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1.
Int J Mol Sci ; 25(7)2024 Mar 25.
Article in English | MEDLINE | ID: mdl-38612475

ABSTRACT

MAPKKs, as one of the main members of the mitogen-activated protein kinase (MAPK) cascade pathway, are located in the middle of the cascade and are involved in many physiological processes of plant growth and development, as well as stress tolerance. Previous studies have found that StMAPKK5 is responsive to drought and salt stress. To further investigate the function and regulatory mechanism of StMAPKK5 in potato stress response, potato variety 'Atlantic' was subjected to drought and NaCl treatments, and the expression of the StMAPKK5 gene was detected by qRT-PCR. StMAPKK5 overexpression and RNA interference-mediated StMAPKK5 knockdown potato plants were constructed. The relative water content, superoxide dismutase (SOD), catalase (CAT), and peroxidase (POD) activities, as well as proline (Pro) and malondialdehyde (MDA) contents of plant leaves, were also assayed under drought and NaCl stress. The StMAPKK5 interacting proteins were identified and validated by yeast two-hybrid (Y2H) and bimolecular fluorescence complementation (BiFC). The results showed that the expression of StMAPKK5 was significantly up-regulated under drought and NaCl stress conditions. The StMAPKK5 protein was localized in the nucleus, cytoplasm, and cell membrane. The expression of StMAPKK5 affected the relative water content, the enzymatic activities of SOD, CAT, and POD, and the proline and MDA contents of potatoes under drought and salt stress conditions. These results suggest that StMAPKK5 plays a significant role in regulating drought and salt tolerance in potato crop. Yeast two-hybrid (Y2H) screening identified four interacting proteins: StMYB19, StZFP8, StPUB-like, and StSKIP19. BiFC confirmed the authenticity of the interactions. These findings suggest that StMAPKK5 is crucial for potato growth, development, and response to adversity.


Subject(s)
Solanum tuberosum , Solanum tuberosum/genetics , Droughts , Saccharomyces cerevisiae , Sodium Chloride/pharmacology , Salt Stress , Proline , Superoxide Dismutase , Water
2.
Zhongguo Zhong Yao Za Zhi ; 49(5): 1217-1224, 2024 Mar.
Article in Chinese | MEDLINE | ID: mdl-38621968

ABSTRACT

To investigate the quality differences between the seeds and husks of Amomum villosum and explore the rationality of using the seeds without husks, this study determined the content of protocatechuic acid, vanillic acid, epicatechin, quercitrin, volatile oil, water extract, and ethanol extract. The 2,2-diphenyl-1-picrylhydrazyl(DPPH), 2,2-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid)(ABTS), and hydroxyl radical scavenging activities were determined to evaluate the antioxidant activities of seeds and husks. The quality differences between the seeds and husks were assessed through orthogonal partial least squares-discriminant analysis(OPLS-DA) and analytic hierarchy process(AHP) combined with the entropy weight method(EWM). Significant differences(P<0.05) were observed in all 10 indicators between the seeds and husks. The levels of epicatechin, quercetin, and volatile oil were higher in the seeds, whereas those of protocatechuic acid, vanillic acid, water extract, and ethanol extract were higher in the husks. The seeds showed stronger scavenging ability against DPPH and ABTS radicals, while the husks showed a stronger scavenging effect on hydroxyl radicals. OPLS-DA significantly discriminated between the seeds and husks. Furthermore, volatile oil, water extract, DPPH radical scavenging rate, quercitrin, ABTS radical scavenging rate, hydroxyl radical scavenging rate, and vanillic acid were selected as the main differential indicators by variable importance in projection(VIP). Comprehensive scores calculated by AHP combined with EWM indicated that the seeds were superior to husks in terms of overall quality. However, there are still some dominant components and a certain antioxidant effect in the husks. Therefore, it is suggested to using Amomi Fructus with a certain amount of husks or utilizing the husks for other purposes.


Subject(s)
Amomum , Benzothiazoles , Catechin , Hydroxybenzoates , Oils, Volatile , Sulfonic Acids , Hydroxyl Radical , Vanillic Acid , Antioxidants/chemistry , Water , Ethanol , Oils, Volatile/chemistry
3.
BMC Plant Biol ; 24(1): 170, 2024 Mar 05.
Article in English | MEDLINE | ID: mdl-38443797

