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Phytomedicine : International Journal... Oct 2022With the increasing ages of the general population, the incidence of knee osteoarthritis (KOA) is also rising, and KOA has become a major health problem worldwide.... (Review)
Review
BACKGROUND
With the increasing ages of the general population, the incidence of knee osteoarthritis (KOA) is also rising, and KOA has become a major health problem worldwide. Recently, medicinal plants and their secondary metabolites have gained interest due to their activity in treating KOA. In this paper, a comprehensive systematic review of the literature was performed concerning the effects of medicinal plant extracts and natural compounds against KOA in recent years. The related molecular pathways of natural compounds against KOA were summarized, and the possible crosstalk among components in chondrocytes was discussed to propose possible solutions for the current situation of treating KOA.
PURPOSE
This review focused on the molecular mechanisms by which medicinal plants and their secondary metabolites act against KOA.
METHODS
Literature searches were performed in the PUBMED, Embase, Science Direct, and Web of Science databases for a 10-year period from 2011 to 2022 with the search terms "medicinal plants," "bioactive compounds," "natural products," "phytochemical," "knee osteoarthritis," "knee joint osteoarthritis," "knee osteoarthritis," "osteoarthritis of the knee," and "osteoarthritis of knee joint."
RESULTS
According to the results, substantial plant extracts and secondary metabolites show a positive effect in fighting KOA. Plant extracts and their secondary metabolites can affect the diagnostic and prognostic biomarkers of KOA. Natural products inhibit the expression of MMP1, MMP3, MMP19, syndecan IV, ADAMTS-4, ADAMTS-5, iNOS, COX-2, collagenases, IL-6, IL-1β, and TNF-α in vitro and in vivo and . Cytokines also upregulate the expression of collagen II and aggrecan. The main signaling pathways affected by the extracts and isolated compounds include AMPK, SIRT, NLRP3, MAPKs, PI3K/AKT, mTOR, NF-κB, WNT/β-catenin, JAK/STAT3, and NRF2, as well as the cell death modes apoptosis, autophagy, pyroptosis, and ferroptosis.
CONCLUSION
The role of secondary metabolites in different signaling pathways supplies a better understanding of their potential to develop further curative options for KOA.
Topics: Humans; NF-kappa B; Osteoarthritis, Knee; Phosphatidylinositol 3-Kinases; Plant Extracts; Plants, Medicinal
PubMed: 35914361
DOI: 10.1016/j.phymed.2022.154347 -
The Cochrane Database of Systematic... Feb 2023Since the previous Cochrane Review on this topic in 2016, debate has continued surrounding a potential role for vitamin D in reducing risk of asthma exacerbation and... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Since the previous Cochrane Review on this topic in 2016, debate has continued surrounding a potential role for vitamin D in reducing risk of asthma exacerbation and improving asthma control. We therefore conducted an updated meta-analysis to include data from new trials completed since this date.
OBJECTIVES
To evaluate the effectiveness and safety of administration of vitamin D or its hydroxylated metabolites in reducing the risk of severe asthma exacerbations (defined as those requiring treatment with systemic corticosteroids) and improving asthma symptom control.
SEARCH METHODS
We searched the Cochrane Airways Group Trial Register and reference lists of articles. We contacted the authors of studies in order to identify additional trials. Date of last search: 8 September 2022.
SELECTION CRITERIA
We included double-blind, randomised, placebo-controlled trials of vitamin D in children and adults with asthma evaluating exacerbation risk or asthma symptom control, or both.
DATA COLLECTION AND ANALYSIS
Four review authors independently applied study inclusion criteria, extracted the data, and assessed risk of bias. We obtained missing data from the authors where possible. We reported results with 95% confidence intervals (CIs). The primary outcome was the incidence of severe asthma exacerbations requiring treatment with systemic corticosteroids. Secondary outcomes included the incidence of asthma exacerbations precipitating an emergency department visit or requiring hospital admission, or both, end-study childhood Asthma Control Test (cACT) or Asthma Control Test (ACT) scores, and end-study % predicted forced expiratory volume in one second (FEV1). We performed subgroup analyses to determine whether the effect of vitamin D on risk of asthma exacerbation was modified by baseline vitamin D status, vitamin D dose, frequency of dosing regimen, form of vitamin D given, and age of participants.
