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Phytomedicine : International Journal... May 2024Extensive research on Lupeol's potential in cancer prevention highlights its ability to target various cancer-related factors. It regulates proliferative markers,... (Review)
Review
BACKGROUND
Extensive research on Lupeol's potential in cancer prevention highlights its ability to target various cancer-related factors. It regulates proliferative markers, modulates signaling pathways, including PI3K/AKT/mTOR, and influences inflammatory and apoptotic mechanisms. Additionally, Lupeol demonstrates selectivity in killing cancer cells while sparing normal cells, thus minimizing the risk of toxic effects on healthy tissues.
HYPOTHESIS
Therefore, we aimed to explore Lupeol's potential roles as a chemotherapeutic agent and as a sensitizer to chemotherapy by reviewing various animal-based studies published on its effects.
STUDY DESIGN
We conducted a comprehensive search across databases, including PubMed, PMC, Cochrane, EuroPMC, and ctri.gov.in to identify pertinent articles. Our focus was solely on published animal studies examining Lupeol's anti-cancer effects, with reviewers independently assessing bias risk and resolving discrepancies through consensus.
RESULT
20 studies were shortlisted. The results demonstrated that Lupeol brings changes in the tumor volume by [Hedges's g: -6.62; 95 % CI: -8.68, -4.56; τ: 24.36, I: 96.50 %; p < 0.05] and tumor weight by [Hedges's g: -3.97; 95 % CI: -5.20, -2.49; τ: 2.70, I: 79.27 %; p <0.05]. The high I, negative Egger's value, and asymmetrical funnel plot show the publication bias among the studies. Further, Lupeol in combination with other chemotherapeutic agents showed better outcomes as compared to them alone [Hedges's g: -6.38; 95 % CI: -11.82, -0.94; τ: 46.91; I: 98.68 %; p <0.05]. Lupeol also targets various signaling molecules and pathways to exert an anti-cancer effect.
CONCLUSION
In conclusion, Lupeol significantly reduces tumor volume and weight. Combining Lupeol with other chemotherapy agents shows promise for enhancing anti-cancer effects. However, high variability among studies and evidence of publication bias suggest caution in interpreting results.
PubMed: 38943695
DOI: 10.1016/j.phymed.2024.155777 -
JACC. Advances Feb 2024Cystatin C, neutrophil gelatinase-associated lipocalin (NGAL), and kidney injury molecule (KIM)-1 are renal biomarkers increasingly appreciated for their role in the...
BACKGROUND
Cystatin C, neutrophil gelatinase-associated lipocalin (NGAL), and kidney injury molecule (KIM)-1 are renal biomarkers increasingly appreciated for their role in the risk stratification and prognostication of heart failure (HF) patients. However, very few have been adopted clinically, owing to the lack of consistency.
OBJECTIVES
The authors aimed to study the association between cystatin C, NGAL, and KIM-1 and outcomes, mortality, hospitalizations, and worsening renal function (WRF) in patients with acute and chronic HF.
METHODS
We included peer-reviewed English-language articles from PubMed and EMBASE published up to December 2021. We analyzed the above associations using random-effects meta-analysis. Publication bias was assessed using funnel plots.
RESULTS
Among 2,631 articles, 100 articles, including 45,428 patients, met the inclusion criteria. Top-tertile of serum cystatin C, when compared to the bottom-tertile, carried a higher pooled hazard ratio (pHR) for mortality (pHR: 1.59, 95% CI: 1.42-1.77) and for the composite outcome of mortality and HF hospitalizations (pHR: 1.49, 95% CI: 1.23-1.75). Top-tertile of serum NGAL had a higher hazard for mortality (pHR: 2.91, 95% CI: 1.49-5.67) and composite outcome (HR: 4.11, 95% CI: 2.69-6.30). Serum and urine NGAL were significantly associated with WRF, with pHRs of 2.40 (95% CI: 1.48-3.90) and 2.01 (95% CI: 1.21-3.35). Urine KIM-1 was significantly associated with WRF (pHR: 1.60, 95% CI: 1.24-2.07) but not with other outcomes. High heterogeneity was noted between studies without an obvious explanation based on meta-regression.
CONCLUSIONS
Serum cystatin C and serum NGAL are independent predictors of adverse outcomes in HF. Serum and urine NGAL are important predictors of WRF in HF.
PubMed: 38939376
DOI: 10.1016/j.jacadv.2023.100765 -
Journal of Diabetes and Metabolic... Jun 2024Metabolic syndrome (MetS) is a cluster of physiological, biochemical, clinical, and metabolic conditions that aggravate the risk of severe diseases such as...
