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Frontiers in Immunology 2022Mammalian neuraminidases (NEUs), also known as sialidases, are enzymes that cleave off the terminal neuraminic, or sialic, acid resides from the carbohydrate moieties of...
Mammalian neuraminidases (NEUs), also known as sialidases, are enzymes that cleave off the terminal neuraminic, or sialic, acid resides from the carbohydrate moieties of glycolipids and glycoproteins. A rapidly growing body of literature indicates that in addition to their metabolic functions, NEUs also regulate the activity of their glycoprotein targets. The simple post-translational modification of NEU protein targets-removal of the highly electronegative sialic acid-affects protein folding, alters protein interactions with their ligands, and exposes or covers proteolytic sites. Through such effects, NEUs regulate the downstream processes in which their glycoprotein targets participate. A major target of desialylation by NEUs are mucins (MUCs), and such post-translational modification contributes to regulation of disease processes. In this review, we focus on the regulatory roles of NEU-modified MUCs as coordinators of disease pathogenesis in fibrotic, inflammatory, infectious, and autoimmune diseases. Special attention is placed on the most abundant and best studied NEU1, and its recently discovered important target, mucin-1 (MUC1). The role of the NEU1 - MUC1 axis in disease pathogenesis is discussed, along with regulatory contributions from other MUCs and other pathophysiologically important NEU targets.
Topics: Animals; Glycoproteins; Immune System Diseases; Mammals; Mucins; N-Acetylneuraminic Acid; Neuraminidase
PubMed: 35479093
DOI: 10.3389/fimmu.2022.883079 -
BMJ Open Apr 2022To determine the accuracy of metabolomics in predicting hypertensive disorders in pregnancy.
OBJECTIVE
To determine the accuracy of metabolomics in predicting hypertensive disorders in pregnancy.
DESIGN
Systematic review of observational studies.
DATA SOURCES AND STUDY ELIGIBILITY CRITERIA
An electronic literature search was performed in June 2019 and February 2022. Two researchers independently selected studies published between 1998 and 2022 on metabolomic techniques applied to predict the condition; subsequently, they extracted data and performed quality assessment. Discrepancies were dealt with a third reviewer. The primary outcome was pre-eclampsia. Cohort or case-control studies were eligible when maternal samples were taken before diagnosis of the hypertensive disorder.
STUDY APPRAISAL AND SYNTHESIS METHODS
Data on study design, maternal characteristics, how hypertension was diagnosed, metabolomics details and metabolites, and accuracy were independently extracted by two authors.
RESULTS
Among 4613 initially identified studies on metabolomics, 68 were read in full text and 32 articles were included. Studies were excluded due to duplicated data, study design or lack of identification of metabolites. Metabolomics was applied mainly in the second trimester; the most common technique was liquid-chromatography coupled to mass spectrometry. Among the 122 different metabolites found, there were 23 amino acids and 21 fatty acids. Most of the metabolites were involved with ammonia recycling; amino acid metabolism; arachidonic acid metabolism; lipid transport, metabolism and peroxidation; fatty acid metabolism; cell signalling; galactose metabolism; nucleotide sugars metabolism; lactose degradation; and glycerolipid metabolism. Only citrate was a common metabolite for prediction of early-onset and late-onset pre-eclampsia. Vitamin D was the only metabolite in common for pre-eclampsia and gestational hypertension prediction. Meta-analysis was not performed due to lack of appropriate standardised data.
CONCLUSIONS AND IMPLICATIONS
Metabolite signatures may contribute to further insights into the pathogenesis of pre-eclampsia and support screening tests. Nevertheless, it is mandatory to validate such methods in larger studies with a heterogeneous population to ascertain the potential for their use in clinical practice.
PROSPERO REGISTRATION NUMBER
CRD42018097409.
