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Pharmacology & Therapeutics Jan 2024The treatment of interstitial lung diseases, including idiopathic pulmonary fibrosis (IPF), remains challenging as current available antifibrotic agents are not... (Review)
Review
The treatment of interstitial lung diseases, including idiopathic pulmonary fibrosis (IPF), remains challenging as current available antifibrotic agents are not effective in halting disease progression. Connective tissue growth factor (CTGF), also known as cellular communication factor 2 (CCN2), is a member of the CCN family of proteins that regulates cell signaling through cell surface receptors such as integrins, the activity of cytokines/growth factors, and the turnover of extracellular matrix (ECM) proteins. Accumulating evidence indicates that CTGF plays a crucial role in promoting lung fibrosis through multiple processes, including inducing transdifferentiation of fibroblasts to myofibroblasts, epithelial-mesenchymal transition (EMT), and cooperating with other fibrotic mediators such as TGF-β. Increased expression of CTGF has been observed in fibrotic lungs and inhibiting CTGF signaling has been shown to suppress lung fibrosis in several animal models. Thus, the CTGF signaling pathway is emerging as a potential therapeutic target in IPF and other pulmonary fibrotic conditions. This review provides a comprehensive overview of the current evidence on the pathogenic role of CTGF in pulmonary fibrosis and discusses the current therapeutic agents targeting CTGF using a systematic review approach.
Topics: Animals; Connective Tissue Growth Factor; Fibrosis; Fibroblasts; Transforming Growth Factor beta; Idiopathic Pulmonary Fibrosis; Transforming Growth Factor beta1; Lung
PubMed: 38103794
DOI: 10.1016/j.pharmthera.2023.108578 -
Nutrients Jan 2024Epicatechin is a polyphenol compound that promotes skeletal muscle differentiation and counteracts the pathways that participate in the degradation of proteins. Several... (Review)
Review
Epicatechin is a polyphenol compound that promotes skeletal muscle differentiation and counteracts the pathways that participate in the degradation of proteins. Several studies present contradictory results of treatment protocols and therapeutic effects. Therefore, the objective of this systematic review was to investigate the current literature showing the molecular mechanism and clinical protocol of epicatechin in muscle atrophy in humans, animals, and myoblast cell-line. The search was conducted in Embase, PubMed/MEDLINE, Cochrane Library, and Web of Science. The qualitative analysis demonstrated that there is a commonness of epicatechin inhibitory action in myostatin expression and atrogenes MAFbx, FOXO, and MuRF1. Epicatechin showed positive effects on follistatin and on the stimulation of factors related to the myogenic actions (MyoD, Myf5, and myogenin). Furthermore, the literature also showed that epicatechin can interfere with mitochondrias' biosynthesis in muscle fibers, stimulation of the signaling pathways of AKT/mTOR protein production, and amelioration of skeletal musculature performance, particularly when combined with physical exercise. Epicatechin can, for these reasons, exhibit clinical applicability due to the beneficial results under conditions that negatively affect the skeletal musculature. However, there is no protocol standardization or enough clinical evidence to draw more specific conclusions on its therapeutic implementation.
