglia/drug effects , Tourette Syndrome/drug therapy , Animals , Chemokine CCL2/blood , Chemokine CCL2/metabolism , Corpus Striatum/cytology , Corpus Striatum/immunology , Corpus Striatum/pathology , Disease Models, Animal , Drugs, Chinese Herbal/therapeutic use , Haloperidol/pharmacology , Haloperidol/therapeutic use , Humans , Interleukin-6/blood , Interleukin-6/metabolism , Male , Microglia/immunology , Microglia/metabolism , Nitriles/toxicity , Rats , Rats, Wistar , Tourette Syndrome/chemically induced , Tourette Syndrome/immunology , Tourette Syndrome/pathology , Tumor Necrosis Factor-alpha/blood , Tumor Necrosis Factor-alpha/metabolismABSTRACT
Camellia oil has become an important plant oil in China in recent years, but its effects on non-alcoholic fatty liver disease (NAFLD) have not been documented. In this study, the effects of camellia oil, soybean oil, and olive oil on NAFLD were evaluated by analyzing the fatty acid profiles of the plant oils, the serum lipids and lipoproteins of rats fed different oils, and by cytological and ultrastructural observation of the rats’ hepatocytes. Analysis of fatty acid profiles showed that the polyunsaturated fatty acid (PUFA) n-6/n-3 ratio was 33.33 in camellia oil, 12.50 in olive oil, and 7.69 in soybean oil. Analyses of serum lipids and lipoproteins of rats showed that the levels of total cholesterol and low-density lipoprotein cholesterol in a camellia oil-fed group (COFG) were lower than those in an olive oil-fed group (OOFG) and higher than those in a soybean oil-fed group (SOFG). However, only the difference in total cholesterol between the COFG and SOFG was statistically significant. Cytological observation showed that the degree of lipid droplet (LD) accumulation in the hepatocytes in the COFG was lower than that in the OOFG, but higher than that in the SOFG. Ultrastructural analysis revealed that the size and number of the LDs in the hepatocytes of rats fed each of the three types of oil were related to the degree of damage to organelles, including the positions of nuclei and the integrity of mitochondria and endoplasmic reticulum. The results revealed that the effect of camellia oil on NAFLD in rats was greater than that of soybean oil, but less than that of olive oil. Although the overall trend was that among the three oil diets, those with a lower n-6/n-3 ratio were associated with a lower risk of NAFLD, and the effect of camellia oil on NAFLD was not entirely related to the n-6/n-3 ratio and may have involved other factors. This provides new insights into the effect of oil diets on NAFLD.
ABSTRACT
Next Generation Sequencing (NGS) has dramatically improved the flexibility and outcomes of cancer research and clinical trials, providing highly sensitive and accurate high-throughput platforms for large-scale genomic testing. In contrast to whole-genome (WGS) or whole-exome sequencing (WES), targeted genomic sequencing (TS) focuses on a panel of genes or targets known to have strong associations with pathogenesis of disease and/or clinical relevance, offering greater sequencing depth with reduced costs and data burden. This allows targeted sequencing to identify low frequency variants in targeted regions with high confidence, thus suitable for profiling low-quality and fragmented clinical DNA samples. As a result, TS has been widely used in clinical research and trials for patient stratification and the development of targeted therapeutics. However, its transition to routine clinical use has been slow. Many technical and analytical obstacles still remain and need to be discussed and addressed before large-scale and cross-centre implementation. Gold-standard and state-of-the-art procedures and pipelines are urgently needed to accelerate this transition. In this review we first present how TS is conducted in cancer research, including various target enrichment platforms, the construction of target panels, and selected research and clinical studies utilising TS to profile clinical samples. We then present a generalised analytical workflow for TS data discussing important parameters and filters in detail, aiming to provide the best practices of TS usage and analyses.
