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Journal of Pharmacy & Pharmaceutical... 2015We developed an experimental model of ethanol-induced dermatotoxicity and hepatocytoxicity using normal human keratinocytes and normal human hepatocytes that preserve... (Review)
Review
BACKGROUND
We developed an experimental model of ethanol-induced dermatotoxicity and hepatocytoxicity using normal human keratinocytes and normal human hepatocytes that preserve inducible cytochrome p450 activities. The original work was described in several articles. The objective of this study was to determine whether hyaluronic acid attenuates skin necrosis, and to further clarify its uses in wound repair in humans, animal models and in vitro studies.
METHODS
We performed a systematic review of the literature using the terms "hyaluronic acid" and "wound healing". PubMed was searched for studies published during the period 2010-2014.
RESULTS
Hyaluronic acid is used in tissue regeneration alone or in combination with herbal or Western medicine. Scaffolds made up of hyaluronic acid were used to embed basic fibroblast growth factor.
CONCLUSION
Hyaluronic acid extracts are safe and efficacious products to be used in skin repair.
Topics: Animals; Fibroblast Growth Factor 2; Hepatocytes; Humans; Hyaluronic Acid; Keratinocytes; Skin; Wound Healing
PubMed: 25877441
DOI: 10.18433/j3k89d -
Advances in Therapy Apr 2020Silymarin, an extract from milk thistle seeds, has been used for centuries to treat hepatic conditions. Preclinical data indicate that silymarin can reduce oxidative...
Silymarin, an extract from milk thistle seeds, has been used for centuries to treat hepatic conditions. Preclinical data indicate that silymarin can reduce oxidative stress and consequent cytotoxicity, thereby protecting intact liver cells or cells not yet irreversibly damaged. Eurosil 85 is a proprietary formulation developed to maximize the oral bioavailability of silymarin. Most of the clinical research on silymarin has used this formulation. Silymarin acts as a free radical scavenger and modulates enzymes associated with the development of cellular damage, fibrosis and cirrhosis. These hepatoprotective effects were observed in clinical studies in patients with alcoholic or non-alcoholic fatty liver disease, including patients with cirrhosis. In a pooled analysis of trials in patients with cirrhosis, silymarin treatment was associated with a significant reduction in liver-related deaths. Moreover, in patients with diabetes and alcoholic cirrhosis, silymarin was also able to improve glycemic parameters. Patients with drug-induced liver injuries were also successfully treated with silymarin. Silymarin is generally very well tolerated, with a low incidence of adverse events and no treatment-related serious adverse events or deaths reported in clinical trials. For maximum benefit, treatment with silymarin should be initiated as early as possible in patients with fatty liver disease and other distinct liver disease manifestations such as acute liver failure, when the regenerative potential of the liver is still high and when removal of oxidative stress, the cause of cytotoxicity, can achieve the best results.
Topics: Blood Glucose; Diabetes Mellitus; Hepatocytes; Humans; Liver Cirrhosis; Liver Diseases; Liver Diseases, Alcoholic; Non-alcoholic Fatty Liver Disease; Protective Agents; Silymarin
PubMed: 32065376
DOI: 10.1007/s12325-020-01251-y -
Clinical Gastroenterology and... Apr 2022Intestinal strictures are a common complication of Crohn's disease (CD). Biomarkers of intestinal strictures would assist in their prediction, diagnosis, and monitoring....
BACKGROUND AND AIMS
Intestinal strictures are a common complication of Crohn's disease (CD). Biomarkers of intestinal strictures would assist in their prediction, diagnosis, and monitoring. Herein we provide a comprehensive systematic review of studies assessing biomarkers that may predict or diagnose CD-associated strictures.
METHODS
We performed a systematic review of PubMed, EMBASE, ISI Web of Science, Cochrane Library, and Scopus to identify citations pertaining to biomarkers of intestinal fibrosis through July 6, 2020, that used a reference standard of full-thickness histopathology or cross-sectional imaging or endoscopy. Studies were categorized based on the type of biomarker they evaluated (serum, genetic, histopathologic, or fecal).
