Mario A. Alcalá-Pérez

Background/Objectives: Lung cancer exhibits substantial international variation in incidence that cannot be fully explained by established individual-level risk factors alone. Although tobacco smoking remains the principal cause of lung cancer, international ecological associations may also be influenced by differences in socioeconomic development, epidemiological transition, healthcare infrastructure, diagnostic capacity, and cancer registration systems. This study examined country-level associations between behavioral, environmental, occupational, dietary, metabolic, socioeconomic, and healthcare indicators and lung cancer incidence across 183 countries. Methods: An ecological cross-sectional study was conducted across 183 countries. Lung cancer incidence estimates for 2024 were obtained from the International Agency for Research on Cancer (IARC) Global Cancer Observatory, Cancer Today platform, using GLOBOCAN 2024. Exposure and contextual indicators were obtained from international databases, with reference years varying across indicators. Incidence was evaluated for the total population, males, females, and individuals aged 15–64 years. Country-level associations were assessed using exploratory Spearman correlations, exploratory receiver operating characteristic (ROC) analyses, and multivariable linear regression models. Analytical sample sizes varied according to data availability. Results: Indicators associated with socioeconomic development, including expected years of schooling (ρ = 0.664–0.728), personal health expenditure (ρ = 0.656–0.706), meat consumption (ρ = 0.640–0.732), and tobacco consumption (ρ = 0.492–0.677), showed consistent positive ecological associations with lung cancer incidence. Occupational silica exposure showed small positive ecological correlations (ρ = 0.194–0.278). Conversely, unsafe water sources (ρ = −0.729 to −0.786) and unsafe sanitation (ρ = −0.661 to −0.763) exhibited strong inverse ecological associations. Multivariable regression models explained 55.4–66.1% of the international variability in lung cancer incidence, with tobacco consumption showing positive associations across all demographic groups after adjustment for the other covariates included in the models. The inverse ecological associations observed for unsafe water and sanitation indicators may reflect differences in socioeconomic development, epidemiological transition, diagnostic capacity, and cancer registration systems; however, these explanations were not directly evaluated and should not be interpreted as evidence of biologically protective effects. Conclusions: Selected country-level indicators were associated with international variation in lung cancer incidence. Tobacco consumption showed positive associations across all demographic groups after adjustment for the covariates included in the models. The inverse ecological associations observed for unsafe water and sanitation indicators may reflect contextual differences between countries, but these explanations were not directly evaluated. The findings remain susceptible to residual confounding and do not establish individual-level causal relationships.

Background/Objectives: Orally administered herbal preparations have gained attention as complementary approaches in supportive cancer care; however, their clinical efficacy and safety remain uncertain. This systematic review critically evaluated evidence from randomized clinical trials investigating these interventions in patients with cancer. Methods: The review followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines and was prospectively registered in PROSPERO. PubMed/MEDLINE, ScienceDirect, Springer Nature Link, CENTRAL, Scopus, LILACS, ClinicalTrials.gov, and WHO ICTRP were searched for English-language studies published from January 1990 through 8 September 2026. Risk of bias was assessed using RoB 2, and outcome-level certainty was evaluated using GRADE. Results: Eight randomized clinical trials met the eligibility criteria and were included in the qualitative synthesis. The studies evaluated Gamiguibi-tang, Rikkunshito, holy basil (Ocimum tenuiflorum), Alcea digitata–Malva sylvestris, Annona muricata, Malva sylvestris–Althaea digitata, Jing Si herbal tea, and Renshen Yangrong Tang across heterogeneous cancer populations. Individual trials reported potentially favorable findings for sleep, fatigue, chemotherapy-induced anorexia, anxiety, salivary function, xerostomia, gastrointestinal symptoms, and quality of life. However, the Jing Si herbal tea trial found no statistically significant between-group differences in fatigue or quality of life, and exploratory ex vivo cytotoxicity findings did not demonstrate clinical antitumor efficacy. Meta-analysis was not feasible because of substantial clinical and methodological heterogeneity. All evaluated outcomes were rated as very-low-certainty evidence, primarily because of risk of bias and serious imprecision. No serious intervention-related adverse events were identified in the published reports, but adverse-event monitoring was inconsistent and no trial was adequately powered to establish safety. Conclusions: The available evidence is insufficient to establish definitive efficacy or safety or to support routine clinical implementation. Adequately powered multicenter trials using botanically authenticated and chemically characterized preparations, clinically meaningful outcomes, interaction assessment, and long-term pharmacovigilance are required.