BACKGROUND
Metabolic syndrome (MetS) is a cluster of physiological, biochemical, clinical, and metabolic conditions that aggravate the risk of severe diseases such as cardiovascular disease, type 2 diabetes mellitus, and fatty liver. Several dietary molecules have been considered preventive compounds for MetS. Anethole, a natural phenylpropanoid, has been found to protect against MetS and its associated components.
AIM
This systematic review aims to provide an overview of the preclinical evidence supporting the protective effects of dietary anethole against MetS and the associated diseases.
METHODS
A literature search was performed using Web of Sciences, PubMed, Scopus, and Google Scholar to identify studies reporting the protective effects of dietary anethole against MetS, without any time restrictions. Review articles, letters to editors, editorials, unpublished results, and non-English papers were excluded from the study.
RESULTS
The results showed that anethole has the potential to effectively protect against the key features of MetS via various mechanisms, including antioxidant and anti-inflammatory effects, stimulating insulin secretion from β-cells, mediating oxidative stress, modulation of the mTOR/PPARγ axis, arterial remodeling, and improvement of vascular relaxation.
CONCLUSION
Anethole modulates several molecular pathways that are implicated in the pathogenesis of MetS. Future in vitro and animal investigations should be conducted to explore other anti-MetS signaling pathways of anethole. Additionally, well-designed clinical studies are warranted to determine the optimal human dose, bioavailability, and pharmacokinetic characteristics of this dietary compound.
PubMed: 38932801
DOI: 10.1007/s40200-023-01322-1 -
Molecules (Basel, Switzerland) Jun 2024Our hypothesis that controlled ozone applications interfere with the redox balance of a biological organism (first published in 1998 with a preclinical trial on... (Review)
Review
Our hypothesis that controlled ozone applications interfere with the redox balance of a biological organism (first published in 1998 with a preclinical trial on protecting the liver from CCl intoxication) has been verified over the past two decades in reactive oxygen species (ROS)-induced mitochondrial pathologies, such as rheumatoid arthritis, osteoarthritis, aging processes and type 2 diabetes, and in the prevention of intoxications. Low-dose ozone acts as a redox bioregulator: the restoration of the disturbed redox balance is comprehensible in a number of preclinical and clinical studies by a remarkable increase in the antioxidant repair markers, here mainly shown as a glutathione increase and a reduction in oxidative stress markers, mainly malondialdehyde. The mechanism of action is shown, and relevant data are displayed, evaluated and comprehensively discussed: the repair side of the equilibrium increases by 21% up to 140% compared to the non-ozone-treated groups and depending on the indication, the stress markers are simultaneously reduced, and the redox system regains its balance.
Topics: Oxidative Stress; Ozone; Oxidation-Reduction; Humans; Mitochondria; Reactive Oxygen Species; Animals; Antioxidants; Biomarkers
PubMed: 38930804
DOI: 10.3390/molecules29122738 -
Cureus May 2024(NS), commonly known as black cumin or black seed, is a medicinal plant with a rich history of traditional use in various cultures. Recent research has shed light on... (Review)
Review
(NS), commonly known as black cumin or black seed, is a medicinal plant with a rich history of traditional use in various cultures. Recent research has shed light on its potential therapeutic properties, particularly its effects on endothelial markers involved in inflammatory processes. This systematic review and meta-analysis evaluated the endothelial function responses, including intercellular adhesion molecule (ICAM) and vascular cell adhesion molecule (VCAM), to NS supplementation. We systematically searched Medline via PubMed, Scopus, Web of Science, and Embase databases from inception until August 5, 2023. Comparative randomized controlled trials (RCTs) were included. Pairwise meta-analysis was conducted using RevMan version 5.4 for Windows. Pooled data were reported as mean difference (MD), with their 95% confidence interval (CI). The present meta-analysis included three RCTs, which included 146 patients. The pooled random-effect size showed no difference between the NS group and the control group in terms of ICAM (MD = -59.32, 95% CI: -137.18 to 18.54; p = 0.14) and VCAM (MD = -200.1, 95% CI: -429.9 to 29.69; p = 0.09). The pooled data were severely heterogeneous. In conclusion, NS supplementation does not have a significant impact on the endothelial function of patients with CVD or the risks of CVD. Further comparative RCTs with larger sample sizes and more diverse populations are needed to establish the efficacy and safety of NS in different clinical settings.
