Dietary Interventions with Polyphenols in Osteoarthritis: A Systematic Review Directed from the Preclinical Data to Randomized Clinical Studies

Osteoarthritis (OA) is the most common form of arthritis and a major cause of limited functionality and thus a decrease in the quality of life of the inflicted. Given the fact that the existing pharmacological treatments lack disease-modifying properties and their use entails significant side effects, nutraceuticals with bioactive compounds constitute an interesting field of research. Polyphenols are plant-derived molecules with established anti-inflammatory and antioxidant properties that have been extensively evaluated in clinical settings and preclinical models in OA. As more knowledge is gained in the research field, an interesting approach in the management of OA is the additive and/or synergistic effects that polyphenols may have in an optimized supplement. Therefore, the aim of this review was to summarize the recent literature regarding the use of combined polyphenols in the management of OA. For that purpose, a PubMed literature survey was conducted with a focus on some preclinical osteoarthritis models and randomized clinical trials on patients with osteoarthritis from 2018 to 2021 which have evaluated the effect of combinations of polyphenol-rich extracts and purified polyphenol constituents. Data indicate that combined polyphenols may be promising for the treatment of osteoarthritis in the future, but more clinical trials with novel approaches in the identification of the in-between relationship of such constituents are needed.     

Switching between biologics in severe asthma patients. When the first choice is not proven to be the best

During the last decades, new treatments targeting disease mechanisms referred as biologics have been introduced in the therapy of asthma and currently, five monoclonal antibodies have been approved. Although these therapeutic agents have been formulated to target specific asthma endotypes, it is often difficult for the treating physician to identify which patient is the best candidate for each one of these specific treatments especially in the clinical scenario of a patient in whom clinical characteristics overlap between different endotypes, allowing the selection of more than one biologic agent. As no head-to-head comparisons between these biologics have been attempted, there is no evidence on the superiority of one biologic agent over the other. Furthermore, a physician's first therapeutic decision, no matter how carefully has been made, may often result in suboptimal clinical response and drug discontinuation, indicating the need for switching to a different biologic. In this short review, we discuss the available evidence regarding the switching between biologics in patients with severe asthma and we propose a simple algorithm on switching possibilities in case that the physicians’ initial choice is proven not to be the best.     

Effect of Greek Raisins (Vitis Vinifera L.) From Different Origins on Gastric Cancer Cell Growth

Currants and Sultanas (Vitis vinifera L.) are dried vine products produced in Greece and used broadly in the Mediterranean diet. We aimed to investigate the gastric cancer preventive activity of methanol extracts obtained from currants from three different origins in Greece (Vostizza, Nemea, and Messinia) as well as methanol extracts obtained from Sultanas cultivated in the island of Crete as to inhibition of cell proliferation, induction of apoptosis, and inhibition of inflammation. All extracts from 500 μg dried raisins studied suppressed cell proliferation, significantly those obtained from Sultanas from Crete and currants from Nemea. Flow cytometric analysis of Annexin-V labeled cells indicated that Cretan Sultana, Nemea, and Messinia currants at 500 μg dried product/ml medium significantly induced cell death. All extracts from 500 μg dried raisins statistically decreased protein and mRNA levels of ICAM-1 in TNF-alpha stimulated cells. Measurement of IL-8 protein levels and quantification for IL-8 mRNA showed no significant decrease. These results indicate that the methanol extracts from currants, rich in phenolic compounds, exhibit cancer preventive efficacy by limiting cell proliferation, inducing cell death, and suppressing ICAM-1 levels in AGS cells.     