MAIN RESULTS
We included 20 studies in this review; 15 trials involving a total of 1155 children and five trials involving a total of 1070 adults contributed data to analyses. Participant ages ranged from 1 to 84 years, with two trials providing data specific to participants under five years (n = 69) and eight trials providing data specific to participants aged 5 to 16 (n = 766). Across the trials, 1245 participants were male and 1229 were female, with two studies not reporting sex distribution. Fifteen trials contributed to the primary outcome analysis of exacerbations requiring systemic corticosteroids. The duration of trials ranged from three to 40 months; all but two investigated effects of administering cholecalciferol (vitamin D3). As in the previous Cochrane Review, the majority of participants had mild to moderate asthma, and profound vitamin D deficiency (25-hydroxyvitamin D (25(OH)D) < 25 nmol/L) at baseline was rare. Administration of vitamin D or its hydroxylated metabolites did not reduce or increase the proportion of participants experiencing one or more asthma exacerbations treated with systemic corticosteroids (odds ratio (OR) 1.04, 95% CI 0.81 to 1.34; I = 0%; 14 studies, 1778 participants; high-quality evidence). This equates to an absolute risk of 226 per 1000 (95% CI 185 to 273) in the pooled vitamin D group, compared to a baseline risk of 219 participants per 1000 in the pooled placebo group. We also found no effect of vitamin D supplementation on the rate of exacerbations requiring systemic corticosteroids (rate ratio 0.86, 95% CI 0.62 to 1.19; I = 60%; 10 studies, 1599 participants; high-quality evidence), or the time to first exacerbation (hazard ratio 0.82, 95% CI 0.59 to 1.15; I = 22%; 3 studies, 850 participants; high-quality evidence). Subgroup analysis did not reveal any evidence of effect modification by baseline vitamin D status, vitamin D dose, frequency of dosing regimen, or age. A single trial investigating administration of calcidiol reported a benefit of the intervention for the primary outcome of asthma control. Vitamin D supplementation did not influence any secondary efficacy outcome meta-analysed, which were all based on moderate- or high-quality evidence. We observed no effect on the incidence of serious adverse events (OR 0.89, 95% CI 0.56 to 1.41; I = 0%; 12 studies, 1556 participants; high-quality evidence). The effect of vitamin D on fatal asthma exacerbations was not estimable, as no such events occurred in any trial. Six studies reported adverse reactions potentially attributable to vitamin D. These occurred across treatment and control arms and included hypercalciuria, hypervitaminosis D, kidney stones, gastrointestinal symptoms and mild itch. In one trial, we could not ascertain the total number of participants with hypercalciuria from the trial report. We assessed three trials as being at high risk of bias in at least one domain; none of these contributed data to the analysis of the outcomes reported above. Sensitivity analyses that excluded these trials from each outcome to which they contributed did not change the null findings.
AUTHORS' CONCLUSIONS
In contrast to findings of our previous Cochrane Review on this topic, this updated review does not find evidence to support a role for vitamin D supplementation or its hydroxylated metabolites to reduce risk of asthma exacerbations or improve asthma control. Participants with severe asthma and those with baseline 25(OH)D concentrations < 25 nmol/L were poorly represented, so further research is warranted here. A single study investigating effects of calcidiol yielded positive results, so further studies investigating effects of this metabolite are needed.
Topics: Adult; Child; Humans; Male; Female; Infant; Child, Preschool; Adolescent; Young Adult; Middle Aged; Aged; Aged, 80 and over; Calcifediol; Hypercalciuria; Disease Progression; Asthma; Vitamins; Adrenal Cortex Hormones; Vitamin D; Cholecalciferol; Anti-Asthmatic Agents; Randomized Controlled Trials as Topic
PubMed: 36744416
DOI: 10.1002/14651858.CD011511.pub3 -
Journal of Human Kinetics Aug 2019Beta-hydroxy-beta-methylbutyrate (HMB) has been used extensively as a dietary supplement for athletes and physically active people. HMB is a leucine metabolite, which is...
