Cancer stem cells (CSCs) represent a small but highly resilient tumor subpopulation responsible for sustained growth, metastasis, therapeutic resistance, and recurrence. Their survival is supported by aberrant activation of developmental and inflammatory pathways, including Wnt/β-catenin, Notch, Hedgehog, PI3K/Akt/mTOR, STAT3, and NF-κB, as well as epithelial–mesenchymal transition (EMT) programs and niche-driven cues. Increasing evidence shows that phytochemicals, naturally occurring bioactive compounds from medicinal plants, can disrupt these networks through multi-targeted mechanisms. This review synthesizes current findings on prominent phytochemicals such as curcumin, sulforaphane, resveratrol, EGCG, genistein, quercetin, parthenolide, berberine, and withaferin A. Collectively, these compounds suppress CSC self-renewal, reduce sphere-forming capacity, diminish ALDH⁺ and CD44⁺/CD24⁻ fractions, reverse EMT features, and interfere with key transcriptional regulators that maintain stemness. Many phytochemicals also sensitize CSCs to chemotherapeutic agents by downregulating drug-efflux transporters (e.g., ABCB1, ABCG2) and lowering survival thresholds, resulting in enhanced apoptosis and reduced tumor-initiating potential. This review further highlights the translational challenges associated with poor solubility, rapid metabolism, and limited bioavailability of free phytochemicals. Emerging nanotechnology-based delivery systems, including polymeric nanoparticles, lipid carriers, hybrid nanocapsules, and ligand-targeted formulations, show promise in improving stability, tumor accumulation, and CSC-specific targeting. These nanoformulations consistently enhance intracellular uptake and amplify anti-CSC effects in preclinical models. Overall, the consolidated evidence supports phytochemicals as potent modulators of CSC biology and underscores the need for optimized delivery strategies and evidence-based combination regimens to achieve meaningful clinical benefit.

Metabolic syndrome (MetS) is a complex metabolic disorder that includes central fat accumulation and insulin resistance, abnormal lipid levels, high blood pressure, and ongoing mild inflammation as its main symptoms. The global rise in metabolic syndrome parallels the increasing prevalence of male infertility, suggesting a potential association between metabolic health and reproductive function. Male fertility suffers from obesity, which represents a major element of metabolic syndrome because it disrupts hormonal balance, raises scrotal temperatures, and causes oxidative damage and HPG axis malfunction. Excess body fat functions as an endocrine system that induces the body to produce pro-inflammatory cytokines, which include tumor necrosis factor-α and interleukin-6, and various other inflammatory substances that result in ongoing body-wide inflammation. The state of inflammation leads to damaged spermatogenesis, which results in lower testosterone production and impaired semen quality that includes changes in sperm concentration, motility, morphology, and DNA integrity. The combination of insulin resistance and metabolic disturbances that occur in MetS leads to oxidative stress and mitochondrial dysfunction, which harms male reproductive abilities in testicular tissue. Recent research shows that adipokines and endocrine disruptors, together with epigenetic modifications, function as mediators that establish the connection between metabolic syndrome and male infertility. The development of targeted therapeutic strategies and lifestyle interventions requires researchers to study how obesity and chronic inflammation interact with each other to create reproductive dysfunction. This review defines the pathophysiological mechanisms that connect metabolic syndrome to male infertility by focusing on how obesity-related inflammation affects male reproductive health.

Background: Vitamin D deficiency is highly prevalent in patients with sickle cell disease (SCD) and may contribute to hematological dysregulation and increased vaso-occlusive crisis (VOC) burden. However, data from Sudan, a region with a substantial SCD burden, remain limited. This study investigated the prevalence and determinants of vitamin D deficiency and its association with hematological parameters and VOC frequency in Sudanese patients with SCD. Methods: A cross-sectional observational study was conducted among 50 patients with confirmed SCD attending a hematology outpatient clinic in Sudan. Serum 25-hydroxyvitamin D [25(OH)D] levels were measured using chemiluminescence immunoassay and categorized as deficient (<20 ng/mL), insufficient (20–29 ng/mL), or sufficient (≥30 ng/mL). Clinical and laboratory data, including hemoglobin concentration, annual VOC frequency, genotype, hydroxyurea use, hospitalization frequency, and sun exposure, were collected. Statistical analyses included chi-square tests, independent t-tests, Pearson correlation, and multivariable linear regression. Results: Vitamin D deficiency was identified in 54.0% of participants, whereas only 16.0% demonstrated sufficient vitamin D levels. Mean serum 25(OH)D concentration was 21.23 ± 7.44 ng/mL. HbSS patients exhibited significantly lower vitamin D levels compared with HbAS patients (19.89 ± 6.96 vs. 25.03 ± 7.71 ng/mL, p = 0.031). Serum 25(OH)D levels positively correlated with hemoglobin concentration (r = 0.584, p < 0.001) and inversely correlated with annual VOC frequency (r = −0.692, p < 0.001). Multivariable regression demonstrated that serum vitamin D was independently associated with hemoglobin levels (β = 0.048, p = 0.002) and annual VOC frequency (β = −0.121, p < 0.001) after adjustment for age, sex, genotype, sun exposure, and hydroxyurea use. Sun exposure was significantly associated with vitamin D status (p < 0.001). Conclusions: Vitamin D deficiency is highly prevalent among Sudanese patients with SCD and is significantly associated with anemia severity and increased VOC frequency. Given the single-center design and modest sample size, these findings should be regarded as exploratory and hypothesis-generating. They support routine vitamin D assessment and indicate that targeted supplementation strategies warrant evaluation as potential adjunctive approaches in SCD management in prospective, adequately powered studies.