RESULTS
Thirty-five distinct biomarkers from 3 major groups were identified: serum (20 markers), genetic (9 markers), and histopathology (6 markers). Promising markers include cartilage oligomeric matrix protein, hepatocyte growth factor activator, and lower levels of microRNA-19-3p (area under the curves were 0.805, 0.738, and 0.67, respectively), and multiple anti-flagellin antibodies (A4-Fla2 [odds ratio, 3.41], anti Fla-X [odds ratio, 2.95], and anti-CBir1 [multiple]). Substantial heterogeneity was observed and none of the markers had undergone formal validation. Specific limitations to acceptance of these markers included failure to use a standardized definition of stricturing disease, lack of specificity, and insufficient relevance to the pathogenesis of intestinal strictures or incomplete knowledge regarding their operating properties.
CONCLUSIONS
There is a lack of well-defined studies on biomarkers of intestinal stricture. Development of reliable and accurate biomarkers of stricture is a research priority. Biomarkers can support the clinical management of CD patients and aid in the stratification and monitoring of patients during clinical trials of future antifibrotic drug candidates.
Topics: Biomarkers; Cartilage Oligomeric Matrix Protein; Constriction, Pathologic; Crohn Disease; Humans; Intestinal Obstruction; MicroRNAs; Serine Endopeptidases
PubMed: 34089850
DOI: 10.1016/j.cgh.2021.05.054 -
Cureus Sep 2022In recent times, nonalcoholic fatty liver disease (NAFLD) has been considered one of the major causes of liver disease across the world. NAFLD is defined as the... (Review)
Review
In recent times, nonalcoholic fatty liver disease (NAFLD) has been considered one of the major causes of liver disease across the world. NAFLD is defined as the deposition of triglycerides in the liver and is associated with obesity and metabolic syndrome. Hyperinsulinemia, insulin resistance (IR), fatty liver, hepatocyte injury, unbalanced proinflammatory cytokines, mitochondrial dysfunction, oxidative stress, liver inflammation, and fibrosis are the main pathogenesis in NAFLD. Recent studies suggest that the action of intestinal microbiota through chronic inflammation, increased intestinal permeability, and energy uptake plays a vital role in NAFLD. Moreover, polycystic ovarian syndrome also causes NAFLD development through IR. Age, gender, race, ethnicity, sleep, diet, sedentary lifestyle, and genetic and epigenetic pathways are some contributing factors of NAFLD that can exacerbate the risk of liver cirrhosis and hepatocellular carcinoma (HCC) and eventually lead to death. NAFLD has various presentations, including fatigue, unexplained weight loss, bloating, upper abdominal pain, decreased appetite, headache, anxiety, poor sleep, increased thirst, palpitation, and a feeling of warmth. Some studies have shown that NAFLD with severe coronavirus disease 2019 (COVID-19) has poor outcomes. The gold standard for NAFLD diagnosis is liver biopsy. Other diagnostic tools are imaging tests, serum biomarkers, microbiota markers, and tests for extrahepatic complications. There are no specific treatments for NAFLD. Therefore, the main concern for NAFLD is treating the comorbid conditions such as anti-diabetic agents for type 2 diabetes mellitus, statins to reduce HCC progression, antioxidants to prevent hepatocellular damage, and bariatric surgery for patients with a BMI of >40 kg/m and >35 kg/m with comorbidities. Lifestyle and dietary changes are considered preventive strategies against NAFLD advancement. Inadequate treatment of NAFLD further leads to cardiac consequences, sleep apnea, chronic kidney disease, and inflammatory bowel disease. In this systematic review, we have briefly discussed the risk factors, pathogenesis, clinical features, and numerous consequences of NAFLD. We have also reviewed various guidelines for NAFLD diagnosis along with existing therapeutic strategies for the management and prevention of the disease.