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OBJECTIVE: To evaluate the therapeutic effect of auricular acupuncture combined with dydrogesterone for threatened abortion in early pregnancy complicated with subchorionic hematoma. METHODS: A total of 80 patients were randomized into an observation group and a control group, 40 cases in each one. In the control group, dydrogesterone was taken orally twice a day, 10 mg a time until 12-week into pregnancy. In the observation groupï¼auricular acupuncture was applied at penqiang (TF5), pizhixia (AT4), shen (CO10), xin(CO15), gan (CO12), jiaogan (AH6a) and neifenmi (CO18) on the basis of the control group, the auricular points on both sides were used alternatively. The auricular points were replaced every 3 days with 1 day break, totally 3 weeks (20 days) were required. Before treatment and after 10, 20 days of treatment, the percentage of helper T lymphocyte (Th) and inhibitory T lymphocyte (Ts), ratio of Th and Ts and serum level of CA125 were compared in the two groups. The areas of subchorionic hematoma and gestational sac were evaluated by B ultrasound. The therapeutic effect in the two groups were compared. RESULTS: The effective rate in the observation group was 80.0% (32/40), which was superior to 65.0% (26/40) in the control group (P<0.05). After 10, 20 days of treatment, the percentage of Th and ratio of Th and Ts were lower than before treatment, the percentage of Ts were increased in the two groups (P<0.01). After 20 days of treatment, the percentage of Th and ratio of Th and Ts in the observation group were lower than the control group (P<0.01), the percentage of Ts was higher than the control group (P<0.01). After 10, 20 days of treatment, the serum levels of CA125 were reduced compared before treatment in the two groups (P<0.01), and the serum levels of CA125 in the observation group were lower than the control group (P<0.01). After 10, 20 days of treatment, the ratio of subchorionic hematoma area and gestational sac area in the observation group was lower than the control group (P<0.01). CONCLUSION: Auricular acupuncture combined with dextroprogesterone can improve the effective rate of patients with threatened abortion in early pregnancy complicated with subchorionic hematoma, regulate immune factors, promote the hematoma absorption, and has a better synergistic effect with dextroprogesterone.
Subject(s)
Abortion, Threatened , Acupuncture, Ear , Dydrogesterone/therapeutic use , Abortion, Threatened/prevention & control , Acupuncture Points , Acupuncture, Ear/methods , Combined Modality Therapy , Female , Hematoma/complications , Humans , Immunologic Factors , PregnancyABSTRACT
Down syndrome (DS), trisomy 21, is marked by intellectual disability and a premature aging profile including degeneration of the basal forebrain cholinergic neuron (BFCN) projection system, similar to Alzheimer's disease (AD). Although data indicate that perinatal maternal choline supplementation (MCS) alters the structure and function of these neurons in the Ts65Dn mouse model of DS and AD (Ts), whether MCS affects the molecular profile of vulnerable BFCNs remains unknown. We investigated the genetic signature of BFCNs obtained from Ts and disomic (2N) offspring of Ts65Dn dams maintained on a MCS diet (Ts+, 2N+) or a choline normal diet (ND) from mating until weaning, then maintained on ND until 4.4-7.5 months of age. Brains were then collected and prepared for choline acetyltransferase (ChAT) immunohistochemistry and laser capture microdissection followed by RNA extraction and custom-designed microarray analysis. Findings revealed upregulation of select transcripts in classes of genes related to the cytoskeleton (Tubb4b), AD (Cav1), cell death (Bcl2), presynaptic (Syngr1), immediate early (Fosb, Arc), G protein signaling (Gabarap, Rgs10), and cholinergic neurotransmission (Chrnb3) in Ts compared to 2N mice, which were normalized with MCS. Moreover, significant downregulation was seen in select transcripts associated with the cytoskeleton (Dync1h1), intracellular signaling (Itpka, Gng3, and Mlst8), and cell death (Ccng1) in Ts compared to 2N mice that was normalized with MCS. This study provides insight into genotype-dependent differences and the effects of MCS at the molecular level within a key vulnerable cell type in DS and AD.
Subject(s)
Basal Forebrain/metabolism , Choline/administration & dosage , Cholinergic Neurons/metabolism , Dietary Supplements , Down Syndrome/genetics , Down Syndrome/metabolism , Animals , Basal Forebrain/drug effects , Cholinergic Neurons/drug effects , Disease Models, Animal , Down Syndrome/drug therapy , Female , Gene Expression , Male , Mice , Mice, Inbred C57BL , Mice, Transgenic , PregnancyABSTRACT
BACKGROUND: FOLFIRINOX chemotherapy displays significant survival improvements in patients with pancreatic cancer. However, toxicities have hampered enthusiasm for the use of FOLFIRINOX in full dose. In order to increase the tolerability, many researchers focused on the modification of FOLFIRINOX. On the other hand, hyperthermia (HT) has been considered as an effective ancillary treatment for cancer therapy. Up to now, there is no report evaluating combining deep regional hyperthermia (DRHT) with modified-FOLFIRINOX for pancreatic cancer patients. METHODS: In this study, we conducted a retrospective review of pancreatic cancer patients treated with the combination of new form modified-FOLFIRINOX and DRHT (BSD2000). Patients underwent chemotherapy that included low-dose irinotecan (70-130 mg/m2), oxaliplatin (65-70 mg/m2) on day 1 and 5-FU (2400 mg/m2 as a 46 h continuous infusion, no bolus) or capecitabine (CAP) (1000 mg/m2 twice daily on days 1-10) or tegafur, gimeracil and oteracil potassium (TS-1) (80-120 mg/d twice daily on days 1-10), 2-week schedule. Generally, DRHT treatment was performed weekly, 45 min for each time during chemotherapy. RESULTS: The patients receiving mFOLFIRINOX as the first line chemotherapy combining with DRHT, obtained an improvement in OS and PFS, 17 months (95% CI 1.97-32.03 months) and 4 months (95% CI 0-8.29 months) respectively. Overall, this combination regimen was safe; 17.6% patients suffered from grade 3/4 toxicities. CONCLUSIONS: In conclusion, we conducted a retrospective study combining mFOLFIRINOX and DRHT, which was well tolerated. The efficacy in the treatment of pancreatic cancer was encouraging, but further studies would be required to prove its merit, compared with conventional treatment.