ABSTRACT

BACKGROUND: Panax notoginseng (Burk) F. H. Chen is one of the most famous Chinese traditional medicinal plants. The taproot is the main organ producing triterpenoid saponins, and its development is directly linked to the quality and yield of the harvested P. notoginseng. However, the mechanisms underlying the dynamic metabolic changes occurring during taproot development of P. notoginseng are unknown. RESULTS: We carried out metabolomic and transcriptomic analyses to investigate metabolites and gene expression during the development of P. notoginseng taproots. The differentially accumulated metabolites included amino acids and derivatives, nucleotides and derivatives, and lipids in 1-year-old taproots, flavonoids and terpenoids in 2- and 3-year-old taproots, and phenolic acids in 3-year-old taproots. The differentially expressed genes (DEGs) are related to phenylpropanoid biosynthesis, metabolic pathway and biosynthesis of secondary metabolites at all three developmental stages. Integrative analysis revealed that the phenylpropanoid biosynthesis pathway was involved in not only the development of but also metabolic changes in P. notoginseng taproots. Moreover, significant accumulation of triterpenoid saponins in 2- and 3-year-old taproots was highly correlated with the up-regulated expression of cytochrome P450s and uridine diphosphate-dependent glycosyltransferases genes. Additionally, a gene encoding RNase-like major storage protein was identified to play a dual role in the development of P. notoginseng taproots and their triterpenoid saponins synthesis. CONCLUSIONS: These results elucidate the molecular mechanism underlying the accumulation of and change relationship between primary and secondary metabolites in P. notoginseng taproots, and provide a basis for the quality control and genetic improvement of P. notoginseng.


Subject(s)
Panax notoginseng , Saponins , Triterpenes , Panax notoginseng/genetics , Metabolome , Gene Expression Profiling
4.
Biol Trace Elem Res ; 202(3): 955-964, 2024 Mar.
Article in English | MEDLINE | ID: mdl-37462848

ABSTRACT

Copper is an essential trace element for the human body. The epidemiological evidence for the association of dietary intake of copper with the risk of Parkinson's disease (PD) is limited. We conducted an evaluation of the cross-sectional data gathered from the National Health and Nutrition Examination Surveys spanning from 2007 to 2018, which comprised a total of 17,948 participants. To discern the distinct characteristics of the participants, we performed a univariate analysis and utilized a 1:2 ratio propensity score matching method to minimize the effects of selection bias. We employed weighted univariate as well as three multivariate logistic regression models both prior to and following matching, with the aim of examining the association between dietary copper intake and PD risk. Finally, we used the restricted cubic spline (RCS) methodology in order to investigate possible non-linear relationships. Furthermore, subgroup analysis was undertaken to elicit further understanding concerning the association between copper intake and PD. A negative correlation resulted between dietary copper intake and PD risk in both univariate and multivariate logistic regression models, prior to and following matching. Our findings demonstrate that there is a nonlinear, dose-dependent relationship between copper intake and PD, according to our RCS analysis. In subgroup analysis, copper intake was identified as an important protective factor for individuals who were non-Hispanic White, unmarried, and had completed higher education. Dietary copper intake was associated with the risk of PD. Supplementation of dietary copper may have potentially beneficial effects.


Subject(s)
Copper , Parkinson Disease , Humans , Cross-Sectional Studies , Diet , Parkinson Disease/epidemiology , Parkinson Disease/etiology , Nutritional Status , Nutrition Surveys
5.
J Colloid Interface Sci ; 657: 619-631, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38071811

ABSTRACT

The reactive oxygen species (ROS) produced through the Fenton reaction, induces lipid peroxide (LPO), causing cellular structural damage and ultimately triggering ferroptosis. However, the generation of ROS in the tumor microenvironment (TME) is limited by the catalytic efficiency of the Fenton reaction. Herein, a novel hollow mesoporous silica nanoparticle (HMSN) combined with multi-metal sulfide-doped mesoporous silica nanocatalyzers (NCs) was developed, namely MxSy-HMSN NCs (M represents Cu Mn and Fe, S denotes sulfur). The MxSy-HMSN can dramatically enhanced the ferroptosis by: (1) facilitating the conversion of H2O2 to ·OH through Fenton or Fenton-like reactions through co-catalysis; (2) weakening ROS scavenging systems by depleting the over expressed glutathione (GSH) in TME; (3) providing exceptional photothermal therapy to augment ferroptosis. The MxSy-HMSN can also act as smart cargos for anticancer drug-doxorubicin (DOX). The release of DOX is responsive to GSH/pH/Near-infrared Light (NIR) irradiation at the tumor lesion, significantly improving therapeutic outcomes while minimizing side effects. Additionally, the MxSy-HMSN has demonstrated excellent magnetic resonance imaging (MRI) potential. This smart MxSy-HMSN offer a synergetic approach combining ferroptosis with chemo-photothermal therapy and magnetic resonance imaging (MRI) diagnose, which could be an informative guideline for the design of future NCs.