Topics: Animals; Humans; Catechin; Muscle Fibers, Skeletal; Muscle, Skeletal; Muscular Atrophy; MyoD Protein; TOR Serine-Threonine Kinases
PubMed: 38276564
DOI: 10.3390/nu16020326 -
Biochemical Pharmacology Dec 2023Adiponectin replacement therapy holds the potential to benefit numerous human diseases, and ongoing research applies particular interest in how adiponectin acts against... (Review)
Review
Adiponectin replacement therapy holds the potential to benefit numerous human diseases, and ongoing research applies particular interest in how adiponectin acts against Metabolic-associated Fatty Liver Disease (MAFLD) and Nonalcoholic Steatohepatitis (NASH). However, the pharmacological limitations of the intact protein have prompted a focus on alternative options, specifically peptidic and small molecule agonists targeting the adiponectin receptor. AdipoRon is an extensively researched non-peptidic drug candidate in adiponectin replacement therapy. In turn, ADP355 is an adiponectin-based active short peptide. They have garnered significant attention due to their potential as substitutes for adiponectin. Researchers have studied AdipoRon's and ADP355's efficacy and therapeutic applications in various disease conditions. However, the effects of AdipoRon and ADP355 against NAFLD and NASH models advanced more, and no systematic review explored this area before. This systematic review was conceived to address the deficiency mentioned above and consider the lack of clinical evidence. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were utilized. To assess the risk of bias in systematic review, The Joanna Briggs Institute (JBI) Critical Appraisal Checklist was employed. Results from pre-clinical evidence show that AdipoRon and ADP355 represent promising effects in NAFLD and NASH-related models, including reducing hepatic steatosis, modulating inflammation, improving insulin sensitivity, enhancing mitochondrial function, and protecting against liver fibrosis. While AdipoRon and ADP355 exhibit promise in pre-clinical studies and experimental models, additional clinical trials are necessary to assess their effectiveness, safety, and potential translational therapeutic potential uses in NAFLD and NASH human cases.
Topics: Humans; Non-alcoholic Fatty Liver Disease; Receptors, Adiponectin; Adiponectin
PubMed: 37866803
DOI: 10.1016/j.bcp.2023.115871 -
Advances in Clinical and Experimental... May 2024Atherosclerosis is a complex process involving endothelial dysfunction, vascular inflammation, vascular smooth muscle cell (VSMC) proliferation, angiogenesis, and... (Review)
Review
Atherosclerosis is a complex process involving endothelial dysfunction, vascular inflammation, vascular smooth muscle cell (VSMC) proliferation, angiogenesis, and calcification. One of the pathomechanisms of atherosclerosis is the upregulation of Wnt signaling. This study aimed to summarize the current knowledge regarding the role of Wnt signaling and sclerostin in atherosclerosis, vascular calcification, aneurysms, and mortality based on the PubMed database. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) recommendation and identified 160 papers that were included in this systematic review. The published data highlight that the upregulation of Wnt components facilitates the initiation and progression of atherosclerosis, arterial remodeling, VSMCs proliferation and phenotypic transition to the osteoblastic lineage in the arterial wall. This results in protein secretion, cell migration, calcification, fibrosis and aneurysm formation. The transformation of VSMCs into osteoblast-like cells that is observed in atherosclerosis results in sclerostin expression inhibiting the Wnt pathway. Furthermore, it was shown that sclerostin, expressed in atherosclerotic plaques, inhibits aneurysm formation in a mouse model. However, in humans, while the antisclerostin antibody romosozumab inhibits bone resorption, biochemical parameters of endothelial activation and inflammation are not affected, and the incidence of aneurysms is not increased. It was suggested that detecting sclerostin in the calcified aortic atherosclerotic plaques reflects a defense mechanism against Wnt activation and inhibition of atherosclerosis, although this has only been shown in animal models. Moreover, an increased number of vascular cells converted to osteogenic phenotypes results in increased plasma sclerostin concentrations. Therefore, plasma sclerostin derived from bone limits its importance as a global marker of vascular calcification.
Topics: Humans; Vascular Calcification; Atherosclerosis; Animals; Wnt Signaling Pathway; Adaptor Proteins, Signal Transducing; Genetic Markers
PubMed: 37676098
DOI: 10.17219/acem/169567 -
Obesity Reviews : An Official Journal... Aug 2023Midlife obesity and late-life weight loss confer a greater risk for developing dementia and Alzheimer's disease (AD), but the exact mechanisms behind this phenomenon are... (Meta-Analysis)
Meta-Analysis Review
Midlife obesity and late-life weight loss confer a greater risk for developing dementia and Alzheimer's disease (AD), but the exact mechanisms behind this phenomenon are currently unknown. The answer could lie on the involvement of gastrointestinal factors, such as adipokines (e.g., leptin, adiponectin, and resistin) and ghrelin. In this context, we conducted a pre-registered systematic review and meta-analysis of 42 cross-sectional and 13 longitudinal studies targeting the associations between leptin, adiponectin, resistin, and ghrelin and the prevalence of general dementia, AD, and mild cognitive impairment (MCI). We also examined the relationship between the four gastrointestinal factors and neurocognitive outcomes and AD-related cerebrospinal fluid biomarkers. Patients with AD had lower blood leptin and higher resistin levels than cognitively normal participants. Lower leptin and higher resistin were associated with higher degree of cognitive impairment. Additionally, lower late-life leptin levels might be associated with higher prospective risk of dementia and AD, although more studies are needed to corroborate this. Results in ghrelin and adiponectin were not conclusive, with age, sex distribution, obesity, and severity of dementia seemingly acting as moderators across several analyses. Our work might contribute to the identification of new preclinical blood markers of MCI and AD.