PubMed: 36320966
DOI: 10.7759/cureus.29657 -
Antioxidants (Basel, Switzerland) Jul 2023Ethanol consumption triggers oxidative stress by generating reactive oxygen species (ROS) through its metabolites. This process leads to steatosis and liver... (Review)
Review
Ethanol consumption triggers oxidative stress by generating reactive oxygen species (ROS) through its metabolites. This process leads to steatosis and liver inflammation, which are critical for the development of alcoholic liver disease (ALD). Autophagy is a regulated dynamic process that sequesters damaged and excess cytoplasmic organelles for lysosomal degradation and may counteract the harmful effects of ROS-induced oxidative stress. These effects include hepatotoxicity, mitochondrial damage, steatosis, endoplasmic reticulum stress, inflammation, and iron overload. In liver diseases, particularly ALD, macroautophagy has been implicated as a protective mechanism in hepatocytes, although it does not appear to play the same role in stellate cells. Beyond the liver, autophagy may also mitigate the harmful effects of alcohol on other organs, thereby providing an additional layer of protection against ALD. This protective potential is further supported by studies showing that drugs that interact with autophagy, such as rapamycin, can prevent ALD development in animal models. This systematic review presents a comprehensive analysis of the literature, focusing on the role of autophagy in oxidative stress regulation, its involvement in organ-organ crosstalk relevant to ALD, and the potential of autophagy-targeting therapeutic strategies.
PubMed: 37507963
DOI: 10.3390/antiox12071425 -
The Cochrane Database of Systematic... Oct 2018Peripheral arterial disease (PAD), caused by narrowing of the arteries in the limbs, is increasing in incidence and prevalence as our population is ageing and as... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Peripheral arterial disease (PAD), caused by narrowing of the arteries in the limbs, is increasing in incidence and prevalence as our population is ageing and as diabetes is becoming more prevalent. PAD can cause pain in the limbs while walking, known as intermittent claudication, or can be more severe and cause pain while at rest, ulceration, and ultimately gangrene and limb loss. This more severe stage of PAD is known as 'critical limb ischaemia'. Treatments for PAD include medications that help to reduce the increased risk of cardiovascular events and help improve blood flow, as well as endovascular or surgical repair or bypass of the blocked arteries. However, many people are unresponsive to medications and are not suited to surgical or endovascular treatment, leaving amputation as the last option. Gene therapy is a novel approach in which genetic material encoding for proteins that may help increase revascularisation is injected into the affected limbs of patients. This type of treatment has been shown to be safe, but its efficacy, especially regarding ulcer healing, effects on quality of life, and other symptomatic outcomes remain unknown.
OBJECTIVES
To assess the effects of gene therapy for symptomatic peripheral arterial disease.
SEARCH METHODS
The Cochrane Vascular Information Specialist searched Cochrane CENTRAL, the Cochrane Vascular Specialised Register, MEDLINE Ovid, Embase Ovid, CINAHL, and AMED, along with trials registries (all searched 27 November 2017). We also checked reference lists of included studies and systematic reviews for further studies.
SELECTION CRITERIA
We included randomised and quasi-randomised studies that evaluated gene therapy versus no gene therapy in people with PAD. We excluded studies that evaluated direct growth hormone treatment or cell-based treatments.
DATA COLLECTION AND ANALYSIS
Two review authors independently selected studies, performed quality assessment, and extracted data from the included studies. We collected pertinent information on each study, as well as data for the outcomes of amputation-free survival, ulcer healing, quality of life, amputation, all-cause mortality, ankle brachial index, symptom scores, and claudication distance.