Subject(s)
Antineoplastic Agents , Ferroptosis , Hereditary Sensory and Motor Neuropathy , Nanoparticles , Neoplasms , Humans , Photothermal Therapy , Phototherapy/methods , Precision Medicine , Reactive Oxygen Species , Hydrogen Peroxide , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use , Doxorubicin/chemistry , Neoplasms/drug therapy , Neoplasms/pathology , Nanoparticles/chemistry , Silicon Dioxide/chemistry , Hereditary Sensory and Motor Neuropathy/drug therapy , Cell Line, Tumor , Tumor Microenvironment
6.
J Agric Food Chem ; 71(49): 19165-19188, 2023 Dec 13.
Article in English | MEDLINE | ID: mdl-38019642

ABSTRACT

Rhizosphere microbial colonization of the tea plant provides many beneficial functions for the host, But the factors that influence the composition of these rhizosphere microbes and their functions are still unknown. In order to explore the interaction between tea plants and rhizosphere microorganisms, we summarized the current studies. First, the review integrated the known rhizosphere microbial communities of tea tree, including bacteria, fungi, and arbuscular mycorrhizal fungi. Then, various factors affecting tea rhizosphere microorganisms were studied, including: endogenous factors, environmental factors, and agronomic practices. Finally, the functions of rhizosphere microorganisms were analyzed, including (a) promoting the growth and quality of tea trees, (b) alleviating biotic and abiotic stresses, and (c) improving soil fertility. Finally, we highlight the gaps in knowledge of tea rhizosphere microorganisms and the future direction of development. In summary, understanding rhizosphere microbial interactions with tea plants is key to promoting the growth, development, and sustainable productivity of tea plants.


Subject(s)
Camellia sinensis , Microbiota , Mycorrhizae , Rhizosphere , Soil , Trees , Tea , Soil Microbiology , Plant Roots/microbiology
7.
Medicine (Baltimore) ; 102(40): e34943, 2023 Oct 06.
Article in English | MEDLINE | ID: mdl-37800756

ABSTRACT

BACKGROUND: Although increasing evidence has revealed the efficacy of acupuncture in obesity/overweight, actual improvement in metabolism in children and adolescents is unclear. Therefore, we conducted a meta-analysis to evaluate this correlation. METHODS: A comprehensive search was conducted using multiple databases, including Medline, Cochrane, Embase, Web of Science, Chinese Biomedical Literature Database, China National Knowledge Infrastructure, Chinese Scientific Journal Database, and Wan-fang Data, to identify relevant randomized controlled trials published before February 1, 2023. General information and data for the descriptive and quantitative analyses were extracted. RESULTS: Fifteen randomized controlled trials of 1288 obese/overweight children and teenagers were included. All the trials were conducted in China and South Korea. Regarding quality assessment, no other significant risk of bias was found. The acupuncture groups were more likely to have improved metabolic indicators of obesity/overweight than the control groups, in terms of body mass index (standardized mean difference [SMD] = -0.45, 95% confidence interval [CI]: -0.69 to -0.21, I2 = 71.4%), body weight (SMD = -0.48, 95% CI: -0.92 to -0.05, I2 = 84.9%), and serum leptin (SMD = -0.34, 95% CI: -0.58 to -0.10, I2 = 91.8%). The subgroup analysis showed that for body mass index, the results were consistent regardless of the intervention duration, body acupuncture or auricular acupuncture combined with other interventions. CONCLUSION: Our results suggest that acupuncture is effective in improving metabolic outcomes of obese/overweight children and adolescents. Owing to the limited number of trials included in this study, the results should be interpreted with caution.


Subject(s)
Acupuncture Therapy , Overweight , Adolescent , Humans , Child , Overweight/therapy , Obesity/therapy , Acupuncture Therapy/methods , Body Mass Index , China
8.
BMC Geriatr ; 23(1): 695, 2023 10 26.
Article in English | MEDLINE | ID: mdl-37880590

ABSTRACT

BACKGROUND: Individuals with mild cognitive impairment are at high risk of developing dementia. Dance therapy has promising applications in delaying cognitive decline. However, the effectiveness of dance therapy for older adults with mild cognitive impairment is unclear. The objective of this review was to evaluate the effectiveness of dance therapy on global cognitive function, specific cognitive subdomains, quality of life, and mental health in older adults with mild cognitive impairment to enrich health management strategies for dementia. METHODS: Electronic databases and grey literature were searched from inception up to September 23, 2023. The language was limited to English and Chinese. Relevant studies were screened and assessed for risk of bias. A meta-analysis and subgroup analyses stratified by measurement instrument, dance type, intervention duration, and frequency were conducted using the STATA 16.0 software. This review was conducted in accordance with the PRISMA guidelines. RESULTS: Ten studies involving 984 participants aged 55 years and over who met the eligibility criteria were included. Dance therapy significantly improved global cognitive function, memory, executive function, attention, language, and mental health (i.e., depression and neuropsychiatric symptoms). However, the effects of dance therapy on processing speed, visuospatial ability, and quality of life in older adults with mild cognitive impairment remain inconclusive. Moreover, dance interventions of longer duration (> 3 months) improved global cognition more than shorter interventions. CONCLUSION: This review reported that dance therapy was effective in improving global cognitive function, memory, executive function, attention, language, and mental health (i.e., depression and neuropsychiatric symptoms). Hence, it may be an effective non-pharmacological complementary treatment for older adults with mild cognitive impairment.