High‐frequency p16INK4A promoter methylation is associated with histone methyltransferase SETDB1 expression in sporadic cutaneous melanoma

Epigenetic mechanisms participate in melanoma development and progression. The effect of histone modifications and their catalysing enzymes over euchromatic promoter DNA methylation in melanoma remains unclear. This study investigated the potential association of p16^INK4A promoter methylation with histone methyltransferase SETDB1 expression in Greek patients with sporadic melanoma and their correlation with clinicopathological characteristics. Promoter methylation was detected by methylation‐specific PCR in 100 peripheral blood samples and 58 melanoma tissues from the same patients. Cell proliferation (Ki‐67 index), p16^INK4A and SETDB1 expression were evaluated by immunohistochemistry. High‐frequency promoter methylation (25.86%) was observed in tissue samples and correlated with increased cell proliferation (P = 0.0514). p16^INK4A promoter methylation was higher in vertical growth‐phase (60%) melanomas than in radial (40%, P = 0.063) and those displaying epidermal involvement (P = 0.046). Importantly, p16^INK4A methylation correlated with increased melanoma thickness according to Breslow index (P = 0.0495) and marginally with increased Clark level (I/II vs III/IV/V, P = 0.070). Low (1–30%) p16^INK4A expression was detected at the majority (19 of 54) of melanoma cases (35.19%), being marginally correlated with tumor lymphocytic infiltration (P = 0.078). SETDB1 nuclear immunoreactivity was observed in 47 of 57 (82.46%) cases, whereas 27 of 57 (47.37%) showed cytoplasmic immunoexpression. Cytoplasmic SETDB1 expression correlated with higher frequency of p16^INK4A methylation and p16^INK4A expression (P = 0.033, P = 0.011, respectively). Increased nuclear SETDB1 levels were associated with higher mitotic count (0–5/mm² vs >5/mm², P = 0.0869), advanced Clark level (III‐V, P = 0.0380), epidermal involvement (P = 0.0331) and the non‐chronic sun exposure‐associated melanoma type (P = 0.0664). Our data demonstrate for the first time the association of histone methyltransferase SETDB1 with frequent methylation of the euchromatic p16^INK4A promoter and several prognostic parameters in melanomas.     

The use of rheumatoid arthritis health‐related quality of life patient questionnaires in clinical practice: Lessons learned

Objective

The utilization of health‐related quality of life (HRQOL) patient questionnaires by clinical rheumatologists is limited. Yet, considerable literature exists defining the value of such data. In an effort to understand this apparent paradox, we performed a literature review and conducted a survey to describe what has been learned over the past 2 decades concerning the use of these measures in clinical care and explore the reasons for their underutilization.

Methods

A panel of rheumatologists with extensive clinical experience was convened to review the relevant literature pertaining to the use of HRQOL patient instruments in clinical practice. Additionally, a survey of all American College of Rheumatology practicing clinicians was conducted to assess the use of and beliefs about these measures.

Results

The literature provided evidence to support the use of HRQOL patient measures in clinical practice. Forty‐seven percent of the responding rheumatologists stated that none of their patients complete HRQOL patient questionnaires. The majority of respondents (63%) reported that such information is “somewhat valuable.” The most frequently reported reason for the underutilization was that such instruments “require too much staff time.”

Conclusions

The literature supports the potential value of HRQOL patient questionnaires in clinical practice. Few rheumatologists routinely gather such information as part of patient care. Reasons for this discrepancy between utility and use are given along with recommendations intended to help increase their utilization in clinical care.

     

Antiatherogenic effect of Pistacia lentiscus via GSH restoration and downregulation of CD36 mRNA expression