PubMed: 38915995
DOI: 10.7759/cureus.61047 -
Journal of Experimental Orthopaedics Jul 2024The purpose of this study was to quantify and compare the clinical relevance of the different intra-articular corticosteroids (CS) effects in vivo for osteoarthritis... (Review)
Review
PURPOSE
The purpose of this study was to quantify and compare the clinical relevance of the different intra-articular corticosteroids (CS) effects in vivo for osteoarthritis (OA) treatment.
METHODS
The search was conducted on PubMed, Cochrane, and Web of Science in October 2023. The PRISMA guidelines were used. Inclusion criteria: animal or human randomized controlled trials (RCTs), English language and no time limitation, on the comparison of different intra-articular CS for OA treatment. The articles' quality was assessed using the Cochrane RoB2 and GRADE guidelines for human RCTs, and SYRCLE's tool for animal RCTs.
RESULTS
Eighteen RCTs were selected (16 human and 2 animal studies), including 1577 patients (1837 joints) and 31 animals (51 joints). The CS used were triamcinolone (14 human and 2 animal studies), methylprednisolone (7 human and 1 animal study), betamethasone (3 human studies) and dexamethasone (1 human study). All studies addressed knee OA except for three human and one animal study. A meta-analysis was performed on the comparison of methylprednisolone and triamcinolone in humans with knee OA analysing VAS pain at very short- (≤2 weeks), short- (>2 and ≤4 weeks), mid- (>4 and ≤8 weeks), long- (>8 and ≤ 12 weeks), and very long-term (>12 and ≤24 weeks). Triamcinolone showed better post-injection values compared to methylprednisolone at very short-term ( = 0.028). No difference in terms of VAS improvement was observed at any follow-up.
CONCLUSIONS
The available preclinical and clinical literature provides limited evidence on the comparison of different CS, hindering the possibility of determining the best CS approach in terms of molecule and dose for the intra-articular injection of OA joints.
LEVEL OF EVIDENCE
Level I.
PubMed: 38911187
DOI: 10.1002/jeo2.12060 -
Proceedings (Baylor University. Medical... 2024Colorectal cancer (CRC) presents significant mortality risks, underscoring the urgency of timely diagnosis and intervention. Advanced stages of CRC are managed through...
Colorectal cancer (CRC) presents significant mortality risks, underscoring the urgency of timely diagnosis and intervention. Advanced stages of CRC are managed through chemotherapy, targeted therapy, immunotherapy, radiotherapy, and surgery. Immunotherapy, while effective in bolstering the immune system against cancer cells, often carries toxic side effects, including colitis. This study aimed to evaluate the incidence of colitis in patients with metastatic CRC (mCRC) undergoing various immunotherapy treatments. Through a systematic search of Google Scholar and PubMed databases from inception until November 2023, nine relevant studies were identified. Subgroup analyses revealed a higher incidence of colitis, particularly in patients treated with anti-cytotoxic T-lymphocyte-associated molecule-4 (anti-CTLA-4) and combination therapies compared to monotherapy with programmed cell death receptor-1 (PD-1) or programmed cell death ligand receptor-1 (PDL-1) inhibitors. Notably, naive-treated metastatic CRC patients exhibited elevated colitis incidences compared to those previously treated. In conclusion, anti-CTLA-4 and combination therapies, such as nivolumab plus ipilimumab, were associated with increased colitis occurrences in metastatic CRC patients, highlighting the need for vigilant monitoring and management strategies, especially in immunotherapy-naive individuals.
PubMed: 38910824
DOI: 10.1080/08998280.2024.2342723 -
Dermatology and Therapy Jun 2024New advancements in medicine have paved the way for targeted therapies and immune checkpoint inhibitors (ICIs), which have become mainstays of cancer therapy. Targeted... (Review)
Review
Psoriasis in the Era of Targeted Cancer Therapeutics: A Systematic Review on De Novo and Pre-existing Psoriasis in Oncologic Patients Treated with Emerging Anti-neoplastic Agents.