Subject(s)
Cognitive Dysfunction , Dance Therapy , Dementia , Humans , Aged , Mental Health , Quality of Life , Cognitive Dysfunction/therapy , Cognition
9.
Front Neurosci ; 17: 1251470, 2023.
Article in English | MEDLINE | ID: mdl-37732301

ABSTRACT

Irritable Bowel Syndrome (IBS) is a complex functional gastrointestinal disorder primarily characterized by chronic abdominal pain, bloating, and altered bowel habits. Chronic abdominal pain caused by visceral Hypersensitivity (VH) is the main reason why patients with IBS seek medication. Significant research effort has been devoted to the efficacy of acupuncture as a non-drug alternative therapy for visceral-hyperalgesia-induced IBS. Herein, we examined the central and peripheral analgesic mechanisms of acupuncture in IBS treatment. Acupuncture can improve inflammation and relieve pain by reducing 5-hydroxytryptamine and 5-HT3A receptor expression and increasing 5-HT4 receptor expression in peripheral intestinal sensory endings. Moreover, acupuncture can also activate the transient receptor potential vanillin 1 channel, block the activity of intestinal glial cells, and reduce the secretion of local pain-related neurotransmitters, thereby weakening peripheral sensitization. Moreover, by inhibiting the activation of N-methyl-D-aspartate receptor ion channels in the dorsal horn of the spinal cord and anterior cingulate cortex or releasing opioids, acupuncture can block excessive stimulation of abnormal pain signals in the brain and spinal cord. It can also stimulate glial cells (through the P2X7 and prokinetic protein pathways) to block VH pain perception and cognition. Furthermore, acupuncture can regulate the emotional components of IBS by targeting hypothalamic-pituitary-adrenal axis-related hormones and neurotransmitters via relevant brain nuclei, hence improving the IBS-induced VH response. These findings provide a scientific basis for acupuncture as an effective clinical adjuvant therapy for IBS pain.

10.
Heliyon ; 9(7): e18224, 2023 Jul.
Article in English | MEDLINE | ID: mdl-37539255

ABSTRACT

Background: Folic acid and zinc supplements have been used to treat male infertility, but their efficacy is still debated. Objective: To systematically evaluate the effects of folic acid and folic acid plus zinc supplements on sperm characteristics and pregnancy outcomes of infertile men. Methods: An online systematic search was performed using PubMed, Cochrane Library, and EMBASE databases from inception to August 1, 2022. The goal was to identify randomized controlled trials (RCTs) that used folic acid or folic acid plus zinc to improve sperm characteristics of infertile men. Data were extracted by two investigators who independently screened the literature and assessed for quality according to the criteria. The meta-analysis was performed using RevMan 5.4 software. Results: A total of 8 RCT studies involving 2168 patients were included. The results showed that compared with the controls, folic acid significantly increased sperm motility (MD, 3.63; 95% CI, -1.22 to 6.05; P = 0.003), but did not affect the sperm concentration (MD, 2.53; 95% CI, -1.68 to 6.73; P = 0.24) and sperm morphology (MD, -0.02; 95% CI, -0.29 to 0.24; P = 0.86) in infertile men. Folic acid plus zinc did not affect sperm concentration (MD, 1.87; 95% CI, -1.39 to 5.13; P = 0.26), motility (MD, 1.67; 95% CI, -1.29 to 4.63; P = 0.27), and morphology (MD, -0.05; 95% CI, -0.27 to 0.18; P = 0.69) in infertile men. Secondary results showed that compared with a placebo, folic acid alone had a higher rate of pregnancy in transferred embryos (35.6% vs. 20.4%, P = 0.082), but the difference was not significant. Folic acid plus zinc did not affect pregnancy outcomes. Conclusions: Based on the meta-analysis, no significant improvements in sperm characteristics with folic acid plus zinc supplements were seen. However, folic acid alone has demonstrated the potential to improve sperm motility and in vitro fertilization-intracytoplasmic sperm injection (IVF-ICSI) outcomes. This indicates that folic acid supplements alone may be a viable treatment option for male infertility.