Topics: Case-Control Studies; Female; Humans; Hypertension, Pregnancy-Induced; Mass Spectrometry; Metabolomics; Pre-Eclampsia; Pregnancy
PubMed: 35470187
DOI: 10.1136/bmjopen-2021-054697 -
Journal of Infection and Chemotherapy :... Feb 2022The aim of this study was to use a network meta-analysis (NWA) to evaluate the relative efficacy and safety of various neuraminidase inhibitors (NAIs) in reducing the... (Meta-Analysis)
Meta-Analysis Review
The aim of this study was to use a network meta-analysis (NWA) to evaluate the relative efficacy and safety of various neuraminidase inhibitors (NAIs) in reducing the duration of influenza symptoms, and thereby, informing the selection of suitable therapeutic regimens for patients with influenza. We conducted a systematic review of randomized controlled trials comparing the clinical effects of four NAIs administered to patients with influenza and placebo. Relevant studies were found in the PubMed and Cochrane databases. Unpublished studies were collected from the ClinicalTrials.gov registry and through hand searching. We carried out NWA to compare the different regimens with each other and across subgroups of age and medical status (high-risk patients). A total of 58 two-arm studies were identified. Five regimens were efficacious in reducing the time to alleviation of influenza symptoms in all populations; this efficacy was comparable. No significant improvements were seen in combination therapy groups. The mean difference in the time to alleviation of symptoms ranged from 12.78 to 19.51 h. According to the summarized mean difference and surface under the cumulative ranking curve (SUCRA), peramivir (SUCRA = 82.6%), zanamivir (SUCRA = 64%), and oseltamivir (SUCRA = 55.1%) were the three top-ranking drugs for treating influenza. Zanamivir and peramivir were the preferred pharmacologic intervention among all investigated interventions based on the calculated "value preference of SUCRA." This study is a network meta-analysis to explore the therapeutic effects of NAIs in patients with influenza. Peramivir might be the best choice for reducing the time to alleviation of symptoms.
Topics: Antiviral Agents; Enzyme Inhibitors; Guanidines; Humans; Influenza, Human; Network Meta-Analysis; Neuraminidase; Oseltamivir; Zanamivir
PubMed: 34840038
DOI: 10.1016/j.jiac.2021.11.014 -
Nutrients Aug 2021The aim of this systematic review was to summarize concentrations of human milk oligosaccharides (HMOs) in the Chinese population. We searched articles originally... (Meta-Analysis)
Meta-Analysis
The aim of this systematic review was to summarize concentrations of human milk oligosaccharides (HMOs) in the Chinese population. We searched articles originally published in both Chinese and English. When compiling data, lactation was categorized into five stages. We found that 6'-sialyllactose, lacto--tetraose, and lacto--neotetraose decreased over lactation. Conversely, 3'-fucosyllactose increased over lactation. Our study represents the first systematic review to summarize HMO concentrations in Chinese population. Our findings not only provide data on HMO profiles in Chinese population but suggest future directions in the study of the metabolism of HMOs.
Topics: Breast Feeding; China; Female; Fucose; Humans; Lactation; Lactose; Milk, Human; Oligosaccharides; Sialic Acids
PubMed: 34578788
DOI: 10.3390/nu13092912 -
JAMA Network Open Aug 2021Antiviral treatment of influenza is recommended for patients with influenza-like illness during periods of community cocirculation of influenza viruses and SARS-CoV-2;... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Antiviral treatment of influenza is recommended for patients with influenza-like illness during periods of community cocirculation of influenza viruses and SARS-CoV-2; however, questions remain about which treatment is associated with the best outcomes and fewest adverse events.
OBJECTIVE
To compare the efficacy and safety of neuraminidase inhibitors and the endonuclease inhibitor for the treatment of seasonal influenza among healthy adults and children.
DATA SOURCES
Medline, Embase, and the Cochrane Register of Clinical Trials were searched from inception to January 2020 (the last search was updated in October 2020).
STUDY SELECTION
Included studies were randomized clinical trials conducted among patients of all ages with influenza treated with neuraminidase inhibitors (ie, oseltamivir, peramivir, zanamivir, or laninamivir) or an endonuclease inhibitor (ie, baloxavir) compared with other active agents or placebo.