Background/Objectives: Acute collective emotional events may coincide with variation across multiple dimensions of mental health and health-related behaviors. This study compared mental health outcomes and recent alcohol consumption between assessments conducted before and after a major international sporting event and explored factors associated with psychological and behavioral outcomes among young adults. Methods: An observational study was conducted among 146 adult students in western Mexico who participated in assessments surrounding the 2026 FIFA World Cup match between Mexico and England. Assessments were conducted approximately 10 h before kick-off and 11 h after completion of the match. Because individual responses could not be linked across assessment periods, comparisons were analyzed as repeated cross-sectional marginal comparisons rather than paired longitudinal analyses. Psychological outcomes were assessed using standardized instruments, and recent alcohol consumption was defined as alcohol use during the eight hours preceding each assessment. Results: Anxiety-related symptom scores were lower at the post-event assessment, whereas depressive-related symptoms remained relatively stable. Emotional well-being was also lower at the post-event assessment, while recent alcohol consumption during the eight hours preceding the assessment was substantially more frequent post-event than pre-event (41.1% vs. 0.7%). The small difference observed in sexual-attitude scores was considered exploratory. Post-event multivariable analyses identified several factors associated with psychological outcomes and recent alcohol consumption; these associations were interpreted as cross-sectional. Conclusions: Psychological and behavioral outcomes exhibited distinct patterns between assessment periods surrounding the sporting event. Given the observational design, inability to link individual responses, and presence of unmeasured co-occurring exposures, these differences should not be interpreted as within-participant changes or as effects attributable specifically to the match.

Background/Objectives: Herbal medicine is one of the most widely used forms of complementary medicine worldwide. Although traditionally associated with rural populations and older generations, its use among urban adolescents and young adults and the factors associated with its use remain insufficiently understood. This study aimed to evaluate herbal medicine knowledge, use, recommendation practices, and their associations with family-based recommendation, social media exposure, and previous experience using herbal medicine together with conventional medical treatment among urban adolescents and young adults in western Mexico. Methods: A cross-sectional study was conducted among 144 urban high school students in western Mexico. A structured questionnaire was used to assess sociodemographic characteristics, herbal medicine knowledge, use, recommendation practices, family-based recommendation, social media exposure, and self-reported concurrent use with conventional medical treatment. Bivariate and multivariable logistic regression analyses were performed to identify factors independently associated with herbal medicine use, recommendation, and self-reported knowledge. Results: Herbal medicine use was reported by 36.8% of participants, whereas 31.9% reported knowing what herbal medicine is. Family-based recommendation was independently associated with herbal medicine use (OR = 8.04; 95% CI: 2.99–21.61; p < 0.001), followed by self-reported herbal medicine knowledge (OR = 4.56; 95% CI: 1.97–10.58; p < 0.001). Recommendation behavior was independently associated with family-based recommendation (OR = 3.70; 95% CI: 1.45–9.44; p = 0.006) and previous herbal medicine use (OR = 4.16; 95% CI: 1.75–9.93; p = 0.001). Among herbal medicine users, all participants reported previous experience using herbal medicine together with conventional medical treatment, suggesting the coexistence of both therapeutic approaches within this study population. Social media exposure was associated with self-reported herbal medicine knowledge (OR = 2.97; 95% CI: 1.06–8.27; p = 0.038) but was not associated with herbal medicine use or recommendation. Conclusions: Among this study population, herbal medicine was commonly reported and appeared to be part of complementary healthcare practices among urban adolescents and young adults. Family-based recommendation was independently associated with herbal medicine use and recommendation, whereas social media exposure was associated primarily with self-reported knowledge rather than behavioral outcomes. These findings highlight the importance of considering herbal medicine use during clinical communication and adolescent health education while recognizing the coexistence of herbal and conventional healthcare practices.

Background/Objectives: Improper medication use, premature treatment discontinuation, and inadequate disposal contribute to irrational drug consumption and environmental contamination. Although pharmaceutical take-back programs have expanded globally, real-world evidence on household medication accumulation in academic and community settings remains limited. This study aimed to describe longitudinal patterns of medication collection during an eleven-year university-based take-back campaign, with detailed pharmacological characterization available for selected post-pandemic years. Methods: Real-world data were analyzed from a sustainable medication take-back campaign conducted annually at the University of Colima between 2015 and 2025. Expired or unused medications were voluntarily returned by students and community members. Total collected weight was recorded for all years, while detailed classification by dosage form, Anatomical Therapeutic Chemical (ATC) group, and Mexican regulatory fraction (Fractions II, IV, V, and VI) was performed for years with complete records (2023–2025). All materials were disposed of through an authorized hazardous-waste company in compliance with NOM-052-SEMARNAT-2005. Descriptive analyses were performed using SPSS version 29.0. Results: Approximately 3.9 tons of pharmaceutical products were collected over eleven years, reflecting persistent household accumulation of unused or expired medicines. In the years with detailed analysis, oral solid dosage forms predominated. In 2025, ATC groups M, A, and C were most frequently returned, consistent with medications used for chronic conditions. Therapeutic composition varied annually, with NSAIDs/analgesics predominating in 2023–2024 and antibiotics in 2025. Across analyzed years, 5–7% of collected items corresponded to non-medication products. Conclusions: This long-term campaign provides valuable real-world evidence on medication non-use and disposal, highlighting ongoing challenges in rational medicine use, treatment continuity, and environmentally responsible pharmaceutical waste management.