11.
Microb Ecol ; 86(4): 2541-2551, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37401933

ABSTRACT

Long-term fertilization affects soil organic C accumulation. A growing body of research has revealed critical roles of bacteria in soil organic C accumulation, particularly through mineral-associated organic C (MAOC) formation. Protists are essential components of soil microbiome, but the relationships between MAOC formation and protists under long-term fertilization remain unclear. Here, we used cropland soil from a long-term fertilization field trial and conducted two microcosm experiments with 13C-glucose addition to investigate the effects of N and P fertilizations on MAOC formation and the relationships with protists. The results showed that long-term fertilization (especially P fertilization) significantly (P < 0.05) increased 13C-MAOC content. Compared with P-deficient treatment, P replenishment enriched the number of protists (mainly Amoebozoa and Cercozoa) and bacteria (mainly Acidobacteriota, Bacteroidota, and Gammaproteobacteria), and significantly (P < 0.001) promoted the abundances of bacterial functional genes controlling C, N, P, and S metabolisms. The community composition of phagotrophic protists prominently (P < 0.001) correlated with the bacterial community composition, bacterial functional gene abundance, and 13C-MAOC content. Co-occurrence networks of phagotrophic protists and bacteria were more connected in soil with the N inoculum added than in soil with the NP inoculum added. P replenishment strengthened bacterial 13C assimilation (i.e., 13C-phospholipid fatty acid content), which negatively (P < 0.05) correlated with the number and relative abundance of phagotrophic Cercozoa. Together, these results suggested that P fertilization boosts MAOC formation associated with phagotrophic protists. Our study paves the way for future research to harness the potential of protists to promote belowground C accrual in agroecosystems.


Subject(s)
Phosphorus , Soil , Phosphorus/metabolism , Carbon/metabolism , Soil Microbiology , Minerals/metabolism , Bacteria/genetics , Bacteria/metabolism , Fertilizers/analysis , Fertilization
12.
Zhongguo Zhong Yao Za Zhi ; 48(11): 2856-2867, 2023 Jun.
Article in Chinese | MEDLINE | ID: mdl-37381948

ABSTRACT

Hyperplasia of mammary glands is a benign breast disease with disordered breast structure. Nowadays, the incidence rate of breast hyperplasia in women is increasing year by year, and the etiology is related to the imbalance of estrogen and progesterone in the body. The symptoms include breast pain, breast nodules, or nipple discharge, which can develop into breast cancer in the context of psychological pressure. Therefore, it is timely and effectively necessary for people to treat the symptoms. At present, traditional Chinese medicine(TCM) often treats breast hyperplasia by oral drug, external application, acupuncture, moxibustion, and massage, while western medicine often uses hormone therapy or surgery. TCM can regulate hormone levels to treat breast hyperplasia. Acupuncture, moxibustion, and other methods can stimulate acupoints to reduce breast lumps. However, since TCM is easy to produce hepatorenal toxicity after long-term use and simple external treatment is slow to take effect, rapid and effective treatment is difficult to be achieved. Although western medicine can inhibit the disease, it is easy to produce toxic and side effects if taken for a long time. In addition, surgery can only remove the focus and the recurrence rate is high. Some studies have found that the combination of oral and external use of TCM compounds has a significant effect, with mild toxic and side effects, few adverse reactions, and a low recurrence rate. Based on the relevant literature in recent years, this article reviewed the combination of oral and external treatment of TCM in the treatment of hyperplasia of mammary glands, discussed the effectiveness, clinical evaluation indexes, and mechanism, and pointed out the existing shortcomings to explore a comprehensive therapy worthy of clinical application.


Subject(s)
Acupuncture Therapy , Breast Neoplasms , Drug-Related Side Effects and Adverse Reactions , Mammary Glands, Human , Female , Humans , Medicine, Chinese Traditional , Hyperplasia , Estrogens
13.
Zhongguo Zhong Yao Za Zhi ; 48(12): 3224-3234, 2023 Jun.
Article in Chinese | MEDLINE | ID: mdl-37382006

ABSTRACT

This study aims to investigate the efficacy and possible mechanism of Liuwei Dihuang Pills in the treatment of diminished ovarian reserve(DOR) by using proteomic techniques. Firstly, cyclophosphamide(60 mg·kg~(-1)) combined with busulfan(6 mg·kg~(-1)) was injected intraperitoneally to establish the mouse model of DOR. After drug injection, the mice were continuously observed and the success of modeling was evaluated by the disturbance of the estrous cycle. After successful modeling, the mice were administrated with the suspension of Liuwei Dihuang Pills by gavage for 28 days. At the end of the gavage, four female mice were selected and caged together with males at a ratio of 2∶1 for the determination of the pregnancy rate. Blood and ovary samples were collected from the remaining mice on the next day after the end of gavage. Hematoxylin-eosin(HE) staining and transmission electron microscopy(TEM) were then employed to observe the morphological and ultrastructural changes in the ovaries. The serum levels of hormones and oxidation indicators were measured by enzyme-linked immunosorbent assay. Quantitative proteomics techniques were used to compare the ovarian protein expression before and after modeling and before and after the intervention with Liuwei Dihuang Pills. The results showed that Liuwei Dihuang Pills regulated the estrous cycle of DOR mice, elevated the serum levels of hormones and anti-oxidation indicators, promoted follicle development, protected the mitochondrial morphology of ovarian granulosa cells, and increased the litter size and survival of DOR mice. Furthermore, Liuwei Dihuang Pills negatively regulated the expression of 12 differentially expressed proteins associated with DOR, which were mainly involved in lipid catabolism, inflammatory response, immune regulation, and coenzyme biosynthesis. These differentially expressed proteins were significantly enriched in sphingolipid metabolism, arachidonic acid metabolism, ribosomes, ferroptosis, and cGMP-PKG signaling pathway. In summary, the occurrence of DOR and the treatment of DOR with Liuwei Dihuang Pills are associated with multiple biological pathways, mainly including oxidative stress response, inflammatory response, and immune regulation. "Mitochondria-oxidative stress-apoptosis" is the key to the treatment of DOR by Liuwei Dihuang Pills. YY1 and CYP4F3 may be the key upstream targets that trigger mitochondrial dysfunction and ROS accumulation, and the metabolism of arachidonic acid is the main signaling pathway of drug action.