MAIN RESULTS
We included in this review a total of 17 studies with 1988 participants (evidence current until November 2017). Three studies limited their inclusion to people with intermittent claudication, 12 limited inclusion to people with varying levels of critical limb ischaemia, and two included people with either condition. Study investigators evaluated many different types of gene therapies, using different protocols. Most studies evaluated growth factor-encoding gene therapy, with six studies using vascular endothelial growth factor (VEGF)-encoding genes, four using hepatocyte growth factor (HGF)-encoding genes, and three using fibroblast growth factor (FGF)-encoded genes. Two studies evaluated hypoxia-inducible factor 1-alpha (HIF-1α) gene therapy, one study used a developmental endothelial locus-1 gene therapy, and the final study evaluated a stromal cell-derived factor-1 (SDF-1) gene therapy. Most studies reported outcomes after 12 months of follow-up, but follow-up ranged from three months to two years.Overall risk of bias varied between studies, with many studies not providing sufficient detail for adequate determination of low risk of bias for many domains. Two studies did not utilise a placebo control, leading to risk of performance bias. Several studies reported in previous protocols or in their Methods sections that they would report on certain outcomes for which no data were then reported, increasing risk of reporting bias. All included studies reported sponsorships from corporate entities that led to unclear risk of other bias. The overall quality of evidence ranged from moderate to very low, generally as the result of heterogeneity and imprecision, with few or no studies reporting on outcomes.Evidence suggests no clear differences for the outcomes of amputation-free survival, major amputation, and all-cause mortality between those treated with gene therapy and those not receiving this treatment (all moderate-quality evidence). Low-quality evidence suggests improvement in complete ulcer healing with gene therapy (odds ratio (OR) 2.16, 95% confidence interval (CI) 1.02 to 4.59; P = 0.04). We could not combine data on quality of life and can draw no conclusions at this time regarding this outcome (very low-quality evidence). We included one study in the meta-analysis for ankle brachial index, which showed no clear differences between treatments, but we can draw no overall association (low-quality evidence). We combined in a meta-analysis pain symptom scores as assessed by visual analogue scales from two studies and found no clear differences between treatment groups (very low-quality evidence). We carried out extensive subgroup analyses by PAD classification, dosage schedule, vector type, and gene used but identified no substantial differences.
AUTHORS' CONCLUSIONS
Moderate-quality evidence shows no clear differences in amputation-free survival, major amputation, and all-cause mortality between those treated with gene therapy and those not receiving gene therapy. Some evidence suggests that gene therapy may lead to improved complete ulcer healing, but this outcome needs to be explored with improved reporting of the measure, such as decreased ulcer area in cm², and better description of ulcer types and healing. Further standardised data that are amenable to meta-analysis are needed to evaluate other outcomes such as quality of life, ankle brachial index, symptom scores, and claudication distance.
Topics: Amputation, Surgical; Chemokine CXCL12; Extremities; Fibroblast Growth Factors; Genetic Therapy; Hepatocyte Growth Factor; Humans; Hypoxia-Inducible Factor 1, alpha Subunit; Intermittent Claudication; Ischemia; Peripheral Arterial Disease; Randomized Controlled Trials as Topic; Vascular Endothelial Growth Factor A
PubMed: 30380135
DOI: 10.1002/14651858.CD012058.pub2 -
Cureus Apr 2022The incidence of liver disease increases throughout the years due to many lifestyle factors; thus, the only definite treatment available for chronic liver disease is a... (Review)
Review
The incidence of liver disease increases throughout the years due to many lifestyle factors; thus, the only definite treatment available for chronic liver disease is a liver transplant. However, the liver has a natural ability to repair itself and regenerate its hepatic tissue from stem cells. It is hypothesized that by inducing the liver with specific growth factors and cytokines such as interleukin 6 (IL-6) compared to general growth factors like growth differentiation factor 15 (GDF-15), it can regenerate, decreasing the need for liver transplant procedures. MEDLINE, the Journal of Hepatology, and Google Scholar were used to find articles. Various studies, including epidemiological studies dated from the year 2000 and greater, were used for the introduction. The results used only randomized control trials, experimental studies, and primary articles published since 2000. This compared the results of manipulating variables to determine the effects of hepatic regeneration by either specific hepatocyte growth factors or general growth factors like GDF-15. A total of 10 collected studies showed increased levels of gene expression and function, improved gross morphology, and histological appearance of the liver when induced by cytokines and specific growth factors versus general growth factors. Overall, the hypothesis was proven. The effects of GDF-15 were not significant compared to the effects of hepatocyte-specific growth factors and cytokines like IL-6 because they have two different effects on the liver after liver injury. Future studies should investigate this topic on the human hepatic regenerative ability, plus compare the effects of general growth factors like GDF-15 and specific hepatocyte growth factors and cytokines such as IL-6 in human liver tissue.
