Apigenin's Modulation of Doxorubicin Efficacy in Breast Cancer.

Apigenin, a naturally derived flavonoid, is increasingly being acknowledged for its potential therapeutic applications, especially in oncology. This research explores apigenin's capacity to modulate cancer cell viability, emphasizing its roles beyond its minimal antioxidant activity attributed to its basic molecular structure devoid of hydroxyl groups. We investigated apigenin's effects on two breast cancer cell lines, estrogen-dependent MCF-7 and non-estrogen-dependent MDA-MB-231 cells. Our findings reveal that apigenin exerts a dose-dependent cytotoxic and anti-migratory impact on these cells. Interestingly, both apigenin and doxorubicin-a standard chemotherapeutic agent-induced lipid droplet accumulation in a dose-dependent manner in MDA-MB-231 cells. This phenomenon was absent in MCF-7 cells and not evident when doxorubicin and apigenin were used concurrently, suggesting distinct cellular responses to these treatments that imply that their synergistic effects might be mediated through mechanisms unrelated to lipid metabolism. A further chemoinformatics analysis indicated that apigenin and doxorubicin might interact primarily at the level of ATP-binding cassette (ABC) transporter proteins, with potential indirect influences from the AKT and MYC signaling pathways. These results highlight the importance of understanding the nuanced interactions between apigenin and conventional chemotherapeutic drugs, as they could lead to more effective strategies for cancer treatment. This study underscores apigenin's potential as a modulator of cancer cell dynamics through mechanisms independent of its direct antioxidant effects, thereby contributing to the development of flavonoid-based adjunct therapies in cancer management.

Dietary factors and their influence on immunotherapy strategies in oncology: a comprehensive review.

Immunotherapy is emerging as a promising avenue in oncology, gaining increasing importance and offering substantial advantages when compared to chemotherapy or radiotherapy. However, in the context of immunotherapy, there is the potential for the immune system to either support or hinder the administered treatment. This review encompasses recent and pivotal studies that assess the influence of dietary elements, including vitamins, fatty acids, nutrients, small dietary molecules, dietary patterns, and caloric restriction, on the ability to modulate immune responses. Furthermore, the article underscores how these dietary factors have the potential to modify and enhance the effectiveness of anticancer immunotherapy. It emphasizes the necessity for additional research to comprehend the underlying mechanisms for optimizing the efficacy of anticancer therapy and defining dietary strategies that may reduce cancer-related morbidity and mortality. Persistent investigation in this field holds significant promise for improving cancer treatment outcomes and maximizing the benefits of immunotherapy.

Biomaterials in Cancer Therapy: Investigating the Interaction between Kaempferol and Zinc Ions through Computational, Spectroscopic and Biological Analyses.

A complex of the natural flavonoid kaempferol with zinc (Kam-Zn) was synthesized, and its physicochemical properties were investigated using spectroscopic methods such as Fourier transform infrared spectroscopy (FT-IR), ultraviolet-visible (UV-Vis) spectroscopy and theoretical chemistry. Biological studies were conducted to evaluate the cytotoxic and antiproliferative effects of these complexes on MCF-7 breast cancer cells. Treatment with Kam 100 µM (84.86 ± 7.79%; 64.37 ± 8.24%) and Kam-Zn 100 µM (91.87 ± 3.80%; 87.04 ± 13.0%) showed no significant difference in proliferation between 16 h and 32 h, with the gap width remaining stable. Both Kam-Zn 100 µM and 200 µM demonstrated effective antiproliferative and cytotoxic activity, significantly decreasing cell viability and causing cell death and morphology changes. Antioxidant assays revealed that Kam (IC50 = 5.63 ± 0.06) exhibited higher antioxidant potential compared to Kam-Zn (IC50 = 6.80 ± 0.075), suggesting that zinc coordination impacts the flavonoid's radical scavenging activity by the coordination of metal ion to hydroxyl groups. Computational studies revealed significant modifications in the electronic structure and properties of Kam upon forming 1:1 complexes with Zn2+ ions. Spectroscopy analyses confirmed structural changes, highlighting shifts in absorption peaks and alterations in functional group vibrations indicative of metal-ligand interactions. FT-IR and UV-Vis spectra analysis suggested that Zn coordinates with the 3-OH and 4C=O groups of ligand. These findings suggest that the Kam-Zn complex exhibits interesting antiproliferative, cytotoxic and modified antioxidant effects on MCF-7 cells, providing valuable insights into their structural and anticancer properties.

The Influence of Lifestyle on Male Fertility in the Context of Insulin Resistance-Identification of Factors That Influence Semen Quality.

Background: Male fertility is known to have been negatively influenced by the progress of civilization. Another condition whose incidence has been on the increase for the same reason is insulin resistance (IR). In addition, men increasingly often resign from the pursuit of active forms of leisure, preferring more sedentary ones. Considering these trends, this aim of this study was to investigate the relationships between lifestyle factors, insulin resistance, and male fertility in men with and without the condition. A further aim was to select those lifestyle factors that would make it possible to predict the level of male fertility, especially when IR is concerned. Methods: This study was performed in a group of 73 participants, divided into groups based on their insulin resistance status. Their physical activity, diet, perceived stress, sleep quality, libido level, and duration of sexual abstinence were assessed on the basis of a number of parameters, including indices proposed by the authors. In addition, relevant anthropometric measurements were taken and tests related to glucose metabolism and semen quality were carried out. On the basis of these data, statistical tests were performed to establish or disprove relationships between lifestyle choices and semen quality, as measured my sperm motility. Results: The results of this study highlighted the associations between a number of parameters, i.e., micronutrient and vitamin intake, diet quality, body composition, insulin resistance, and the duration of sexual abstinence, and semen quality, as measured by sperm motility. Significantly, the presence or absence of IR was linked to male fertility. A multivariate model was developed, incorporating parameters such as the Matsuda index, vitamin intake, and sexual abstinence duration, to predict motility scores. Conclusions: This study underscores the negative impact of modern civilization's lifestyle choices on male fertility. Notably, vitamin and mineral consumption, especially from antioxidant-rich diets like the Mediterranean diet, emerged as key modifiable factors affecting fertility. Routine diagnostics for insulin resistance in fertility-related interventions is recommended. This study also highlights the importance of considering sexual abstinence duration during semen collection for accurate diagnostic results. Future research should focus on validating the proposed multivariate model and exploring the effects of lifestyle modifications, particularly vitamin supplementation, on fertility outcomes in men, especially in the context of IR.

