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Viruses Mar 2024The post-transcriptional regulatory element (PRE) is present in all HBV mRNAs and plays a major role in their stability, nuclear export, and enhancement of viral gene... (Review)
Review
The post-transcriptional regulatory element (PRE) is present in all HBV mRNAs and plays a major role in their stability, nuclear export, and enhancement of viral gene expression. Understanding PRE's structure, function, and mode of action is essential to leverage its potential as a therapeutic target. A wide range of PRE-based reagents and tools have been developed and assessed in preclinical and clinical settings for therapeutic and biotechnology applications. This manuscript aims to provide a systematic review of the characteristics and mechanism of action of PRE, as well as elucidating its current applications in basic and clinical research. Finally, we discuss the promising opportunities that PRE may provide to antiviral development, viral biology, and potentially beyond.
Topics: Animals; Humans; Antiviral Agents; Gene Expression Regulation, Viral; Hepatitis B; Hepatitis B virus; RNA Processing, Post-Transcriptional; RNA, Messenger; RNA, Viral
PubMed: 38675871
DOI: 10.3390/v16040528 -
Molecules (Basel, Switzerland) Apr 2024Nonalcoholic fatty liver disease (NAFLD) is the liver component of a cluster of conditions, while its subtype, nonalcoholic steatohepatitis (NASH), emerges as a... (Review)
Review
Nonalcoholic fatty liver disease (NAFLD) is the liver component of a cluster of conditions, while its subtype, nonalcoholic steatohepatitis (NASH), emerges as a potentially progressive liver disorder that harbors the risk of evolving into cirrhosis and culminating in hepatocellular carcinoma (HCC). NASH and cardiovascular disease (CVD) have common risk factors, but compared to liver-related causes, the most common cause of death in NASH patients is CVD. Within the pharmacological armamentarium, statins, celebrated for their lipid-modulating prowess, have now garnered attention for their expansive therapeutic potential in NASH. Evidence from a plethora of studies suggests that statins not only manifest anti-inflammatory and antifibrotic properties but also impart a multifaceted beneficial impact on hepatic health. In this review, we used "statin", "NAFLD", "NASH", and "CVD" as the major keywords and conducted a literature search using the PubMed and Web of Science databases to determine the safety and efficacy of statins in patients and animals with NASH and NAFLD, and the mechanism of statin therapy for NASH. Simultaneously, we reviewed the important role of the intestinal microbiota in statin therapy for NASH, as it is hoped that statins will provide new insights into modulating the harmful inflammatory microbiota in the gut and reducing systemic inflammation in NASH patients.
Topics: Non-alcoholic Fatty Liver Disease; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Animals; Gastrointestinal Microbiome; Treatment Outcome; Cardiovascular Diseases
PubMed: 38675679
DOI: 10.3390/molecules29081859 -
International Journal of Molecular... Apr 2024Non-alcoholic fatty liver disease (NAFLD) is the predominant cause of chronic liver conditions, and its progression is marked by evolution to non-alcoholic steatosis,... (Review)
Review
Non-alcoholic fatty liver disease (NAFLD) is the predominant cause of chronic liver conditions, and its progression is marked by evolution to non-alcoholic steatosis, steatohepatitis, cirrhosis related to non-alcoholic steatohepatitis, and the potential occurrence of hepatocellular carcinoma. In our systematic review, we searched two databases, Medline (via Pubmed Central) and Scopus, from inception to 5 February 2024, and included 73 types of research (nine clinical studies and 64 pre-clinical studies) from 2854 published papers. Our extensive research highlights the impact of Berberine on NAFLD pathophysiology mechanisms, such as Adenosine Monophosphate-Activated Protein Kinase (AMPK), gut dysbiosis, peroxisome proliferator-activated receptor (PPAR), Sirtuins, and inflammasome. Studies involving human subjects showed a measurable reduction of liver fat in addition to improved profiles of serum lipids and hepatic enzymes. While current drugs for NAFLD treatment are either scarce or still in development or launch phases, Berberine presents a promising profile. However, improvements in its formulation are necessary to enhance the bioavailability of this natural substance.