New advancements in medicine have paved the way for targeted therapies and immune checkpoint inhibitors (ICIs), which have become mainstays of cancer therapy. Targeted therapies work by pinpointing specific molecules in cancer pathways and inhibiting their function, while ICIs target irregularities in the immune system and DNA repair, participating in the induction of cell death. Although these agents have demonstrated great efficacy in treating a diverse set of cancers, they can frequently provoke serious dermatologic adverse effects. The side effects caused by an ICI are classified as immune-related adverse events since ICIs are immunomodulating, while the cutaneous side effects of targeted therapies are known as dermatologic adverse effects. Multiple studies have reported psoriasis and psoriasiform eruptions among the side effects observed in neoplastic patients receiving targeted therapies or ICIs. Psoriasis is an immune-mediated disease characterized by overactive T-cells and keratinocytes. To conduct this review, we retrieved 1363 studies from the PubMed database published between 2008 and 2023 using the terms "psoriasis" AND "cancer treatment." Many of these studies aimed to understand how patients with cancer receiving treatment may develop or even achieve psoriasis remission. Given that cancer and psoriasis involve a delicate balance between immune activation and suppression, ICIs and targeted therapies might produce varying effects. The aim of this review was to explore the relationship between psoriasis and cancer therapeutics while also highlighting the need to prioritize proper management of cutaneous side effects in neoplastic patients.
PubMed: 38907875
DOI: 10.1007/s13555-024-01198-w -
Kidney International Reports Jun 2024Chronic kidney disease of uncertain etiology (CKDu) is an incompletely defined phenotype of chronic kidney disease (CKD) affecting young individuals mostly in...
INTRODUCTION
Chronic kidney disease of uncertain etiology (CKDu) is an incompletely defined phenotype of chronic kidney disease (CKD) affecting young individuals mostly in agricultural communities in Central America and South Asia. CKDu is a diagnosis of exclusion made in individuals from endemic regions.
METHODS
We conducted a systematic review of the primary literature on urinary and plasma kidney injury biomarkers measured in the setting of CKDu (through February 2023). The literature was identified via a Web of Science search and hand search of the references of previously identified literature. Search terms included "CKDu," "Mesoamerican Nephropathy," "CKD of unknown etiology," "Chronic Interstitial Nephritis in Agricultural Communities," "biomarker," "urin∗," and/or "plasma."
RESULTS
A total of 25 papers were included. The 2 most frequently measured biomarkers were urinary kidney injury molecule-1 (KIM-1) and urinary neutrophil gelatinase-associated lipocalin (NGAL). There was substantial variability in study design, laboratory assay methods, and statistical methodology, which prohibited meta-analysis.
CONCLUSION
Biomarkers that identify tubulointerstitial disease early and accurately may substantially accelerate progress in the study of CKDu and facilitate public health approaches that eventually lead to its prevention and elimination. To date, the literature is limited by relatively small sample sizes and methodological limitations which should be addressed in future studies.
PubMed: 38899184
DOI: 10.1016/j.ekir.2024.03.013 -
Journal of Affective Disorders Jun 2024Bipolar disorders (BD) are chronic, debilitating disorders. The blood-brain barrier (BBB) has been increasingly investigated in BD. This systematic review aimed to... (Review)
Review
BACKGROUND
Bipolar disorders (BD) are chronic, debilitating disorders. The blood-brain barrier (BBB) has been increasingly investigated in BD. This systematic review aimed to assess the available evidence on the relationship between BD and markers of BBB dysfunction.
METHODS
A systematic search in PubMed, Embase, PsycINFO, CINAHL and Web of Science was run where the primary outcomes were BBB markers such as S100B, albumin ratio, matrix metalloproteinase (MMP), cell adhesion molecule (CAM), and tight junction proteins. Techniques included blood, cerebrospinal fluid (CSF), post-mortem, genetic and imaging methods in BD compared to healthy controls.
RESULTS
55 studies were identified, 38 of which found an association between BD and markers of BBB dysfunction. 16/29 studies found increased blood/CSF albumin ratio, S100B, CAMs or MMP levels in BD participants compared to controls. 5/19 post-mortem studies found increased levels of chondroitin sulphate proteoglycans, intercellular CAM, neurexin or claudin-5 mRNA in distinct locations throughout the brain in BD compared to controls. One imaging study identified extensive BBB leakage in 30 % of BD participants, compared to 0 % in controls.
LIMITATIONS
The diversity in methodologies used in the included studies makes direct comparison of results challenging. Furthermore, imaging methods are the gold standard, but only one study used them. Other markers are only indicative of BBB permeability.
CONCLUSIONS
This review suggests an association between BD and BBB dysfunction. Further research is needed to provide definite answers considering the existing literature's limitations, and to clarify whether this association provides a pathogenic mechanism, or is an epiphenomenon of BD.
PubMed: 38897301
DOI: 10.1016/j.jad.2024.06.032