Subject(s)
Fluorouracil/therapeutic use , Irinotecan/therapeutic use , Oxaliplatin/therapeutic use , Pancreatic Neoplasms/drug therapy , Pancreatic Neoplasms/therapy , Aged , China , Female , Fluorouracil/pharmacology , Humans , Hyperthermia, Induced , Irinotecan/pharmacology , Male , Middle Aged , Oxaliplatin/pharmacology , Pancreatic Neoplasms/pathology , Retrospective Studies , Treatment OutcomeABSTRACT
OBJECTIVE@#To evaluate the therapeutic effect of auricular acupuncture combined with dydrogesterone for threatened abortion in early pregnancy complicated with subchorionic hematoma.@*METHODS@#A total of 80 patients were randomized into an observation group and a control group, 40 cases in each one. In the control group, dydrogesterone was taken orally twice a day, 10 mg a time until 12-week into pregnancy. In the observation group,auricular acupuncture was applied at penqiang (TF), pizhixia (AT), shen (CO), xin(CO), gan (CO), jiaogan (AH) and neifenmi (CO) on the basis of the control group, the auricular points on both sides were used alternatively. The auricular points were replaced every 3 days with 1 day break, totally 3 weeks (20 days) were required. Before treatment and after 10, 20 days of treatment, the percentage of helper T lymphocyte (Th) and inhibitory T lymphocyte (Ts), ratio of Th and Ts and serum level of CA125 were compared in the two groups. The areas of subchorionic hematoma and gestational sac were evaluated by B ultrasound. The therapeutic effect in the two groups were compared.@*RESULTS@#The effective rate in the observation group was 80.0% (32/40), which was superior to 65.0% (26/40) in the control group (<0.05). After 10, 20 days of treatment, the percentage of Th and ratio of Th and Ts were lower than before treatment, the percentage of Ts were increased in the two groups (<0.01). After 20 days of treatment, the percentage of Th and ratio of Th and Ts in the observation group were lower than the control group (<0.01), the percentage of Ts was higher than the control group (<0.01). After 10, 20 days of treatment, the serum levels of CA125 were reduced compared before treatment in the two groups (<0.01), and the serum levels of CA125 in the observation group were lower than the control group (<0.01). After 10, 20 days of treatment, the ratio of subchorionic hematoma area and gestational sac area in the observation group was lower than the control group (<0.01).@*CONCLUSION@#Auricular acupuncture combined with dextroprogesterone can improve the effective rate of patients with threatened abortion in early pregnancy complicated with subchorionic hematoma, regulate immune factors, promote the hematoma absorption, and has a better synergistic effect with dextroprogesterone.
Subject(s)
Female , Humans , Pregnancy , Abortion, Threatened , Acupuncture Points , Acupuncture, Ear , Methods , Combined Modality Therapy , Dydrogesterone , Therapeutic Uses , Hematoma , Immunologic FactorsABSTRACT
Litchi (Litchi chinensis Sonn.) and longan (Dimocarpus longan Lour.) fruits have a succulent and white aril with a brown seed and are becoming popular worldwide. The two fruits have been used in traditional Chinese medicine as popular herbs in the treatment of neural pain, swelling, and cardiovascular disease. The pericarp and seed portions as the by-products of litchi and longan fruits are estimated to be approximately 30% of the dry weight of the whole fruit and are rich in bioactive constituents. In the recent years, many biological activities, such as tyrosinase inhibitory, antioxidant, anti-inflammatory, immunomodulatory, anti-glycated, and anti-cancer activities, as well as memory-increasing effects, have been reported for the litchi and longan pericarp and seed extracts, indicating a potentially significant contribution to human health. With the increasing production of litchi and longan fruits, enhanced utilization of the two fruit by-products for their inherent bioactive constituents in relation to pharmacological effects is urgently needed. This paper reviews the current advances in the extraction, processing, identification, and biological and pharmacological activities of constituents from litchi and longan by-products. Potential utilization of litchi and longan pericarps and seeds in relation to further research is also discussed.