DATA EXTRACTION AND SYNTHESIS
Two investigators identified studies and independently abstracted data. Frequentist network meta-analyses were performed; relative ranking of agents was conducted using P-score probabilities. Quality of evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluations criteria. Data were analyzed in October 2020.
MAIN OUTCOMES AND MEASURES
The time to alleviation of influenza symptoms (TTAS), complications of influenza, and adverse events (total adverse events, nausea, and vomiting).
RESULTS
A total of 26 trials were identified that investigated antiviral drugs at high or low doses; these trials included 11 897 participants, among whom 6294 (52.9%) were men and the mean (SD) age was 32.5 (16.9) years. Of all treatments comparing with placebo in efficacy outcomes, high-quality evidence indicated that zanamivir was associated with the shortest TTAS (hazard ratio, 0.67; 95% CI, 0.58-0.77), while baloxavir was associated with the lowest risk of influenza-related complications (risk ratio [RR], 0.51; 95% CI, 0.32-0.80) based on moderate-quality evidence. In safety outcomes, baloxavir was associated with the lowest risk of total adverse events (RR, 0.84; 95% CI, 0.74-0.96) compared with placebo based on moderate-quality evidence. There was no strong evidence of associations with risk of nausea or vomiting among all comparisons, except for 75 mg oseltamivir, which was associated with greater occurrence of nausea (RR, 1.82; 95% CI, 1.38-2.41) and vomiting (RR, 1.88; 95% CI, 1.47-2.41).
CONCLUSIONS AND RELEVANCE
In this systematic review and network meta-analysis, all 4 antiviral agents assessed were associated with shortening TTAS; zanamivir was associated with the shortest TTAS, and baloxavir was associated with reduced rate of influenza-related complications.
Topics: Adolescent; Adult; Antiviral Agents; Child; Dibenzothiepins; Endonucleases; Enzyme Inhibitors; Female; Humans; Influenza A virus; Influenza, Human; Male; Middle Aged; Morpholines; Network Meta-Analysis; Neuraminidase; Pyridones; Randomized Controlled Trials as Topic; Seasons; Triazines; Young Adult; Zanamivir
PubMed: 34387680
DOI: 10.1001/jamanetworkopen.2021.19151 -
Biomedicine & Pharmacotherapy =... Sep 2021Depressive disorder is a kind of emotional disorder that is mainly manifested with spontaneous and persistent low mood. Its etiology is complex and still not fully...
Depressive disorder is a kind of emotional disorder that is mainly manifested with spontaneous and persistent low mood. Its etiology is complex and still not fully understood. Metabolomics, an important part of system biology characterized by its integrity and systematicness, analyzes endogenous metabolites of small molecules in vivo and examines the metabolic status of the organism. It is widely used in the field of disease research for its unique advantage in the disease molecular marker discovering Due to fewer adverse reactions and high safety, Chinese herbal medicine (CHM) has great advantages in the treatment of chronic diseases including depression. Metabolomics has been gradually applied to the efficacy evaluation of CHM in treatment of depression and the metabolomics analysis exhibits a systemic metabolic shift in amino acids (such as alanine, glutamic acid, valine, etc.), organic acids (lactic acid, citric acid, stearic acid, palmitic acid, etc.), and sugars, amines, etc. These differential metabolites are mainly involved in energy metabolism, amino acid metabolism, lipid metabolism, etc. In this review, we have exemplified the study of CHM in animals or clinics on the depression, and revealed that CHM treatment has significantly changed the metabolic disorders associated with depression, promoting metabolic network reorganization through restoring of key metabolites, and metabolic pathways, which may be the main mechanism basis of CHM's treatment on depression. Besides, we further envisioned the future application of metabolomics in the study of CHM treatment of depression.
Topics: Animals; Depressive Disorder; Drugs, Chinese Herbal; Humans; Medicine, Chinese Traditional; Metabolomics
PubMed: 34225013
DOI: 10.1016/j.biopha.2021.111866 -
Frontiers in Plant Science 2021Temperature, water, solar radiation, and atmospheric CO concentration are the main abiotic factors that are changing in the course of global warming. These abiotic...