Topics: Humans; Adipokines; Alzheimer Disease; Leptin; Resistin; Adiponectin; Ghrelin; Cross-Sectional Studies; Prospective Studies; Cognitive Dysfunction; Biomarkers; Obesity
PubMed: 37165483
DOI: 10.1111/obr.13573 -
BMC Immunology Oct 2023This systematic review aimed to map the evidence evaluated the relationship between vitamin D and redox and inflammatory status during gestation.
OBJECTIVE
This systematic review aimed to map the evidence evaluated the relationship between vitamin D and redox and inflammatory status during gestation.
METHODS
Three databases (PubMed/MEDLINE, Scopus, and Web of Science (WoS)) and reference list of included documents were searched for related observational studies published until 2nd October 2023. To determine the quality of the selected observational studies, the Newcastle-Ottawa Scale (NOS) was used.
RESULTS
After a primary search of three databases, 19492records were appeared. When duplicates and irrelevant documents were removed, 14 articles were found to have eligible criteria. The design of the identified studies was cross-sectional, case-control and cohort. Evidence showed an adverse association between 25(OH)D and the biomarkers of inflammation, such as high-sensitivity C-reactive protein (hs-CRP), Interleukin-1beta (IL-1β), Interleukin-6 (IL-6), and tumor necrosis factor- alfa (TNF-α) during pregnancy. On the contrary, some studies represented that 25(OH)D positively correlated with hs-CRP in the cord blood. One study suggested a direct association between serum concentrations of 25(OH)D and Interleukin-8 (IL-8), macrophage inflammatory protein (MIP), and TNF-α levels in mothers with gestational diabetes mellitus (GDM). A case-control study showed that lower serum concentration of 25(OH)D positively correlated with total antioxidant capacity (TAC) levels in participants.
CONCLUSIONS
Evidence confirmed the supposition of the direct relationship between vitamin D levels and biomarkers with anti-inflammatory and anti-oxidative properties. However, the Existence of inconsistent evidence confirms the need for further studies in mothers with GDM and hypertensive disorders.
PROSPERO REGISTRATION CODE
CRD42020202600.
Topics: Pregnancy; Female; Humans; Vitamin D; Pregnant Women; C-Reactive Protein; Tumor Necrosis Factor-alpha; Cross-Sectional Studies; Case-Control Studies; Vitamins; Biomarkers; Inflammation; Interleukin-6; Oxidative Stress
PubMed: 37891486
DOI: 10.1186/s12865-023-00577-w -
Inflammation Research : Official... May 2024γδ T cells are a distinct subset of unconventional T cells, which link innate and adaptive immunity by secreting cytokines and interacting with other immune cells,... (Review)
Review
OBJECTIVE
γδ T cells are a distinct subset of unconventional T cells, which link innate and adaptive immunity by secreting cytokines and interacting with other immune cells, thereby modulating immune responses. As the first line of host defense, γδ T cells are essential for mucosal homeostasis and immune surveillance. When abnormally activated or impaired, γδ T cells can contribute to pathogenic processes. Accumulating evidence has revealed substantial impacts of γδ T cells on the pathogenesis of cancers, infections, and immune-inflammatory diseases. γδ T cells exhibit dual roles in cancers, promoting or inhibiting tumor growth, depending on their phenotypes and the clinical stage of cancers. During infections, γδ T cells exert high cytotoxic activity in infectious diseases, which is essential for combating bacterial and viral infections by recognizing foreign antigens and activating other immune cells. γδ T cells are also implicated in the onset and progression of immune-inflammatory diseases. However, the specific involvement and underlying mechanisms of γδ T cells in oral diseases have not been systematically discussed.