The widespread use of glyphosate-based herbicides (GBHs) has raised concerns about their potential role in hormone-sensitive cancers such as breast cancer. This systematic review aimed to evaluate preclinical evidence on the effects of glyphosate (pure compound) or glyphosate-based herbicide formulations (GBHs) exposure on breast cancer cell proliferation and related molecular pathways. A structured search was conducted across PubMed, ScienceDirect, and Springer Nature Link, Web of Science databases, covering studies published up to 9 November 2025, following a PROSPERO-registered protocol (ID: CRD42021238350). Eligible studies included original in vitro and in vivo preclinical research using human breast cancer cell lines (e.g., MCF-7, T47D, MDA-MB-231, MCF-12A, and MCF-10A) or relevant animal models. Outcomes assessed included cell viability, proliferation, tumor growth, apoptosis, cell cycle regulation, and molecular markers associated with endocrine signaling. Two reviewers independently screened and extracted data, resolving disagreements via discussion or third-party adjudication. From an initial pool of 699 articles, seven in vitro studies met the inclusion and quality criteria. Glyphosate exposure demonstrated weak estrogenic activity in ER-positive breast cancer cells, primarily via ERα modulation and altered gene expression related to proliferation and DNA repair. GBHs showed greater cytotoxic and epigenetic effects in non-tumorigenic cells, often independent of ER signaling. No included study employed in vivo breast cancer models. Overall, preclinical evidence suggests glyphosate may act as a weak endocrine disruptor under specific conditions, but findings are limited by the short-term in vitro designs, heterogeneous methodologies, and lack of chronic or in vivo data. Further research using long-term exposure and animal models is needed to clarify potential risks and inform regulatory and public health decisions.

Breast cancer remains a leading cause of global cancer burden, with marked differences in incidence across countries. While biological risk factors are well established, understanding the broader structural and sociocultural influences has been less comprehensive. In this study, we analyzed harmonized data from 183 countries (2017–2023), encompassing 33 variables and 7 subvariables related to demographics, nutrition, environment, health, and healthcare access, drawn from open-access international databases. Spearman correlation analysis identified strong positive associations between breast cancer incidence and discontinued breastfeeding, high LDL cholesterol, out-of-pocket healthcare expenditure, and educational attainment. Conversely, poor sanitation, lack of handwashing facilities, unsafe water, and certain nutritional deficiencies exhibited robust negative correlations, likely reflecting under detection and reporting limitations in lower-resource settings rather than true protective effects. These findings were further explored using multiple linear regression, which explained approximately 73% of the variance in global breast cancer incidence. The final model highlighted discontinued breastfeeding, prevalence of cocaine use, unsafe sanitation, high out-of-pocket healthcare expenditure, limited handwashing access, and high processed meat consumption as the most influential independent predictors. Receiver operating characteristic (ROC) analysis confirmed strong predictive value for discontinued breastfeeding and out-of-pocket expenditure, with sanitation and hygiene variables showing paradoxical inverse associations. Our results emphasize that breast cancer risk is shaped not only by individual behaviors and genetics, but also by larger-scale structural, socioeconomic, and environmental factors. These patterns suggest that targeted interventions addressing both lifestyle behaviors and systemic inequities—such as promoting breastfeeding, reducing financial barriers to healthcare, and strengthening public health infrastructure—could meaningfully reduce the global burden of breast cancer. In conclusion, this study underscores the importance of multisectoral, equity-focused prevention strategies. It also highlights the value of country-level ecological analyses in uncovering upstream determinants of cancer incidence and calls for further research to disentangle individual and contextual effects in cancer epidemiology.