Subject(s)
Ovarian Reserve , Female , Male , Pregnancy , Animals , Mice , Arachidonic Acid , Proteomics , Ovary , Lipid Metabolism
14.
Phytomedicine ; 117: 154912, 2023 Aug.
Article in English | MEDLINE | ID: mdl-37295023

ABSTRACT

BACKGROUND: Therapeutic approaches based on glycolysis and energy metabolism of tumor cells are new promising strategies for the treatment of cancer. Currently, researches on the inhibition of pyruvate kinase M2, a key rate limiting enzyme in glycolysis, have been corroborated as an effective cancer therapy. Alkannin is a potent pyruvate kinase M2 inhibitor. However, its non-selective cytotoxicity has affected its subsequent clinical application. Thus, it needs to be structurally modified to develop novel derivatives with high selectivity. PURPOSE: Our study aimed to ameliorate the toxicity of alkannin through structural modification and elucidate the mechanism of the superior derivative 23 in lung cancer therapy. METHODS: On the basis of the principle of collocation, different amino acids and oxygen-containing heterocycles were introduced into the hydroxyl group of the alkannin side chain. We examined the cell viability of all derivatives on three tumor cells (HepG2, A549 and HCT116) and two normal cells (L02 and MDCK) by MTT assay. Besides, the effect of derivative 23 on the morphology of A549 cells as observed by Giemsa and DAPI staining, respectively. Flow cytometry was performed to assess the effects of derivative 23 on apoptosis and cell cycle arrest. To further assess the effect of derivative 23 on the Pyruvate kinase M2 in glycolysis, an enzyme activity assay and western blot assay were performed. Finally, in vivo the antitumor activity and safety of the derivative 23 were evaluated by using Lewis mouse lung cancer xenograft model. RESULTS: Twenty-three novel alkannin derivatives were designed and synthesized to improve the cytotoxicity selectivity. Among these derivatives, derivative 23 showed the highest cytotoxicity selectivity between cancer and normal cells. The anti-proliferative activity of derivative 23 on A549 cells (IC50 = 1.67 ± 0.34 µM) was 10-fold higher than L02 cells (IC50 = 16.77 ± 1.44 µM) and 5-fold higher than MDCK cells (IC50 = 9.23 ± 0.29 µM) respectively. Subsequently, fluorescent staining and flow cytometric analysis showed that derivative 23 was able to induce apoptosis of A549 cells and arrest the cell cycle in the G0/G1 phase. In addition, the mechanistic studies suggested derivative 23 was an inhibitor of pyruvate kinase; it could regulate glycolysis by inhibiting the activation of the phosphorylation of PKM2/STAT3 signaling pathway. Furthermore, studies in vivo demonstrated derivative 23 significantly inhibited the growth of xenograft tumor. CONCLUSION: In this study, alkannin selectivity is reported to be significantly improved following structural modification, and derivative 23 is first shown to be able to inhibit lung cancer growth via the PKM2/STAT3 phosphorylation signaling pathway in vitro, indicating the potential value of derivative 23 in treating lung cancer.