METHODS
We conducted a systematic literature review using the PubMed/MEDLINE databases to identify and analyze relevant literature on the roles of γδ T cells in oral diseases.
RESULTS
The literature review revealed that γδ T cells play a pivotal role in maintaining oral mucosal homeostasis and are involved in the pathogenesis of oral cancers, periodontal diseases, graft-versus-host disease (GVHD), oral lichen planus (OLP), and oral candidiasis. γδ T cells mainly influence various pathophysiological processes, such as anti-tumor activity, eradication of infection, and immune response regulation.
CONCLUSION
This review focuses on the involvement of γδ T cells in oral diseases, with a particular emphasis on the main functions and underlying mechanisms by which γδ T cells influence the pathogenesis and progression of these conditions. This review underscores the potential of γδ T cells as therapeutic targets in managing oral health issues.
Topics: Humans; Mouth Diseases; Animals; Receptors, Antigen, T-Cell, gamma-delta; Intraepithelial Lymphocytes; Graft vs Host Disease; T-Lymphocytes
PubMed: 38563967
DOI: 10.1007/s00011-024-01870-z -
International Journal of Molecular... Oct 2023Bisphenols such as bisphenol A (BPA), S (BPS), C (BPC), F (BPF), AF (BPAF), tetrabromobisphenol, nonylphenol, and octylphenol are plasticizers used worldwide to... (Meta-Analysis)
Meta-Analysis Review
Bisphenols such as bisphenol A (BPA), S (BPS), C (BPC), F (BPF), AF (BPAF), tetrabromobisphenol, nonylphenol, and octylphenol are plasticizers used worldwide to manufacture daily-use articles. Exposure to these compounds is related to many pathologies of public health importance, such as infertility. Using a protector compound against the reproductive toxicological effects of bisphenols is of scientific interest. Melatonin and vitamins have been tested, but the results are not conclusive. To this end, this systematic review and meta-analysis compared the response of reproductive variables to melatonin and vitamin administration as protectors against damage caused by bisphenols. We search for controlled studies of male rats exposed to bisphenols to induce alterations in reproduction, with at least one intervention group receiving melatonin or vitamins (B, C, or E). Also, molecular docking simulations were performed between the androgen (AR) and estrogen receptors (ER), melatonin, and vitamins. About 1234 records were initially found; finally, 13 studies were qualified for review and meta-analysis. Melatonin plus bisphenol improves sperm concentration and viability of sperm and increases testosterone serum levels compared with control groups; however, groups receiving vitamins plus bisphenols had lower sperm concentration, total testis weight, and testosterone serum levels than the control. In the docking analysis, vitamin E had the highest negative MolDock score, representing the best binding affinity with AR and ER, compared with other vitamins and melatonin in the docking. Our findings suggest that vitamins could act as an endocrine disruptor, and melatonin is most effective in protecting against the toxic effects of bisphenols.
Topics: Male; Rats; Animals; Melatonin; Vitamins; Molecular Docking Simulation; Semen; Benzhydryl Compounds; Reproduction; Receptors, Estrogen; Vitamin A; Vitamin K; Testosterone; Endocrine Disruptors
PubMed: 37834378
DOI: 10.3390/ijms241914930 -
Infection Dec 2023Several studies suggested pancreatic stone protein (PSP) as a promising biomarker to predict mortality among patients with severe infection. The objective of the study... (Meta-Analysis)
Meta-Analysis
Discriminative performance of pancreatic stone protein in predicting ICU mortality and infection severity in adult patients with infection: a systematic review and individual patient level meta-analysis.