Topics: Berberine; Non-alcoholic Fatty Liver Disease; Humans; Animals; Liver Cirrhosis; Liver
PubMed: 38673787
DOI: 10.3390/ijms25084201 -
Biomolecules Mar 2024Cholesterol is an essential molecule of life, and its synthesis can be inhibited by both genetic and nongenetic mechanisms. Hundreds of chemicals that we are exposed to... (Review)
Review
Cholesterol is an essential molecule of life, and its synthesis can be inhibited by both genetic and nongenetic mechanisms. Hundreds of chemicals that we are exposed to in our daily lives can alter sterol biosynthesis. These also encompass various classes of FDA-approved medications, including (but not limited to) commonly used antipsychotic, antidepressant, antifungal, and cardiovascular medications. These medications can interfere with various enzymes of the post-lanosterol biosynthetic pathway, giving rise to complex biochemical changes throughout the body. The consequences of these short- and long-term homeostatic disruptions are mostly unknown. We performed a comprehensive review of the literature and built a catalogue of chemical agents capable of inhibiting post-lanosterol biosynthesis. This process identified significant gaps in existing knowledge, which fall into two main areas: mechanisms by which sterol biosynthesis is altered and consequences that arise from the inhibitions of the different steps in the sterol biosynthesis pathway. The outcome of our review also reinforced that sterol inhibition is an often-overlooked mechanism that can result in adverse consequences and that there is a need to develop new safety guidelines for the use of (novel and already approved) medications with sterol biosynthesis inhibiting side effects, especially during pregnancy.
Topics: Animals; Humans; Biosynthetic Pathways; Cholesterol; Lanosterol; Sterols
PubMed: 38672427
DOI: 10.3390/biom14040410 -
Nutricion Hospitalaria Jun 2024Introduction: early exposure to cadmium toxic metal has been suggested to be associated with reduced infants/children growth; nevertheless, the available evidence is... (Meta-Analysis)
Meta-Analysis
Introduction: early exposure to cadmium toxic metal has been suggested to be associated with reduced infants/children growth; nevertheless, the available evidence is contradictory. Objective: this meta-analysis aimed to examine the association of cadmium exposure through biological samples to growth measurements of infants/children, including body weight, height, body mass index (BMI), BMI-for-age (BMI Z-score), weight-for-age (WAZ), height-for-age (HAZ), and weight-for-height (WHZ) z-scores. Methods: a systematic search in PubMed and Scopus was implemented to obtain the related studies. The standardized beta coefficients (β) and 95 % confidence intervals (95 % CI) were used as effect sizes to test the associations using the random effects analysis. Results: a total of 15 studies with 6,181 participants were included in the meta-analysis. In the overall analysis, pooled analysis of available data revealed that cadmium exposure was inversely linked to height (β = -0.06, 95 % CI = -0.12 to -0.01) and WAZ (β = -0.01, 95 % CI = -0.02 to -0.003). These relationships were also supported by prospective cohort studies and urinary cadmium exposure. In the stratified analysis, cadmium exposure was negatively linked to the weight of children in prospective cohort studies, in studies that assessed urinary cadmium exposure. No significant association was detected between cadmium exposure and BMI, BMI Z-score, WHZ, and HAZ in the overall and subgroup analyses. Conclusions: this meta-analysis emphasized the importance of cadmium exposure as a risk factor for growth failure in infants/children.
Topics: Humans; Cadmium; Child; Infant; Child, Preschool; Growth Disorders; Metals, Heavy; Body Mass Index; Body Height; Body Weight
PubMed: 38666332
DOI: 10.20960/nh.04965 -
Endocrinology, Diabetes & Metabolism May 2024The once-weekly insulin icodec, a new basal insulin analog, may positively support a reduction in injection frequency and improve adherence to therapy in type 2 diabetes... (Comparative Study)
Comparative Study Meta-Analysis
Clinical Outcomes With Once-Weekly Insulin Icodec Versus Once-Daily Insulin Glargine U100 in Insulin-Naïve and Previously Insulin-Treated Individuals With Type 2 Diabetes: A Meta-Analysis of Randomised Controlled Trials.
AIMS
The once-weekly insulin icodec, a new basal insulin analog, may positively support a reduction in injection frequency and improve adherence to therapy in type 2 diabetes (T2D). This study aimed to evaluate the safety and efficacy of insulin icodec compared with those of once-daily glargine U100.
METHODS
A comprehensive literature search was conducted using PubMed/MEDLINE, Embase and the Cochrane Library from inception till September 2023. Data about clinical outcomes in both groups were extracted. Forest plots were generated using the random-effects model by pooling odds ratios (ORs) and mean differences (MDs).
RESULTS
Five randomised controlled trials and 2019 individuals with T2DM were included. In the pooled analysis, time in range was significantly higher (MD = 4.35; 95% CI: 1.65 to 7.05; p = 0.002) in the icodec group than in the once-daily glargine group. The HbA1c levels were significantly reduced (MD = -0.13; 95% CI: -0.24 to -0.03; p = 0.02) in the weekly icodec group compared with those in the once-daily glargine group. The weight gain was significantly less in the glargine group than in the weekly icodec group (MD = 0.41; 95% CI: 0.04 to 0.78; p = 0.03); however, in the subgroup analysis, this change became statistically insignificant in both insulin-naïve and previously insulin-treated individuals. The results were comparable across two groups for fasting plasma glucose levels, hypoglycaemia alert (Level 1), clinically significant (Level 2) or severe hypoglycaemia (Level 3), and adverse events.