ABSTRACT
BACKGROUND AND OBJECTIVES: Irreversible electroporation (IRE) is a non-thermal focal therapy that utilizes high voltage electric pulses to permanently rupture the cellular membrane and induce cell death. In this multi-center study, we evaluated the safety and efficacy of IRE in patients with locally advanced pancreatic cancer (LAPC). METHODS: From 2012 to 2015, we performed laparotomic and laparoscopic IRE in a total of 70 patients with stage III LAPC. Either gemcitabine-based or TS-1 (Tegafur, Gimeracil, and Oteracil) chemotherapy was applied for at least 3 months before the IRE. RESULTS: No IRE-related deaths occurred. A median follow-up of 28.1 months showed that six patients (8.6%) experienced local recurrence and 24 (34%) experienced distant progression. The overall median survival from the time of treatment was 22.6 months, and the progression-free survival (PFS) was 15.4 months. The overall survival in the patients who used gemcitabine-based reagents was 19.1 months and that of those who used TS-1 was 28.7 months. The PFS for these two groups were 13.2 months and 26.4 months; the difference is significant. CONCLUSIONS: Our study suggests that IRE is safe and effective for the control of LAPC. We surmise that the addition of IRE to a chemotherapy regimen may provide a survival advantage.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Catheter Ablation/methods , Electrochemotherapy/methods , Pancreatic Neoplasms/drug therapy , Pancreatic Neoplasms/surgery , Adenocarcinoma/drug therapy , Adenocarcinoma/surgery , Chemotherapy, Adjuvant , Deoxycytidine/administration & dosage , Deoxycytidine/analogs & derivatives , Disease-Free Survival , Drug Combinations , Fluorouracil/administration & dosage , Humans , Induction Chemotherapy , Laparotomy/methods , Oxonic Acid/administration & dosage , Pyridines/administration & dosage , Survival Rate , Tegafur/administration & dosage , GemcitabineABSTRACT
Individuals with Down syndrome (DS), a genetic condition due to triplication of Chromosome 21, are characterized by intellectual disability that worsens with age. Since impairment of neurogenesis and dendritic maturation are very likely key determinants of intellectual disability in DS, interventions targeted to these defects may translate into a behavioral benefit. While most of the neurogenesis enhancers tested so far in DS mouse models may pose some caveats due to possible side effects, substances naturally present in the human diet may be regarded as therapeutic tools with a high translational impact. Linoleic acid and oleic acid are major constituents of corn oil that positively affect neurogenesis and neuron maturation. Based on these premises, the goal of the current study was to establish whether treatment with corn oil improves hippocampal neurogenesis and hippocampus-dependent memory in the Ts65Dn model of DS. Four-month-old Ts65Dn and euploid mice were treated with saline or corn oil for 30 days. Evaluation of behavior at the end of treatment showed that Ts65Dn mice treated with corn oil underwent a large improvement in hippocampus-dependent learning and memory. Evaluation of neurogenesis and dendritogenesis showed that in treated Ts65Dn mice the number of new granule cells of the hippocampal dentate gyrus and their dendritic pattern became similar to those of euploid mice. In addition, treated Ts65Dn mice underwent an increase in body and brain weight. This study shows for the first time that fatty acids have a positive impact on the brain of the Ts65Dn mouse model of DS. These results suggest that a diet that is rich in fatty acids may exert beneficial effects on cognitive performance in individuals with DS without causing adverse effects.
Subject(s)
Cognition , Corn Oil/administration & dosage , Down Syndrome/therapy , Neurogenesis , Animals , Cells, Cultured , Disease Models, Animal , Down Syndrome/pathology , Down Syndrome/physiopathology , Down Syndrome/psychology , Hippocampus/pathology , Hippocampus/physiopathology , Male , Memory , Mice, Inbred C3H , Mice, Inbred C57BL , Mice, Transgenic , Neurons/pathology , Neurons/physiologyABSTRACT
PURPOSE OF REVIEW: Tourette syndrome (TS) is a neuropsychiatric condition defined by both motor and phonic tics over a period of at least 1 year with the onset before 18 years of age. The purpose of this article is to review the use of complementary alternative medicine (CAM) in children and adults with Tourette syndrome with emphasis on recent research. RECENT FINDINGS: Most patients do not tell their physician about the use of CAM unless if specifically asked. Of the studies reviewed, description of the treatment and the frequency of use were most often reported. Few studies examine the role or effectiveness of CAM in the treatment of TS specifically. SUMMARY: Practitioners should be aware of current research regarding various CAM modalities used for TS patients, including efficacy, potential adverse effects, and interactions with medications. Robust data about the use of CAM, efficacy, and potential side effects is lacking and requires further research to clarify optimal use.