Temperature, water, solar radiation, and atmospheric CO concentration are the main abiotic factors that are changing in the course of global warming. These abiotic factors govern the synthesis and degradation of primary (sugars, amino acids, organic acids, etc.) and secondary (phenolic and volatile flavor compounds and their precursors) metabolites directly, via the regulation of their biosynthetic pathways, or indirectly, via their effects on vine physiology and phenology. Several hundred secondary metabolites have been identified in the grape berry. Their biosynthesis and degradation have been characterized and have been shown to occur during different developmental stages of the berry. The understanding of how the different abiotic factors modulate secondary metabolism and thus berry quality is of crucial importance for breeders and growers to develop plant material and viticultural practices to maintain high-quality fruit and wine production in the context of global warming. Here, we review the main secondary metabolites of the grape berry, their biosynthesis, and how their accumulation and degradation is influenced by abiotic factors. The first part of the review provides an update on structure, biosynthesis, and degradation of phenolic compounds (flavonoids and non-flavonoids) and major aroma compounds (terpenes, thiols, methoxypyrazines, and C13 norisoprenoids). The second part gives an update on the influence of abiotic factors, such as water availability, temperature, radiation, and CO concentration, on berry secondary metabolism. At the end of the paper, we raise some critical questions regarding intracluster berry heterogeneity and dilution effects and how the sampling strategy can impact the outcome of studies on the grapevine berry response to abiotic factors.
PubMed: 33828576
DOI: 10.3389/fpls.2021.643258 -
Acta Diabetologica Aug 2021Diabetic kidney disease is the leading cause of end-stage kidney disease in high-income countries. The strict control of glycemic oscillations is the principal...
Diabetic kidney disease is the leading cause of end-stage kidney disease in high-income countries. The strict control of glycemic oscillations is the principal therapeutic target, but this could be hard to achieve in uremic patients due to their unpredictable insulin sensitivity. Currently, the evaluation of the glycemic profile relies on serum markers (glycated hemoglobin HbA1c, glycated albumin, and fructosamine), capillary glucose blood control (self-monitoring of blood glucose), and interstitial glucose control (continue glucose monitoring). We conducted a systematic review of published articles on continue glucose monitoring in hemodialysis patients with type 2 diabetes, which included 12 major articles. Four studies found significant fluctuations in glucose levels during hemodialysis sessions. All studies reported a higher mean amplitude of glucose variations on the hemodialysis day. Three studies agreed that continue glucose monitoring is better than glycated hemoglobin in detecting these abnormalities. Moreover, continue glucose monitoring was more accurate and perceived as easier to use by patients and their caregivers. In patients with type 2 diabetes on hemodialysis, glucose levels show different variation patterns than the patients on hemodialysis without diabetes. Considering manageability, accuracy, and cost-effectiveness, continue glucose monitoring could be the ideal diagnostic tool for the patient with diabetes on hemodialysis.
Topics: Aged; Biomarkers; Blood Glucose; Blood Glucose Self-Monitoring; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Female; Fructosamine; Glycated Hemoglobin; Glycation End Products, Advanced; Glycemic Control; Humans; Kidney Failure, Chronic; Male; Middle Aged; Renal Dialysis; Serum Albumin; Glycated Serum Albumin
PubMed: 33743082
DOI: 10.1007/s00592-021-01699-6 -
Nutrition & Metabolism 2020Diabetes mellitus is one of the most important threats to human health in the twenty-first century. The use of complementary and alternative medicine to prevent,... (Review)
Review
Diabetes mellitus is one of the most important threats to human health in the twenty-first century. The use of complementary and alternative medicine to prevent, control, and reduce the complications of diabetes mellitus is increasing at present. Glutamine amino acid is known as a functional food. The purpose of this systematic review is to determine the potential role of glutamine supplementation on metabolic variables in diabetes mellitus. For this review, PubMed, SCOPUS, Embase, ProQuest, and Google Scholar databases were searched from inception through April 2020. All clinical trial and animal studies assessing the effects of glutamine on diabetes mellitus were eligible for inclusion. 19 studies of 1482 articles met the inclusion criteria. Of the 19 studies, nine studies reported a significant increase in serum GLP-1 levels. Also, eight studies showed reducing in serum levels of fasting blood sugar, four studies reducing in postprandial blood sugar, and triglyceride after glutamine supplementation. Although glutamine resulted in a significant increase in insulin production in seven studies, the findings on Hb-A1c levels were inconclusive. In addition to, despite of the results was promising for the effects of glutamine on weight changes, oxidative stress, and inflammation, more precise clinical trials are needed to obtain more accurate results. In conclusion, glutamine supplementation could improve glycemic control and levels of incretins (such as GLP-1 and GIP) in diabetes mellitus. However, more studies are needed for future studies.