PubMed: 35651436
DOI: 10.7759/cureus.24539 -
International Journal of Preventive... 2022Neonatal jaundice is a prevalent disease that causes many complications, including kernicterus and even death. Previous studies have shown that clofibrate as an aryloxy... (Review)
Review
BACKGROUND
Neonatal jaundice is a prevalent disease that causes many complications, including kernicterus and even death. Previous studies have shown that clofibrate as an aryloxy isobutyric acid derivate can be effectively applied for the treatment of neonatal jaundice. Thus, this review was carried out to investigate the effects and mechanism of action of clofibrate on neonatal jaundice.
METHODS
The keywords such as "Clofibrate" in combination with "Neonatal jaundice" or "Neonatal hyperbilirubinemia" or "Newborn Jaundice" were used to search for relevant publications indexed in the Institute for Scientific Information (ISI), Scopus, PubMed, and Google Scholar databases. Finally, after reviewing the studies, 24 papers were included in this study.
RESULTS
Results showed that the processes of albumin-bound bilirubin transfer to the hepatocytes, hepatic uptake, and storage via ligandin, hepatic conjugation via uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1), conjugation into the bile via MRP2 represent the main action mechanism of clofibrate that turns it into the bilirubin conjugates and expels it from the bile. Besides, clofibrate has been shown to reduce the level of Total Serum Bilirubin (TSB) in infants even at a dosage of 25 mg/kg without leaving side effects.
CONCLUSIONS
The results of this review revealed that clofibrate effectively reduces TSB in short-term usage and can even have a promising effect at the dosage of 25 mg/kg in full-term infants. Most studies have shown this property over a short period in term infants, and there is no evidence about long-term usage in this regard.
PubMed: 35281975
DOI: 10.4103/ijpvm.IJPVM_407_20 -
Cureus Mar 2023Statins are the most widely used drugs for reducing lipid and cholesterol levels in the blood. However, statins have shown some adverse effects and less acceptance among... (Review)
Review
Statins are the most widely used drugs for reducing lipid and cholesterol levels in the blood. However, statins have shown some adverse effects and less acceptance among patients; hence, new drugs have been promoted in the market. Furthermore, gemcabenes were discovered in 1995 and are now in phase II and III clinical trials. Gemcabene acts by inhibiting incorporation of 14C-acetate into hepatocytes and stops the mechanism of fatty acids and cholesterol synthesis. In this review the six randomized controlled trials (RCTs) were scrutinized from the two databases by using keywords "Gemcabene" AND "Randomized Controlled Trial." The trials were mainly on animal models, and two studies were found to be associated with human subjects. The study concluded that gemcabene was effective as an anti-inflammatory agent and reduced lipid levels and the progression of fibrosis. Hence, further controlled trials are needed to determine its efficacy and safety in human subjects, along with the identification of adverse effects.
PubMed: 37123792
DOI: 10.7759/cureus.36811 -
Biomedicine & Pharmacotherapy =... Jun 2021Thiazole and oxazole are compounds with a heterocyclic nucleus that have attracted the attention of medicinal chemistry due to the great variety of biological activities... (Review)
Review
Thiazole and oxazole are compounds with a heterocyclic nucleus that have attracted the attention of medicinal chemistry due to the great variety of biological activities that they enable. In recent years, their study has increased, finding a wide range of biological activities, including antifungal, antiparasitic, anti-inflammatory, and anticancer activities. This systematic review provides evidence from the literature on the antiproliferative and antitumor activities of thiazole and oxazole and their derivatives from 2014 to April 2020. Three bibliographical databases were consulted (PubMed, Web of Science, and Scopus), and a total of 32 studies were included in this paper based on our eligibility criteria. The analysis of the activity-structure relationship allows us to conclude that most of the promising compounds identified contained thiazole nuclei or derivatives.
Topics: A549 Cells; Animals; Anti-Infective Agents; Anti-Inflammatory Agents; Antifungal Agents; Cell Proliferation; HeLa Cells; Hep G2 Cells; Humans; Oxazoles; Structure-Activity Relationship; Thiazoles
PubMed: 33765586
DOI: 10.1016/j.biopha.2021.111495