Beta-hydroxy-beta-methylbutyrate (HMB) has been used extensively as a dietary supplement for athletes and physically active people. HMB is a leucine metabolite, which is one of three branched chain amino acids. HMB plays multiple roles in the human body of which most important ones include protein metabolism, insulin activity and skeletal muscle hypertrophy. The ergogenic effects of HMB supplementation are related to the enhancement of sarcolemma integrity, inhibition of protein degradation (ubiquitin pathway), decreased cell apoptosis, increased protein synthesis (mTOR pathway), stimulation of the growth hormone/insulin-like growth factor-1 (GH/IGF-1) axis and enhancement of muscle stem cells proliferation and differentiation. HMB supplementation has been carried out with various groups of athletes. In endurance and martial arts athletes, HMB supplementation revealed positive effects on specific aerobic capacity variables. Positive results were also disclosed in resistance trained athletes, where changes in strength, body fat and muscle mass as well as anaerobic performance and power output were observed. The purpose of this review was to present the main mechanisms of HMB action, especially related to muscle protein synthesis and degradation, and ergogenic effects on different types of sports and physical activities.
PubMed: 31531146
DOI: 10.2478/hukin-2019-0070 -
Nutrients Apr 2020Endocrine disruptors (EDCs) have been associated with the increased incidence of metabolic disorders. In this work, we conducted a systematic review of the literature in...
Endocrine disruptors (EDCs) have been associated with the increased incidence of metabolic disorders. In this work, we conducted a systematic review of the literature in order to identify the current knowledge of the interactions between EDCs in food, the gut microbiota, and metabolic disorders in order to shed light on this complex triad. Exposure to EDCs induces a series of changes including microbial dysbiosis and the induction of xenobiotic pathways and associated genes, enzymes, and metabolites involved in EDC metabolism. The products and by-products released following the microbial metabolism of EDCs can be taken up by the host; therefore, changes in the composition of the microbiota and in the production of microbial metabolites could have a major impact on host metabolism and the development of diseases. The remediation of EDC-induced changes in the gut microbiota might represent an alternative course for the treatment and prevention of metabolic diseases.
Topics: Dysbiosis; Endocrine Disruptors; Food Analysis; Gastrointestinal Microbiome; Humans; Metabolic Diseases
PubMed: 32326280
DOI: 10.3390/nu12041158 -
Cancer Science Jul 2021Chemotherapy for non-Hodgkin lymphoma (NHL) in the hemodialysis (HD) patient is a challenging situation. Because many drugs are predominantly eliminated by the kidneys,...
Chemotherapy for non-Hodgkin lymphoma (NHL) in the hemodialysis (HD) patient is a challenging situation. Because many drugs are predominantly eliminated by the kidneys, chemotherapy in the HD patient requires special considerations concerning dose adjustments to avoid overdose and toxicities. Conversely, some drugs are removed by HD and may expose the patient to undertreatment, therefore the timing of drug administration in relation to HD sessions must be carefully planned. Also, the metabolites of some drugs show different toxicities and dialysability as compared with the parent drug, therefore this must also be catered for. However, the pharmacokinetics of many chemotherapeutics and their metabolites in HD patients are unknown, and the fact that NHL patients are often treated with distinct multiagent chemotherapy regimens makes the situation more complicated. In a realm where uncertainty prevails, case reports and case series reporting on actual treatment and outcomes are extremely valuable and can aid physicians in decision making from drug selection to dosing. We carried out an exhaustive review of the literature and adopted 48 manuscripts consisting of 66 HD patients undergoing 71 chemotherapy regimens for NHL, summarized the data, and provide recommendations concerning dose adjustments and timing of administration for individual chemotherapeutics where possible. The chemotherapy regimens studied in this review include, but are not limited to, rituximab, cyclophosphamide + vincristine + prednisolone (CVP) and cyclophosphamide + doxorubicin + vincristine + prednisolone (CHOP)-like regimens, chlorambucil, ibrutinib, bendamustine, methotrexate, platinum compounds, cytarabine, gemcitabine, etoposide, ifosfamide, melphalan, busulfan, fludarabine, mogamulizumab, brentuximab vedotin, and Y-ibritumomab tiuxetan.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Child; Cyclophosphamide; Doxorubicin; Drug Administration Schedule; Female; Hematopoietic Stem Cell Transplantation; Humans; Kidney; Lymphoma, Non-Hodgkin; Male; Middle Aged; Prednisone; Renal Dialysis; Rituximab; Vincristine; Young Adult
PubMed: 33938097
DOI: 10.1111/cas.14933 -
Frontiers in Pharmacology 2021Crocetin is an aglycone of crocin naturally occurring in saffron and produced in biological systems by hydrolysis of crocin as a bioactive metabolite. It is known to... (Review)
Review
Crocetin is an aglycone of crocin naturally occurring in saffron and produced in biological systems by hydrolysis of crocin as a bioactive metabolite. It is known to exist in several medicinal plants, the desiccative ripe fruit of the cape jasmine belonging to the Rubiaceae family, and stigmas of the saffron plant of the Iridaceae family. According to modern pharmacological investigations, crocetin possesses cardioprotective, hepatoprotective, neuroprotective, antidepressant, antiviral, anticancer, atherosclerotic, antidiabetic, and memory-enhancing properties. Although poor bioavailability hinders therapeutic applications, derivatization and formulation preparation technologies have broadened the application prospects for crocetin. To promote the research and development of crocetin, we summarized the distribution, preparation and production, total synthesis and derivatization technology, pharmacological activity, pharmacokinetics, drug safety, drug formulations, and preparation of crocetin.