PubMed: 32983244
DOI: 10.1186/s12986-020-00503-6 -
The Cochrane Database of Systematic... Aug 2020On the American continent, cutaneous and mucocutaneous leishmaniasis (CL and MCL) are diseases associated with infection by several species of Leishmania parasites.... (Meta-Analysis)
Meta-Analysis
BACKGROUND
On the American continent, cutaneous and mucocutaneous leishmaniasis (CL and MCL) are diseases associated with infection by several species of Leishmania parasites. Pentavalent antimonials remain the first-choice treatment. There are alternative interventions, but reviewing their effectiveness and safety is important as availability is limited. This is an update of a Cochrane Review first published in 2009.
OBJECTIVES
To assess the effects of interventions for all immuno-competent people who have American cutaneous and mucocutaneous leishmaniasis (ACML).
SEARCH METHODS
We updated our database searches of the Cochrane Skin Group Specialised Register, CENTRAL, MEDLINE, Embase, LILACS and CINAHL to August 2019. We searched five trials registers.
SELECTION CRITERIA
Randomised controlled trials (RCTs) assessing either single or combination treatments for ACML in immuno-competent people, diagnosed by clinical presentation and Leishmania infection confirmed by smear, culture, histology, or polymerase chain reaction on a biopsy specimen. The comparators were either no treatment, placebo only, or another active compound.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures expected by Cochrane. Our key outcomes were the percentage of participants 'cured' at least three months after the end of treatment, adverse effects, and recurrence. We used GRADE to assess evidence certainty for each outcome.
MAIN RESULTS
We included 75 studies (37 were new), totalling 6533 randomised participants with ATL. The studies were mainly conducted in Central and South America at regional hospitals, local healthcare clinics, and research centres. More male participants were included (mean age: roughly 28.9 years (SD: 7.0)). The most common confirmed species were L. braziliensis, L. panamensis, and L. mexicana. The most assessed interventions and comparators were non-antimonial systemics (particularly oral miltefosine) and antimonials (particularly meglumine antimoniate (MA), which was also a common intervention), respectively. Three studies included moderate-to-severe cases of mucosal leishmaniasis but none included cases with diffuse cutaneous or disseminated CL, considered the severe cutaneous form. Lesions were mainly ulcerative and located in the extremities and limbs. The follow-up (FU) period ranged from 28 days to 7 years. All studies had high or unclear risk of bias in at least one domain (especially performance bias). None of the studies reported the degree of functional or aesthetic impairment, scarring, or quality of life. Compared to placebo, at one-year FU, intramuscular (IM) MA given for 20 days to treat L. braziliensis and L. panamensis infections in ACML may increase the likelihood of complete cure (risk ratio (RR) 4.23, 95% confidence interval (CI) 0.84 to 21.38; 2 RCTs, 157 participants; moderate-certainty evidence), but may also make little to no difference, since the 95% CI includes the possibility of both increased and reduced healing (cure rates), and IMMA probably increases severe adverse effects such as myalgias and arthralgias (RR 1.51, 95% CI 1.17 to 1.96; 1 RCT, 134 participants; moderate-certainty evidence). IMMA may make little to no difference to the recurrence risk, but