Subject(s)
Antineoplastic Agents , Lung Neoplasms , Naphthoquinones , Humans , Mice , Animals , Pyruvate Kinase/metabolism , Cell Line, Tumor , Naphthoquinones/pharmacology , Lung Neoplasms/drug therapy , Lung Neoplasms/pathology , Apoptosis , Cell Proliferation , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry
15.
World J Gastroenterol ; 29(14): 2134-2152, 2023 Apr 14.
Article in English | MEDLINE | ID: mdl-37122599

ABSTRACT

BACKGROUND: New drugs are urgently needed for the treatment of liver cancer, a feat that could be feasibly accomplished by finding new therapeutic purposes for marketed drugs to save time and costs. As a new class of national anti-infective drugs, carrimycin (CAM) has strong activity against gram-positive bacteria and no cross resistance with similar drugs. Studies have shown that the components of CAM have anticancer effects. AIM: To obtain a deeper understanding of CAM, its distribution, metabolism and anti-inflammatory effects were assessed in the organs of mice, and its mechanism of action against liver cancer was predicted by a network pharmacology method. METHODS: In this paper, the content of isovaleryl spiramycin III was used as an index to assess the distribution and metabolism of CAM and its effect on inflammatory factors in various mouse tissues and organs. Reverse molecular docking technology was utilized to determine the target of CAM, identify each target protein based on disease type, and establish a target protein-disease type network to ascertain the effect of CAM in liver cancer. Then, the key action targets of CAM in liver cancer were screened by a network pharmacology method, and the core targets were verified by molecular docking and visual analyses. RESULTS: The maximum CAM concentration was reached in the liver, kidney, lung and spleen 2.5 h after intragastric administration. In the intestine, the maximum drug concentration was reached 0.5 h after administration. In addition, CAM significantly reduced the interleukin-4 (IL-4) levels in the lung and kidney and especially the liver and spleen; moreover, CAM significantly reduced the IL-1ß levels in the spleen, liver, and kidney and particularly the small intestine and lung. CAM is predicted to regulate related pathways by acting on many targets, such as albumin, estrogen receptor 1, epidermal growth factor receptor and caspase 3, to treat cancer, inflammation and other diseases. CONCLUSION: We determined that CAM inhibited inflammation. We also predicted the complex multitargeted effects of CAM that involve multiple pathways and the diversity of these effects in the treatment of liver cancer, which provides a basis and direction for further clinical research.


Subject(s)
Drugs, Chinese Herbal , Liver Neoplasms , Animals , Mice , Molecular Docking Simulation , Liver Neoplasms/drug therapy , Inflammation/drug therapy , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/therapeutic use
16.
Bioresour Technol ; 380: 129095, 2023 Jul.
Article in English | MEDLINE | ID: mdl-37100303

ABSTRACT

The effects of the co-addition of fungal agents and biochar on physicochemical properties, odor emissions, microbial community structure, and metabolic functions were investigated during the in-situ treatment of food waste. The combined addition of fungal agents and biochar decreased cumulative NH3, H2S, and VOCs emissions by 69.37%, 67.50%, and 52.02%, respectively. The predominant phyla throughout the process were Firmicutes, Actinobacteria, Cyanobacteria, and Proteobacteria. Combined treatment significantly impacted the conversion and release of nitrogen from the perspective of the variation of nitrogen content between different forms. FAPROTAX analysis revealed that the combined application of fungal agents and biochar could effectively inhibit nitrite ammonification and reduce the emission of odorous gases. This work aims to clarify the combined effect of fungal agents and biochar on odor emission and provide a theoretical basis for developing an environmentally friendly in-situ efficient biological deodorization (IEBD) technology.


Subject(s)
Microbiota , Refuse Disposal , Soil/chemistry , Odorants , Food , Nitrogen/analysis , Charcoal/pharmacology
17.
Zhongguo Zhong Yao Za Zhi ; 48(1): 39-44, 2023 Jan.
Article in Chinese | MEDLINE | ID: mdl-36725256

ABSTRACT

Wilt disease is a major disease of cultivated Salvia miltiorrhiza, which is caused by Fusarium oxysporum. Since the infection process of F. oxysporum in plants is affected by environment factors, this study was conducted to reveal the relationship between disease severity and concentration of the pathogen in plants in the infection process of F. oxysporum in seedlings of S. miltiorrhiza by pot experiments and to reveal the effects of temperature and humidity on the infection process. The results showed that, after inoculation of S. miltiorrhiza seedlings with F. oxysporum, the pathogen in different parts was detected at different time, and it was first detected in substrates. With the continuous propagation of the pathogen(4-5 d), it gradually infected the roots and stems of the seedlings, and the plants had yellowing leaves and withering. The number of the pathogen reached the maximum in each part after 7-8 d, and then gradually decreased in the later stage of the disease. The concentration of the pathogen in substrates, roots and stems of S. miltiorrhiza showed a trend of decreasing after increasing with the aggravation of the disease and reached the maximum in the samples of moderate morbidity, while the concentration in the samples of severe morbidity decreased. In addition, the infection of F. oxysporum in seedlings of S. miltiorrhiza was affected by temperature and humidity. The suitable temperature was 25-30 ℃ and the suitable humidity was 80%-90%. This study could provide guidance for the experiments on pathogenicity of F. oxysporum, screening of biocontrol bacteria and controlling of wilt.