PubMed: 35095483
DOI: 10.3389/fphar.2021.745683 -
Journal of Agricultural and Food... Aug 2023Berries are rich in (poly)phenols, and these compounds may be beneficial to human health. Estimating berry consumption through self-reported questionnaires has been... (Review)
Review
Berries are rich in (poly)phenols, and these compounds may be beneficial to human health. Estimating berry consumption through self-reported questionnaires has been challenging due to compliance issues and a lack of precision. Estimation via food-derived biomarkers in biofluids was proposed as a complementary alternative. We aimed to review and update the existing evidence on biomarkers of intake for six different types of berries. A systematic literature search was performed to update a previous systematic review on PubMed, Web of Science, and Scopus from January 2020 until December 2022. Out of 42 papers, only 18 studies were eligible. A multimetabolite panel is suggested for blueberry and cranberry intake. Proposed biomarkers for blueberries include hippuric acid and malvidin glycosides. For cranberries, suggested biomarkers are glycosides of peonidin and cyanidin together with sulfate and glucuronide conjugates of phenyl-γ-valerolactone derivatives. No new metabolite candidates have been found for raspberries, strawberries, blackcurrants, and blackberries. Further studies are encouraged to validate these multimetabolite panels for improving the estimation of berry consumption.
Topics: Humans; Fruit; Fragaria; Rubus; Blueberry Plants; Glycosides; Vaccinium macrocarpon
PubMed: 37499164
DOI: 10.1021/acs.jafc.3c01142 -
Archives of Medical Research Feb 2023Gastric cancer (GC) is often diagnosed at an advanced stage and thus patients have a poor prognosis. This implies that early detection of this cancer will improve... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Gastric cancer (GC) is often diagnosed at an advanced stage and thus patients have a poor prognosis. This implies that early detection of this cancer will improve patient prognosis and survival. This systematic review explored the association of circulating protein and metabolite biomarkers with GC development.
METHODS
A literature search was conducted until November 2021 on Medline, Embase, Cochrane library, and Web of Science databases. Studies were included if they assessed circulating proteins and metabolites in blood, urine, or saliva and determined their association with GC risk. Quality of identified studies was determined using the Newcastle-Ottawa scale for cohort studies. Random and fixed effects meta-analyses were performed to calculate pooled odds ratio.
RESULTS
A total of 53 studies were included. High levels of anti-Helicobacter pylORi IgG levels, pepsinogen I (PGI) <30 µg/L and serum pepsinogen I/ pepsinogen II (PGI/II) ratio<3 were positively associated with risk of developing GC (pooled odds ratio (OR): 2.70; 95% CI: 1.44-5.04, 5.96, 95% CI: 2.65-13.42 and 4.43; 95% CI: 3.04-6.47). In addition, an inverse relationship was found between ferritin, iron and transferrin levels and risk of developing GC (OR: 0.62; 95% CI: 0.38-1,0.97; 95% CI: 0.94-1 and 0.85; 95% CI: 0.76-0.94). However, there was no association between levels of glucose, cholesterol, vitamin C, vitamin B12, vitamin A, α-Carotene, β-Carotene, α-Tocopherol, γ-Tocopherol, and GC risk.
CONCLUSION
The pooled analysis demonstrated that high levels of anti-Helicobacter pylORi IgG, PGI<30µg/L and serum PGI/II ratio <3 and low levels of ferritin, iron and transferrin were associated with risk of GC.