Background/Objectives: Annona muricata (AM), commonly known as soursop or guanabana, has long been used in traditional medicine for its purported anticancer properties. However, scientific studies evaluating its potential enhancing or additive effects with conventional antineoplastic drugs (ADs) remain limited. This study aimed to assess the cytotoxic effects of an aqueous AM infusion alone and in combination with standard ADs in cancer cell lines, while also evaluating its safety in healthy cells. Additionally, we explored the potential molecular interactions of AM metabolites with therapeutic targets using silico modeling. Methods: An AM infusion (125 and 250 µg/mL) was tested on two cancer cell lines—MDA-MB-231 (human triple-negative breast cancer) and TC-1 (murine HPV16-positive cancer)—as well as healthy human leukocytes and a non-tumorigenic mouse lung cell line. Cell viability was assessed using the Alamar Blue™ assay. The combined effects of AM with multiple first-line ADs were evaluated. In silico molecular docking was performed with Molegro Virtual Docker to assess the interaction of AM metabolites (quercetin and hyperoside) with the A2B adenosine receptor. Additionally, the physicochemical properties of 13 AD were analyzed to explore correlations with cytotoxic outcomes. Results: AM infusion alone exhibited low cytotoxicity in both cancer and healthy cell types. However, when combined with ADs, it enhanced cytotoxic effects in cancer cells while sparing healthy cells at the evaluated concentrations. Docking studies revealed strong interactions between quercetin and hyperoside (major metabolites in the AM infusion) and the A2B receptor, supporting a possible mechanistic explanation for the observed effects. Conclusions: AM infusion may act as a chemical modulator, potentiating the effects of conventional ADs in cancer cells while preserving normal cell viability. These findings encourage further preclinical exploration of AM as a complementary agent in integrative oncology.

Background: Annona muricata L. (guanabana) leaves are rich in bioactive compounds with potential antioxidant properties. In the state of Colima, both ethanolic extracts and infusions are traditionally used in folk medicine to address various ailments. This study aimed to evaluate and compare the phytochemical composition and antioxidant activities of ethanolic extracts and infusions of A. muricata leaves from three geographic regions in Colima, Mexico, with a focus on how geographic origin affects their bioactive properties. Methods: Ethanolic extracts and infusions were prepared from A. muricata leaves and analyzed using phytochemical screening; DPPH, total antioxidant capacity (TAC), and total phenolic content (TPC) measurements; and HPLC. TLC was also conducted to examine the presence of specific compounds, such as flavonoids and phenols. Results: Both the ethanolic extracts and infusions contained significant levels of alkaloids, flavonoids, tannins, and phenolic compounds. The infusions demonstrated superior antioxidant capacity, with DPPH inhibition values of 72.5%, 68.3%, and 65.1% in the northern, central, and southern regions, respectively, compared to the ethanolic extracts’ values of 50.3%, 48.9%, and 45.0%. HPLC identified quercetin as a major compound across all samples. Geographically, the northern region exhibited higher concentrations of bioactive compounds, particularly total flavonoid content (TFC) and iron-reducing power (FRPA). Conclusions: Both the ethanolic extracts and infusions of A. muricata leaves exhibited significant antioxidant properties, with the infusions showing superior performance. The results suggest that A. muricata infusions may have potential applications in managing oxidative stress-related diseases such as cancer and diabetes. Exploring their use in traditional medicine and employing this type of approach can help discern the metabolite profile responsible for these bioactivities. Geographic factors influence the bioactive profile of the plant, and further research is needed to isolate specific bioactive compounds and elucidate their therapeutic mechanisms.

Salvia officinalis (SO) is one of the most widely used plants in traditional medicine worldwide. In the present study, the effect of an ethanolic extract of S. officinalis leaves on hallmarks of cancer of HPV-16-positive cancer tumorigenic cells, TC-1, was analyzed in vitro. Phytochemical and spectroscopic analysis were performed. Additionally, the extract’s flavonoid content, reducing iron, and antioxidant capacity were determined. In regard to the in vitro tests, the cytotoxic activity and its effect on the replicative capacity and on the cell migration of TC-1 cells were analyzed by viability and clonogenic, survival, and wound healing assays. The effect of a pre-treatment or treatment on 3D culture formation, growth, and reversion capacity was also examined. The results of the phytochemical analysis allowed the detection of tannins, saponins, steroids, and flavonoids. The flavonoids content was found to be 153.40 ± 10.68 µg/mg of extract. Additionally, the extract exhibited an antioxidant capacity and a ferric-reducing capacity of around 40% compared to the ascorbic acid. Thin layer chromatographic (TLC) analysis and spectroscopic tests showed the presence of compounds similar to quercetin and catechin flavonoids in the extract. In the in vitro assays, the SO extract induced in a concentration-dependent way changes in cell morphology, the decrease of cell viability, survival, and migration. At a concentration of 125 µg/mL, the extract inhibited spheroid formation, reduced their growth, and affected their reversion to 2D. Ethanolic extract of S. officinalis leaves had inhibitory effects on hallmarks of the cancer line HPV-16+. This suggests that the phytochemicals present in it may be a source of chemotherapeutics against cervical cancer.