Subject(s)
Fusarium , Salvia miltiorrhiza , Seedlings/microbiology , Temperature , Humidity
18.
Sci Total Environ ; 854: 158583, 2023 Jan 01.
Article in English | MEDLINE | ID: mdl-36084774

ABSTRACT

Arsenic can be specifically enriched by rice, and the health hazards caused by high arsenic rice are gradually attracting attention. This study aimed to explore the potential of microbial detoxification via gut microbiome in the treatment of sub-chronic arsenic poisoning. We first exposed mice to high-dose arsenic feed (30 mg/kg, rice arsenic composition) for 60 days to promote arsenic-induced microbes in situ in the gastrointestinal tract, then transplanted their fecal microbiota (FMT) into another batch of healthy recipient mice, and dynamically monitored the microbial colonization by 16S rRNA sequencing and ITS sequencing. The results showed that in situ arsenic-induced fecal microbiome can stably colonized and interact with indigenous microbes in the recipient mice in two weeks, and established a more stable network of gut microbiome. Then, the recipient mice continued to receive high-dose arsenic exposure for 52 days. After above sub-chronic arsenic exposure, compared with the non-FMT group, fecal arsenic excretion, liver and plasma arsenic accumulation were significantly lower (P < 0.05), and that in kidney, hair, and thighbone present no significant differences. Metabolomics of feces- plasma-brain axis were also disturbed, some up-regulated metabolites in feces, plasma, and cerebral cortex may play positive roles for the host. Therefore, microbial detoxification has potential in the treatment of sub-chronic arsenic poisoning. However, gut flora is an extremely complex community with different microorganisms have different arsenic metabolizing abilities, and various microbial metabolites. Coupled with the matrix effects, these factors will have various effects on the efflux and accumulation of arsenic. The definite effects (detoxification or non-detoxification) could be not assured based on the current study, and more systematic and rigorous studies are needed in the future.


Subject(s)
Arsenic Poisoning , Arsenic , Mice , Animals , Fecal Microbiota Transplantation , Arsenic/toxicity , RNA, Ribosomal, 16S/genetics , Feces
19.
Bioresour Technol ; 367: 128241, 2023 Jan.
Article in English | MEDLINE | ID: mdl-36332871

ABSTRACT

Chicken manure is a source of antibiotic resistance genes (ARGs) and pathogenic microbes. Mikania micrantha Kunth (MM) is an invasive plant containing phytochemicals as antimicrobial agents. To explore its impacts on ARGs and pathogen-host interactions (PHIs), MM was added to composting mixtures. The findings indicated that compared with control (CK), MM significantly improved the phytochemical abundances, particularly stilbenoids and diarylheptanoids (4.87%), and ubiquinones (2.66%) in the treatment (T) compost. Besides, significant ARGs reduction was noted, where rpoB2, RbpA, FosB1, vatC, and vatB were removed from T compost. PHIs significantly declined in T compost, where the growth of Xanthomonas citri, Streptococcus pneumoniae, Fusarium graminearum, Vibrio cholerae, and Xanthomonas campestris were inhibited. Multiple variable analyses demonstrated that temperature and pH revealed a significant role in ARGs and PHIs decline. Accordingly, this study considerably recommends MM as a promising compost additive in terms of its antimicrobial potential toward pathogenic microbes and ARGs.


Subject(s)
Composting , Mikania , Animals , Manure/analysis , Chickens/genetics , Anti-Bacterial Agents/pharmacology , Drug Resistance, Microbial/genetics , Genes, Bacterial/genetics , Phytochemicals
20.
Int J Cardiol Heart Vasc ; 43: 101160, 2022 Dec.
Article in English | MEDLINE | ID: mdl-36483149

ABSTRACT

To evaluate the clinical effects of electroacupuncture combined with rehabilitation training (EART) versus conventional rehabilitation training (CRT) on hypertension. Multiple databases like PubMed, Embase, Web of Science and Wanfang database, China National Knowledge Internet database, and Chinese Biological Medical database were used to search for the relevant studies and full-text articles involved in evaluating EART versus CRT with hypertension. Review Manager 5.4 was used to estimate the effects of the results among included articles. Forest plots, sensitivity analysis, and funnel plots were also conducted on the included articles. In this meta-analysis study, there were 9 relevant studies were eventually satisfied the included criteria. There were significant differences between EART group and CRT group in systolic blood pressure after treatment (MD -16.62, 95 %CI = -21.84 to -11.39; P < 0.00001), diastolic blood pressure after treatment (MD = -16.03, 95 % CI = -21.55 to -10.50; P < 0.00001), and effective rate (MD = 1.22, 95 % CI = 1.13 to 1.32; P < 0.00001). Sensitivity analysis and funnel chart demonstrated that the study was robust and limited publication bias was observed. Our data showed that EART was clinically more significant than CRT in hypertension. Further studies need to be performed using large relevance references to verify the effectiveness of EART in the treatment of hypertension.

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