the 95% CI includes the possibility of both increased and reduced risk (RR 1.79, 95% CI 0.17 to 19.26; 1 RCT, 127 participants; low-certainty evidence). Compared to placebo, at six-month FU, oral miltefosine given for 28 days to treat L. mexicana, L. panamensis and L. braziliensis infections in American cutaneous leishmaniasis (ACL) probably improves the likelihood of complete cure (RR 2.25, 95% CI 1.42 to 3.38), and probably increases nausea rates (RR 3.96, 95% CI 1.49 to 10.48) and vomiting (RR 6.92, 95% CI 2.68 to 17.86) (moderate-certainty evidence). Oral miltefosine may make little to no difference to the recurrence risk (RR 2.97, 95% CI 0.37 to 23.89; low-certainty evidence), but the 95% CI includes the possibility of both increased and reduced risk (all based on 1 RCT, 133 participants). Compared to IMMA, at 6 to 12 months FU, oral miltefosine given for 28 days to treat L. braziliensis, L. panamensis, L. guyanensis and L. amazonensis infections in ACML may make little to no difference to the likelihood of complete cure (RR 1.05, 95% CI 0.90 to 1.23; 7 RCTs, 676 participants; low-certainty evidence). Based on moderate-certainty evidence (3 RCTs, 464 participants), miltefosine probably increases nausea rates (RR 2.45, 95% CI 1.72 to 3.49) and vomiting (RR 4.76, 95% CI 1.82 to 12.46) compared to IMMA. Recurrence risk was not reported. For the rest of the key comparisons, recurrence risk was not reported, and risk of adverse events could not be estimated. Compared to IMMA, at 6 to 12 months FU, oral azithromycin given for 20 to 28 days to treat L. braziliensis infections in ACML probably reduces the likelihood of complete cure (RR 0.51, 95% CI 0.34 to 0.76; 2 RCTs, 93 participants; moderate-certainty evidence). Compared to intravenous MA (IVMA) and placebo, at 12 month FU, adding topical imiquimod to IVMA, given for 20 days to treat L. braziliensis, L. guyanensis and L. peruviana infections in ACL probably makes little to no difference to the likelihood of complete cure (RR 1.30, 95% CI 0.95 to 1.80; 1 RCT, 80 participants; moderate-certainty evidence). Compared to MA, at 6 months FU, one session of local thermotherapy to treat L. panamensis and L. braziliensis infections in ACL reduces the likelihood of complete cure (RR 0.80, 95% CI 0.68 to 0.95; 1 RCT, 292 participants; high-certainty evidence). Compared to IMMA and placebo, at 26 weeks FU, adding oral pentoxifylline to IMMA to treat CL (species not stated) probably makes little to no difference to the likelihood of complete cure (RR 0.86, 95% CI 0.63 to 1.18; 1 RCT, 70 participants; moderate-certainty evidence).
AUTHORS' CONCLUSIONS
Evidence certainty was mostly moderate or low, due to methodological shortcomings, which precluded conclusive results. Overall, both IMMA and oral miltefosine probably result in an increase in cure rates, and nausea and vomiting are probably more common with miltefosine than with IMMA. Future trials should investigate interventions for mucosal leishmaniasis and evaluate recurrence rates of cutaneous leishmaniasis and its progression to mucosal disease.
Topics: Administration, Oral; Adult; Antiprotozoal Agents; Azithromycin; BCG Vaccine; Female; Humans; Hyperthermia, Induced; Immunocompetence; Injections, Intramuscular; Injections, Intravenous; Interferon-gamma; Leishmaniasis Vaccines; Leishmaniasis, Cutaneous; Leishmaniasis, Mucocutaneous; Male; Meglumine Antimoniate; Pentoxifylline; Phosphorylcholine; Randomized Controlled Trials as Topic
PubMed: 32853410
DOI: 10.1002/14651858.CD004834.pub3