Exercise-associated immune response plays a crucial role in the aging process. The aim of this study is to investigate the effect of sport intensity on cytokine levels, oxidative stress markers and telomere length in aging elite athletes. In this study, 80 blood samples from consenting elite athletes were collected for anti-doping analysis at an anti-doping laboratory in Italy (FMSI). Participants were divided into three groups according to their sport intensity: low-intensity skills and power sports (LI, n = 18); moderate-intensity mixed soccer players (MI, n = 31); and high-intensity endurance sports (HI, n = 31). Participants were also divided into two age groups: less than 25 (n = 45) and above 25 years old (n = 35). Serum levels of 10 pro and anti-inflammatory cytokines and two antioxidant enzymes were compared in age and sport intensity groups and telomere lengths were measured in their respective blood samples. Tumor necrosis factor-alpha (TNF-α) was the only cytokine showing significantly higher concentration in older athletes, regardless of sport intensity. Interleukin (IL)-10 increased significantly in HI regardless of age group, whereas IL-6 concentration was higher in the older HI athletes. IL-8 showed a significant interaction with sport intensity in different age groups. Overall, significant positive correlations among levels of IL-6, IL-10, IL-8 and TNF-α were identified. The antioxidant catalase activity was positively correlated with levels of TNF-α. Telomere length increased significantly with sport intensity, especially in the younger group. HI had longer telomeres and higher levels of pro- and anti-inflammatory cytokines, suggesting less aging in HI compared to low and moderate counterparts in association with heightened immune response. Investigation of the functional significance of these associations on the health and performance of elite athletes is warranted.

Impaired adipogenesis plays an important role in the development of obesity-associated insulin resistance and type 2 diabetes. Adipose tissue inflammation is a crucial mediator of this process. GATA-3 plays important roles in adipogenesis and inflammation. The aim of this study is to investigate the impact of GATA-3 suppression on improving adipogenesis, lowering inflammation and reversing insulin resistance. GATA-3 levels were measured in subcutaneous (SC) and omental (OM) adipose tissues obtained from insulin sensitive (IS) and insulin resistant (IR) obese individuals during weight reduction surgeries. The effect of GATA-3 suppression on adipogenesis, expression of inflammatory cytokines and insulin resistance biomarkers was performed in 3T3L-1 mouse preadipocytes via transfection with GATA-3-specific DNAzyme. GATA-3 expression was higher in OM compared to SC adipose tissues and in stromal vascular fraction-derived differentiating preadipocytes from IR obese individuals compared to their IS counterparts. Suppression of GATA-3 expression in 3T3L-1 mouse preadipocytes with GATA-3 specific inhibitor reversed 4-hydroxynonenal-induced impaired adipogenesis and triggered changes in the expression of insulin signaling-related genes. GATA-3 inhibition also modulated the expression of IL-6 and IL-10 and lowered the expression of insulin resistance biomarkers (PAI-1 and resistin) and insulin resistance phosphoproteins (p-BAD, p-PTEN and p-GSK3β). Inhibiting GATA-3 improves adipocytes differentiation, modulates the secretion of inflammatory cytokines and improves insulin sensitivity in insulin resistant cells. Suppression of GATA-3 could be a promising tool to improve adipogenesis, restore insulin sensitivity and lower obesity-associated inflammation in insulin resistant individuals.

Impaired adipogenesis is associated with the development of insulin resistance and an increased risk of type 2 diabetes (T2D). GATA Binding Protein 3 (GATA3) is implicated in impaired adipogenesis and the onset of insulin resistance. Therefore, we hypothesize that inhibition of GATA3 could promote adipogenesis, restore healthy fat distribution, and enhance insulin signaling. Primary human preadipocytes were treated with GATA3 inhibitor (DNAzyme hgd40). Cell proliferation, adipogenic capacity, gene expression, and insulin signaling were measured following well-established protocols. BALB/c mice were treated with DNAzyme hgd40 over a period of 2 weeks. Liposomes loaded with DNAzyme hgd40, pioglitazone (positive), or vehicle (negative) controls were administered subcutaneously every 2 days at the right thigh. At the end of the study, adipose tissues were collected and weighed from the site of injection, the opposite side, and the omental depot. Antioxidant enzyme (superoxide dismutase and catalase) activities were assessed in animals’ sera, and gene expression was measured using well-established protocols. In vitro GATA3 inhibition induced the adipogenesis of primary human preadipocytes and enhanced insulin signaling through the reduced expression of p70S6K. In vivo GATA3 inhibition promoted adipogenesis at the site of injection and reduced MCP-1 expression. GATA3 inhibition also reduced omental tissue size and PPARγ expression. These findings suggest that modulating GATA3 expression offers a potential therapeutic benefit by correcting impaired adipogenesis, promoting healthy fat distribution, improving insulin sensitivity, and potentially lowering the risk of T2D.