Topics: Humans; Stomach Neoplasms; Pepsinogen A; Biomarkers; Pepsinogen C; Immunoglobulin G; Ferritins; Iron; Transferrins; Helicobacter Infections
PubMed: 36759293
DOI: 10.1016/j.arcmed.2022.12.012 -
Nutrients Nov 2023Multiple studies have indicated that distinct metabolites are involved in the occurrence and development of osteopenia (ON) and osteoporosis (OP); however, these... (Meta-Analysis)
Meta-Analysis Review
Multiple studies have indicated that distinct metabolites are involved in the occurrence and development of osteopenia (ON) and osteoporosis (OP); however, these metabolites in OP and ON have not yet been classified and standardized. This systematic review and meta-analysis included 21 articles aiming to investigate the distinct metabolites in patients with ON and OP. The quality of the included articles was generally high; seventeen studies had >7 stars, and the remaining four received 6 stars. This systematic review showed that three metabolites (phosphatidylcholine (PC) (lipid metabolites), galactose (carbohydrate metabolites), and succinic acid (other metabolites)) increased, four (glycylglycine (gly-gly), cystine (amino acids), sphingomyelin (SM) (lipid metabolites) and glucose (carbohydrate metabolites)) decreased, and five (glutamine, hydroxyproline, taurine (amino acids), lysophosphatidylcholine (LPC) (lipid metabolites), and lactate (other metabolites)) had conflicting directions in OP/ON. The results of the meta-analysis show that gly-gly (MD = -0.77, 95%CI -1.43 to -0.11, = 0.02) and cystine (MD = -5.52, 95%CI -7.35 to -3.68, < 0.00001) decreased in the OP group compared with the healthy control group. Moreover, LPC (MD = 1.48, 95%CI 0.11 to 2.86, = 0.03) increased in the OP group compared with the healthy control group. These results indicate that distinct metabolites were associated with ON and OP, which could be considered a predictor for OP.
Topics: Humans; Cystine; Osteoporosis; Bone Diseases, Metabolic; Amino Acids; Lysophosphatidylcholines; Carbohydrates
PubMed: 38068753
DOI: 10.3390/nu15234895 -
Journal of Investigative Medicine : the... Aug 2023The therapeutic response heterogeneity in acromegaly persists, despite the medical-surgical advances of recent years. Thus, personalized medicine implementation, which... (Review)
Review
The therapeutic response heterogeneity in acromegaly persists, despite the medical-surgical advances of recent years. Thus, personalized medicine implementation, which focuses on each patient, is justified. Metabolomics would decipher the molecular mechanisms underlying the therapeutic response heterogeneity. Identification of altered metabolic pathways would open new horizons in the therapeutic management of acromegaly. This research aimed to evaluate the metabolomic profile in acromegaly and metabolomics' contributions to understanding disease pathogenesis. A systematic review was carried out by querying four electronic databases and evaluating patients with acromegaly through metabolomic techniques. In all, 21 studies containing 362 patients were eligible. Choline, the ubiquitous metabolite identified in growth hormone (GH)-secreting pituitary adenomas (Pas) by in vivo magnetic resonance spectroscopy (MRS), negatively correlated with somatostatin receptors type 2 expression and positively correlated with magnetic resonance imaging T2 signal and Ki-67 index. Moreover, elevated choline and choline/creatine ratio differentiated between sparsely and densely granulated GH-secreting PAs. MRS detected low hepatic lipid content in active acromegaly, which increased after disease control. The panel of metabolites of acromegaly deciphered by mass spectrometry (MS)-based techniques mainly included amino acids (especially branched-chain amino acids and taurine), glyceric acid, and lipids. The most altered pathways in acromegaly were the metabolism of glucose (particularly the downregulation of the pentose phosphate pathway), linoleic acid, sphingolipids, glycerophospholipids, arginine/proline, and taurine/hypotaurine. Matrix-assisted laser desorption/ionization coupled with MS imaging confirmed the functional nature of GH-secreting PAs and accurately discriminated PAs from healthy pituitary tissue.
Topics: Humans; Acromegaly; Growth Hormone-Secreting Pituitary Adenoma; Magnetic Resonance Imaging; Metabolomics; Adenoma
PubMed: 37139720
DOI: 10.1177/10815589231169452