BACKGROUND
Several studies suggested pancreatic stone protein (PSP) as a promising biomarker to predict mortality among patients with severe infection. The objective of the study was to evaluate the performance of PSP in predicting intensive care unit (ICU) mortality and infection severity among critically ill adults admitted to the hospital for infection.
METHODS
A systematic search across Cochrane Central Register of Controlled Trials and MEDLINE databases (1966 to February 2022) for studies on PSP published in English using 'pancreatic stone protein', 'PSP', 'regenerative protein', 'lithostatin' combined with 'infection' and 'sepsis' found 46 records. The search was restricted to the five trials that measured PSP using the enzyme-linked immunosorbent assay technique (ELISA). We used Bayesian hierarchical regression models for pooled estimates and to predict mortality or disease severity using PSP, C-Reactive Protein (CRP) and procalcitonin (PCT) as main predictor. We used statistical discriminative measures, such as the area under the receiver operating characteristic curve (AUC) and classification plots.
RESULTS
Among the 678 patients included, the pooled ICU mortality was 17.8% (95% prediction interval 4.1% to 54.6%) with a between-study heterogeneity (I-squared 87%). PSP was strongly associated with ICU mortality (OR = 2.7, 95% credible interval (CrI) [1.3-6.0] per one standard deviation increase; age, gender and sepsis severity adjusted OR = 1.5, 95% CrI [0.98-2.8]). The AUC was 0.69 for PSP 95% confidence interval (CI) [0.64-0.74], 0.61 [0.56-0.66] for PCT and 0.52 [0.47-0.57] for CRP. The sensitivity was 0.96, 0.52, 0.30 for risk thresholds 0.1, 0.2 and 0.3; respective false positive rate values were 0.84, 0.25, 0.10.
CONCLUSIONS
We found that PSP showed a very good discriminative ability for both investigated study endpoints ICU mortality and infection severity; better in comparison to CRP, similar to PCT. Combinations of biomarkers did not improve their predictive ability.
Topics: Humans; Adult; Calcitonin; Lithostathine; Bayes Theorem; Prospective Studies; Biomarkers; C-Reactive Protein; Sepsis; Intensive Care Units; Procalcitonin; ROC Curve; Prognosis
PubMed: 37707744
DOI: 10.1007/s15010-023-02093-w -
Journal of Agricultural and Food... Nov 2023Alzheimer's disease (AD) is a neurodegenerative disease of the central nervous system that occurs in old age and pre-aging, characterized by progressive cognitive... (Meta-Analysis)
Meta-Analysis Review
Alzheimer's disease (AD) is a neurodegenerative disease of the central nervous system that occurs in old age and pre-aging, characterized by progressive cognitive dysfunction and behavioral impairment. Salidroside (Sal) is a phenylpropanoid mainly isolated from species with various pharmacological effects. However, the exact anti-AD mechanism of Sal has not been clearly elucidated. This meta-analysis aims to investigate the possible mechanisms by which Sal exerts its anti-AD effects by evaluating behavioral indicators and biochemical characteristics. A total of 20 studies were included, and the results showed that the Sal treatment significantly improved behavior abnormalities in AD animal models. With regard to neurobiochemical indicators, Sal treatment could effectively increase the antioxidant enzyme superoxide dismutase, decrease the oxidative stress indicator malondialdehyde, and decrease the inflammatory indicators interleukin 1β, interleukin 6, and tumor necrosis factor α. Sal treatment was effective in reducing neuropathological indicators, such as amyloid-β levels and the number of apoptotic cells. When the relevant literature on the treatment of rodent AD models is combined with Sal, the therapeutic potential of Sal through multiple mechanisms was confirmed. However, further confirmation by higher quality studies, larger sample sizes, and more comprehensive outcome evaluations in clinical trials is needed in the future.
Topics: Animals; Alzheimer Disease; Neurodegenerative Diseases; Oxidative Stress; Amyloid beta-Peptides; Neuroprotective Agents
PubMed: 37934032
DOI: 10.1021/acs.jafc.3c06672