Obesity, characterized by excessive body fat, is closely linked to endoplasmic reticulum (ER) stress, leading to insulin resistance and type 2 diabetes. Inflammatory pathways like c-Jun N-terminal kinase (JNK) worsen insulin resistance, impacting insulin signaling. Moreover, ER stress plays a substantial role in cancer, influencing tumor cell survival and growth by releasing factors like vascular endothelial growth factor (VEGF). The unfolded protein response (UPR) is pivotal in this process, offering both pro-survival and apoptotic pathways. This review offers an extensive exploration of the sophisticated connection between ER stress provoked by obesity and its role in both the onset and advancement of cancer. It delves into the intricate interplay between oncogenic signaling and the pathways associated with ER stress in individuals who are obese. Furthermore, this review sheds light on potential therapeutic strategies aimed at managing ER stress induced by obesity, with a focus on addressing cancer initiation and progression. The potential to alleviate ER stress through therapeutic interventions, which may encompass the use of small molecules, FDA-approved medications, and gene therapy, holds great promise. A more in-depth examination of pathways such as UPR, ER-associated protein degradation (ERAD), autophagy, and epigenetic regulation has the potential to uncover innovative therapeutic approaches and the identification of predictive biomarkers.

Obesity plays a crucial role in the progression of insulin resistance and type 2 diabetes which are related to inflammation and liver disease. GATA-3 is a transcription factor that is involved in adipogenesis and inflammation. Therefore, it could be a potential therapeutic target for obesity-associated metabolic disorders. This study aimed to examine the effects of GATA-3 suppression on body weight, fat depot redistribution, liver histopathology, and inflammatory markers in transgenic db/db obese mice. Male db/db mice received subcutaneous injections of GATA-3-specific DNAzyme (hgd40; 10 or 100 µg/mL), pioglitazone (as a positive control), or vehicle only (as a negative control), twice weekly for two weeks. Body weight, organ weights, liver histopathology, mRNA expression of selected genes and serum cytokine levels were assessed. GATA-3 expression was not region specific, and its suppression did not significantly affect fat depot distribution or organ weights. However, the low dose of hgd40 accelerated body weight gain transiently. It also increased Il10 mRNA expression in the liver and significantly increased IL-10 protein concentration in the serum. In addition, a high dose of hgd40 resulted in a marked decrease in hepatocyte ballooning degeneration. These findings suggest that GATA-3 suppression may modulate inflammation and liver injury in obesity, warranting further investigation into its therapeutic potential for obesity-related metabolic disorders.

Breast cancer is a global health concern, including in Qatar, where it impacts women significantly. The complexity of breast cancer requires diverse treatment approaches influenced by tumor characteristics and biology. Despite advancements, current treatments still fall short of providing definitive solutions, particularly for triple-negative breast cancer. Complementary and Alternative Medicine (CAM), including herbal remedies, is increasingly popular among cancer patients, including those in Qatar. In Qatar, herbal medicine is widely used by the population, including breast cancer patients, yet preserving this knowledge faces significant challenges. This study aimed to document herbalists' ethnobotanical practices concerning breast cancer treatment in Qatar and corroborate any identified plant remedies' anticancer use with the literature. Thirteen herbalists were identified in Doha, Qatar, and surveyed using an ethnobotanical questionnaire between October and November 2022. Herbalists’ demographic data and their herbal recommendations for breast cancer treatment were collected through structured interviews. Descriptive statistics and the Relative Frequency Citation (RFC) were employed for data analysis. The current study aimed to document herbalists' practices for breast cancer management in Qatar and validate the anticancer potential of the identified plants through existing literature. The present study documented the ethnobotanical knowledge of 13 herbalists in Qatar regarding breast cancer treatment, revealing the use of various plant species from ten different families. Saussurea costus (Falc.) Lipsch. (Al Qist Al Hindi), Zingiber officinale Roscoe (Ginger) (zanjabel) and Nigella sativa L. (Black seeds) (habit elbaraka) were the most recommended plants.