Exploring protein relative relations in skeletal muscle proteomic analysis for insights into insulin resistance and type 2 diabetes.

The escalating prevalence of insulin resistance (IR) and type 2 diabetes mellitus (T2D) underscores the urgent need for improved early detection techniques and effective treatment strategies. In this context, our study presents a proteomic analysis of post-exercise skeletal muscle biopsies from individuals across a spectrum of glucose metabolism states: normal, prediabetes, and T2D. This enabled the identification of significant protein relationships indicative of each specific glycemic condition. Our investigation primarily leveraged the machine learning approach, employing the white-box algorithm relative evolutionary hierarchical analysis (REHA), to explore the impact of regulated, mixed mode exercise on skeletal muscle proteome in subjects with diverse glycemic status. This method aimed to advance the diagnosis of IR and T2D and elucidate the molecular pathways involved in its development and the response to exercise. Additionally, we used proteomics-specific statistical analysis to provide a comparative perspective, highlighting the nuanced differences identified by REHA. Validation of the REHA model with a comparable external dataset further demonstrated its efficacy in distinguishing between diverse proteomic profiles. Key metrics such as accuracy and the area under the ROC curve confirmed REHA's capability to uncover novel molecular pathways and significant protein interactions, offering fresh insights into the effects of exercise on IR and T2D pathophysiology of skeletal muscle. The visualizations not only underscored significant proteins and their interactions but also showcased decision trees that effectively differentiate between various glycemic states, thereby enhancing our understanding of the biomolecular landscape of T2D.

Assessment of smell disturbances 6 months after COVID-19 in Polish population.

Considering the frequency and severity of olfactory disorders associated with SARS-CoV-2 infection, attention to the olfactory loss has expanded. The aim of our study was to assess of smell disturbances 6 months after COVID-19. The study population consisted of 2 groups: 196 Post-COVID-19 patients who were hospitalized because of COVID-19, control sample-130 patients without reported smell disorders from general population-Bialystok PLUS study. People from both groups were asked to participate in the Sniffin Sticks Test (half year after the disease). Sniffin Sticks Test consisted of 12 standardized smell samples. The participant's test score was counted based on correct scent recognition. Middle/older age was related with lower likelihood of olfaction recovery. The biggest differences in recognition of particular fragrances were observed for: orange and lemon, lemon and coffee (p.adj < 0.001). Patients had the greatest problem in assessing smell of lemon. The comparison of scores between Delta, Omicron, Wild Type, Wild Type Alpha waves showed statistically significant difference between Delta and Wild Type waves (p = 0.006). Duration of the disease (r = 0.218), age (r = -0.253), IL-6 (r = -0.281) showed significant negative correlations with the score. Statistically significant variables in the case of smell disorders were Omicron wave (CI = 0.045-0.902; P = 0.046) and Wild Type wave (CI = 0.135-0.716; P = 0.007) compared to Delta wave reference. Moreover, patients with PLT count below 150 000/µl had greater olfactory disorders than those with PLT count over 150 000/µl. There are: smell differences between post-COVID-19 patients and healthy population; statistically significant difference between Delta and Wild Type waves in Post-COVID-19 group in score of the Sniffin Sticks Test. Smell disturbances depend on the age, cognitive impairments, clinical characteristics of the COVID-19 disease and sex of the patient.

Multi-ancestry polygenic mechanisms of type 2 diabetes.

Type 2 diabetes (T2D) is a multifactorial disease with substantial genetic risk, for which the underlying biological mechanisms are not fully understood. In this study, we identified multi-ancestry T2D genetic clusters by analyzing genetic data from diverse populations in 37 published T2D genome-wide association studies representing more than 1.4 million individuals. We implemented soft clustering with 650 T2D-associated genetic variants and 110 T2D-related traits, capturing known and novel T2D clusters with distinct cardiometabolic trait associations across two independent biobanks representing diverse genetic ancestral populations (African, n = 21,906; Admixed American, n = 14,410; East Asian, n =2,422; European, n = 90,093; and South Asian, n = 1,262). The 12 genetic clusters were enriched for specific single-cell regulatory regions. Several of the polygenic scores derived from the clusters differed in distribution among ancestry groups, including a significantly higher proportion of lipodystrophy-related polygenic risk in East Asian ancestry. T2D risk was equivalent at a body mass index (BMI) of 30 kg m-2 in the European subpopulation and 24.2 (22.9-25.5) kg m-2 in the East Asian subpopulation; after adjusting for cluster-specific genetic risk, the equivalent BMI threshold increased to 28.5 (27.1-30.0) kg m-2 in the East Asian group. Thus, these multi-ancestry T2D genetic clusters encompass a broader range of biological mechanisms and provide preliminary insights to explain ancestry-associated differences in T2D risk profiles.