CONCLUSION
Insulin icodec was associated with a reduction in glycated haemoglobin levels and higher time in range, with a similar safety profile as compared to insulin glargine U100. However, further evidence is still needed to reach a definitive conclusion.
Topics: Humans; Blood Glucose; Diabetes Mellitus, Type 2; Drug Administration Schedule; Glycated Hemoglobin; Hypoglycemic Agents; Insulin; Insulin Glargine; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 38659132
DOI: 10.1002/edm2.480 -
BMC Endocrine Disorders Apr 2024Sodium glucose cotransporter 2 (SGLT2) inhibitors are widely used in type 2 diabetes mellitus (T2DM) therapy. The impact of SGLT2 inhibitors on bone metabolism has been... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Sodium glucose cotransporter 2 (SGLT2) inhibitors are widely used in type 2 diabetes mellitus (T2DM) therapy. The impact of SGLT2 inhibitors on bone metabolism has been widely taken into consideration. But there are controversial results in the study on the effect of SGLT2 inhibitors on bone metabolism in patients with T2DM. Therefore, we aimed to examine whether and to what extent SGLT2 inhibitors affect bone metabolism in patients with T2DM.
METHODS
A literature search of randomized controlled trials (RCTs) was conducted through PubMed, Web of Science, Embase, Cochrane databases, and Scopus from inception until 15 April 2023. Eligible RCTs compared the effects of SGLT2 inhibitors versus placebo on bone mineral density and bone metabolism in patients with T2DM. To evaluate the differences between groups, a meta-analysis was conducted using the random effects inverse-variance model by utilizing standardized mean differences (SMD).
RESULTS
Through screening, 25 articles were finally included, covering 22,828 patients. The results showed that, compared with placebo, SGLT2 inhibitors significantly increased parathyroid hormone (PTH, SMD = 0.13; 95%CI: 0.06, 0.20), and cross-linked C-terminal telopeptides of type I collagen (CTX, SMD = 0.11; 95%CI: 0.01, 0.21) in patients with T2DM, decreased serum alkaline phosphatase levels (ALP, SMD = -0.06; 95%CI: -0.10, -0.03), and had no significant effect on bone mineral density (BMD), procollagen type 1 N-terminal propeptide (P1NP), 25-hydroxy vitamin D, tartrate resistant acid phosphatase-5b (TRACP-5b) and osteocalcin.
CONCLUSIONS
SGLT2 inhibitors may negatively affect bone metabolism by increasing serum PTH, CTX, and decreasing serum ALP. This conclusion needs to be verified by more studies due to the limited number and quality of included studies.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO, identifier CRD42023410701.
Topics: Humans; Sodium-Glucose Transporter 2 Inhibitors; Diabetes Mellitus, Type 2; Bone Density; Bone and Bones; Randomized Controlled Trials as Topic
PubMed: 38658986
DOI: 10.1186/s12902-024-01575-8 -
Renal Failure Dec 2024Shenkang injection (SKI) has been widely used in China for many years for the treatment of kidney disease. The objective of this systematic review was to assess the... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Shenkang injection (SKI) has been widely used in China for many years for the treatment of kidney disease. The objective of this systematic review was to assess the efficacy of Shenkang injection for the treatment of acute kidney injury (AKI).
METHODS
A search was conducted across seven databases, encompassing data from the inception of each database through October 8, 2023. Randomized controlled trials comparing SKI-treated AKI patients with control subjects were extracted. The main outcome measure was serum creatinine (SCr) levels. Secondary outcomes included blood urea nitrogen (BUN), serum cystatin C (CysC), 24-h urine protein (24 h-Upro) levels, APACHE II score and adverse reactions.
RESULTS
This meta-analysis included eleven studies, and the analysis indicated that, compared with the control group, SKI significantly decreased SCr [WMD = -23.31, 95% CI (-28.06, -18.57); < 0.001]; BUN [WMD = -2.07, 95% CI (-2.56, -1.57); < 0.001]; CysC [WMD = -0.55, 95% CI (-0.78, -0.32), < 0.001]; 24-h urine protein [WMD = -0.43, 95% CI (-0.53, -0.34), < 0.001]; and the APACHE II score [WMD = -3.07, 95% CI (-3.67, -2.48), < 0.001]. There was no difference in adverse reactions between the SKI group and the control group [RR = 1.32, 95% CI (0.66, 2.63), = 0.431].