Pistacia lentiscus var. Chia (Anacardiaceae) grows almost exclusively on Chios Island, Greece, and gives a resinous exudate resin used for culinary purposes by Mediterranean people. We investigated the molecular mechanisms through which total polar extract of the resin inhibits oxidized low-density lipoprotein (oxLDL) cytotoxic effect on peripheral blood mononuclear cell (PBMC). Cells exposed to oxLDL underwent apoptosis and necrosis, dependent on the duration of exposure. When culturing cells with oxLDL and the polar extract concurrently, we observed inhibition of both the phenomena. Because under oxidative stress the pro-oxidant systems outbalance the antioxidant, potentially producing oxidative damage and ultimately leading to cell death, we measured the levels of intracellular antioxidant glutathione (GSH). Additionally, we measured CD36 expression, a class B scavenger receptor, on CD14-positive cells, as CD36 has been identified as the oxLDL receptor in macrophages and may play a pivotal role in atherosclerotic foam cell formation. oxLDL decreased GSH levels and upregulated CD36 expression. P. lentiscus extract restored GSH levels and downregulated CD36 expression, even at the mRNA level. In order to find out the biologically drastic constituents of the resin's polar extract, fractions derived from RP-HPLC analysis were examined for their antioxidant effect on oxidatively stressed PBMC. The triterpenoid fraction revealed remarkable increase in intracellular GSH. We suggest GSH restoration and downregulation of CD36 mRNA expression as the pathways via which P. lentiscus triterpenes exert antioxidant/antiatherogenic effect. Additionally, our results provide strong evidence of the resin's antiatherogenic effect; therefore it is credited with beneficial health aspects.     

Effects of mono(2-ethylhexyl) phthalate (MEHP) on testes in rats in vitro

The phthalate esters have been used as plasticizers for various plastic products, and their testicular toxicity has been reported. In this study, the effects of mono(2-ethylhexyl) phthalate (MEHP), one of the phthalate esters, on prepubertal rat testes in vitro were examined. The testes of 20-day-old Sprague Dawley (SD) rats were cut into smaller pieces and seeded in medium, and then the specimens were obtained for light and transmission electron microscopic observations. As a result, at 1 hr after exposure to MEHP, TUNEL-positive spermatogenic cells were identified, and they gradually increased in number in time- and dose-dependent manners. Ultrastructurally, apoptotic spermatogenic cells (characterized with chromatin condensation, cytoplasm shrinkage without membrane rupture, still-functioning cell organelles, and packed cell contents in membrane-bounded bodies), necrotic spermatogenic cells (characterized with swollen and ruptured mitochondria, plasma membrane lysis, spilt cell contents, and chromatin clumps), apoptotic Sertoli cells (highly condensed nuclei and nuclear membrane lysis) and necrotic Sertoli cells (marginated chromatins along the nuclear membrane, some swollen and ruptured cell organelles, e.g. mitochondria) could be identified. Conclusively, based on transmission electron microscopic observations, MEHP treatment may affect spermatogenic cells, and lead them to necrosis. Thus, testicular tissue cultures and cell cultures are of advantageous for screening testicular toxicity of chemicals.     

Effects of long-term consumption and single meals of chickpeas on plasma glucose, insulin, and triacylglycerol concentrations

BACKGROUND: Legumes are recommended for better glucose control in persons with diabetes. Whether subjects with normal insulin sensitivity would also benefit from legume consumption is not clear. OBJECTIVE: Our goal was to compare the effects on insulin sensitivity of chickpea-based and wheat-based foods when eaten as single meals or over 6 wk. DESIGN: Acute and long-term studies were conducted in healthy middle-aged men and women. In the acute study (n = 19), plasma glucose, insulin, and calculated homeostasis model assessment (HOMA; an index of insulin sensitivity) were measured on 3 separated days over 3 h after the subjects consumed 50-g available carbohydrate loads from either chickpeas, wheat-based foods, or white bread. The long-term comparison (n = 20) was a randomized, crossover study in which chickpea-based and wheat-based foods were eaten for 6 wk each. Plasma glucose, insulin, and HOMA were measured in the fasting state and 2 h after a 75-g glucose load. RESULTS: After single meals, plasma glucose was substantially lower 30 and 60 min after the chickpea meal than after the other 2 meals (P < 0.05), and plasma insulin and HOMA were lower at 120 min (P < 0.05 for both). Despite this, the long-term study failed to show significant differences in plasma glucose, insulin, or HOMA either in the fasting state or after a glucose load. CONCLUSION: Compared with a wheat-based meal, a single chickpea-based meal led to a lesser response in plasma glucose and insulin concentrations, but this was not translated into long-term improvement in insulin sensitivity over 6 wk, at least in healthy subjects.