CONCLUSION
The use of SKI in AKI patients may reduce SCr, BUN, CysC, 24-h Upro levels, and APACHE II scores in AKI patients. The incidence of adverse reactions did not differ from that in the control group. Additional rigorous clinical trials will be necessary in the future to thoroughly evaluate and establish the effectiveness of SKI in the treatment of AKI.
Topics: Humans; Acute Kidney Injury; APACHE; Blood Urea Nitrogen; Creatinine; Cystatin C; Drugs, Chinese Herbal; Injections; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 38655870
DOI: 10.1080/0886022X.2024.2338566 -
Public Health Nutrition Apr 2024Several meta-analyses have suggested the beneficial effect of vitamin D on patients infected with severe acute respiratory syndrome coronavirus-2. This umbrella... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
Several meta-analyses have suggested the beneficial effect of vitamin D on patients infected with severe acute respiratory syndrome coronavirus-2. This umbrella meta-analysis aims to evaluate influence of vitamin D supplementation on clinical outcomes and the mortality rate of COVID-19 patients.
DESIGN
Present study was designed as an umbrella meta-analysis. The following international databases were systematically searched till March 2023: Web of Science, PubMed, Scopus, and Embase.
SETTINGS
Random-effects model was employed to perform meta-analysis. Using AMSTAR critical evaluation tools, the methodological quality of the included meta-analyses was evaluated.
PARTICIPANTS
Adult patients suffering from COVID-19 were studied.
RESULTS
Overall, 13 meta-analyses summarising data from 4 randomised controlled trial and 9 observational studies were identified in this umbrella review. Our findings revealed that vitamin D supplementation and status significantly reduced mortality of COVID-19 [Interventional studies: (ES = 0·42; 95 % CI: 0·10, 0·75, < 0·001; = 20·4 %, = 0·285) and observational studies (ES = 1·99; 95 % CI: 1·37, 2·62, < 0·001; = 00·0 %, = 0·944). Also, vitamin D deficiency increased the risk of infection and disease severity among patients.
CONCLUSION
Overall, vitamin D status is a critical factor influencing the mortality rate, disease severity, admission to intensive care unit and being detached from mechanical ventilation. It is vital to monitor the vitamin D status in all patients with critical conditions including COVID patients.
Topics: Adult; Humans; COVID-19; COVID-19 Drug Treatment; Critical Care; Dietary Supplements; Intensive Care Units; Observational Studies as Topic; Randomized Controlled Trials as Topic; SARS-CoV-2; Vitamin D; Vitamin D Deficiency; Vitamins
PubMed: 38654693
DOI: 10.1017/S1368980024000934 -
Nutrition & Diabetes Apr 2024The beneficial effects of folate have been observed under different conditions, but the available evidence on inflammation and reduction of cardiovascular disease (CVD)... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The beneficial effects of folate have been observed under different conditions, but the available evidence on inflammation and reduction of cardiovascular disease (CVD) in type 2 diabetes mellitus (T2DM) is limited. The study aimed to explore the effects of folate on inflammation and homocysteine amongst individuals with T2DM.
METHODS
PubMed, Scopus, and Cochrane Library were used to search for evidence. A random-effect model meta-analysis through Review Manager (version 5.4) and metaHun was performed. Results were reported as standardized mean differences (SMD) and 95% confidence intervals graphically using forest and funnel plots.
RESULTS
Data from 9 trials with 426 patients living with T2DM were analyzed. Folic acid supplementation significantly revealed a large effect size on homocysteine levels compared to placebo, SMD = -1.53, 95%CI (-2.14,-0.93), p < 0.05. Additionally, we observed a medium marginal effect size on C-reactive protein (SMD = -0.68, 95%CI (-1.34, -0.01), p = 0.05). However, no significant effect on tumor necrosis factor-α (SMD = -0.86, 95%CI (-2.65, 0.93), p = 0.34), and interleukin-6 (SMD = -0.04, 95%CI (-1.08, 1.01), p = 0.95) was observed.
CONCLUSION
Evidence analyzed in this study suggests that folic acid supplementation in T2DM reduces homocysteine and may mitigate CVDs. However, its effect on inflammation is inconclusive.
Topics: Humans; C-Reactive Protein; Diabetes Mellitus, Type 2; Dietary Supplements; Folic Acid; Homocysteine; Inflammation; Interleukin-6; Randomized Controlled Trials as Topic; Tumor Necrosis Factor-alpha
PubMed: 38649347
DOI: 10.1038/s41387-024-00282-6