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A Tepary bean lectin fraction (TBLF) has been studied because it exhibits differential cytotoxic and anticancer effects on colon cancer. The present work focuses on the evaluation of the apoptotic mechanism of action on colon cancer cells. Initially, lethal concentrations (LC50) were obtained for the three studied cell lines (HT-29, RKO and SW-480). HT-29 showed the highest LC50, 10 and 100 times higher than that of RKO and SW-480 cells, respectively. Apoptosis was evaluated by flow cytometry, where HT-29 cells showed the highest levels of early and total apoptosis, caspases activity was confirmed and necrosis was discarded. The effect on cell cycle arrest was shown in the G0/G1 phase. Specific apoptosis-related gene expression was determined, where an increase in p53 and a decrease in Bcl-2 were observed. Expression of p53 gene showed the maximum level at 8 h with an important decrease at 12 and 24 h, also the phosphorylated p53(ser46) increased at 8 h. Our results show that TBLF induces apoptosis in colon cancer cells by p-p53(ser46) involvement. Further studies will focus on studying the specific signal transduction pathway.

Pithecellobium dulce (P. dulce) is a Mexican plant that is consumed raw or in different preparations, and its anti-inflammatory and antioxidant properties have traditionally been useful in treating several conditions. However, the post-harvest drying process can alter the content of bioactive compounds in P. dulce. This study aims to evaluate the impact of different drying methods on the phenolic profile and antioxidant capacity of this plant, as well as its inhibitory effect on human SW480 colon adenocarcinoma cells. After oven drying, the samples showed a higher amount (p < 0.05) of phenolic compounds, up to 1149.45 ± 69.27 mg GAE/100 g LE, which is 80% more than the freeze-dried samples. Also, the antioxidant capacity was higher in oven-dried samples, with 44.63 ± 2.00 µmol Trolox equivalents/g LE, 108% more than the freeze-dried method. Methanolic extraction, in turn, yielded better results than aqueous and ethanolic extractions. Up to 14 polyphenolic compounds were detected in oven-dried samples. For in vitro assays in SW480 cells, the 50% v/v methanolic extract was used. From this extract, the median lethal concentration (LC50) was determined to be 13.76 mg/mL, which represents the concentration necessary to inhibit the growth of half of the cancer cells of this cell line. The extract led to cell cycle arrest in the G1 phase and an increase in apoptosis-induced cell death. The P. dulce extract augmented p53 and decreased KRAS gene expressions. Results suggested pro-apoptotic mechanisms in colon cancer cells in vitro linked to P. dulce bioactive compounds, which are better preserved when oven-dried plants are subjected to methanolic extraction.

Capsaicinoids are a unique chemical species resulting from a particular biosynthesis pathway of hot chilies (Capsicum spp.) that gives rise to 22 analogous compounds, all of which are TRPV1 agonists and, therefore, responsible for the pungency of Capsicum fruits. In addition to their human consumption, numerous ethnopharmacological uses of chili have emerged throughout history. Today, more than 25 years of basic research accredit a multifaceted bioactivity mainly to capsaicin, highlighting its antitumor properties mediated by cytotoxicity and immunological adjuvancy against at least 74 varieties of cancer, while non-cancer cells tend to have greater tolerance. However, despite the progress regarding the understanding of its mechanisms of action, the benefit and safety of capsaicinoids’ pharmacological use remain subjects of discussion, since capsaicin also promotes epithelial–mesenchymal transition, in an ambivalence that has been referred to as “the double-edge sword”. Here, we update the comparative discussion of relevant reports about capsaicinoids’ bioactivity in a plethora of experimental models of cancer in terms of selectivity, efficacy, and safety. Through an integration of the underlying mechanisms, as well as inherent aspects of cancer biology, we propose mechanistic models regarding the dichotomy of their effects. Finally, we discuss a selection of in vivo evidence concerning capsaicinoids’ immunomodulatory properties against cancer.

Introduction Insulin resistance (IR) is a key feature in the pathophysiology of metabolic disorders such as type 2 diabetes mellitus (T2DM) and obesity, both of which have a high prevalence in the Mexican population. Genetic predisposition plays a critical role in the development of IR, particularly through variants in carbohydrate metabolism genes. However, the specific contributions of these genetic factors in young Mexicans remain poorly characterized. Objectives This study aimed to identify associations between single nucleotide polymorphisms (SNPs) in carbohydrate metabolism-related genes and insulin resistance markers in a young Mexican population. Additionally, we sought to identify novel genetic variants that may contribute to metabolic risk and explore sex-specific genetic effects. Methods A genome-wide association study was conducted on 455 urban college students from Mexico. A total of 430 SNPs related to carbohydrate metabolism were genotyped. Clinical markers of IR, including fasting glucose, insulin, the homeostasis model assessment for insulin resistance (HOMA-IR), body mass index (BMI), body fat percentage (BF%), and waist circumference (WC), were evaluated. Associations between SNPs and metabolic traits were analyzed using logistic regression models adjusted for relevant covariates. Bonferroni correction was applied to account for multiple testing. Results Several SNPs were significantly associated with IR-related traits. SNPs in glucose metabolism genes, including GCK (rs1799884), SLC2 A9 (rs1122141), and IDH3B (rs6037255), were linked to fasting glucose levels, with IDH3B showing the strongest effect (OR 12.17, p  = 0.0144). Variants in insulin-related genes, such as SLC2 A9 , PFKP (rs3814591), and SLC45 A1 (rs12132135), were associated with elevated insulin and HOMA-IR. Adiposity-related SNPs, including those in PDK3 (rs7889665), PGK1 (rs2076630), and IDH2 (rs62019177), influenced body fat percentage and BMI. Notably, the novel variant rs77487659 (PGLS) was significantly associated with IR, particularly in women (OR 5.5, p  = 0.00005), highlighting a potential sex-specific effect. The SLC45 A1 variant rs12132135 demonstrated significant associations with multiple metabolic traits, including BMI, WC, and insulin resistance. Conclusion This study provides a comprehensive genetic analysis of IR-related traits in young Mexicans, highlighting both previously reported and novel associations. The findings suggest that genetic predisposition plays an important role in metabolic risk, with potential implications for early screening and personalized interventions. Sex-specific effects emphasize the need for tailored approaches in genetic risk assessment. Future research should focus on functional validation of these SNPs and their integration into precision medicine strategies for metabolic disease prevention.

Angiogenesis, the formation of new blood vessels, underlies tissue development and repair. Some medicinal plant-derived compounds can modulate the angiogenic response. Heliopsis longipes, a Mexican medicinal plant, is widely used because of its effects on pain and inflammation. The main bioactive phytochemicals from H. longipes roots are alkamides, where affinin is the most abundant. Scientific studies show various medical effects of organic extracts of H. longipes roots and affinin that share some molecular pathways with the angiogenesis process, with the vasodilation mechanism of action being the most recent. This study investigates whether pure affinin and the ethanolic extract from Heliopsis longipes roots (HLEE) promote angiogenesis. Using the aortic ring rat assay (ex vivo method) and the direct in vivo angiogenesis assay, where angioreactors were implanted in CD1 female mice, showed that affinin and the HLEE increased vascular growth in a dose-dependent manner in both bioassays. This is the first study showing the proangiogenic effect of H. longipes. Further studies should focus on the mechanism of action and its possible therapeutic use in diseases characterized by insufficient angiogenesis.

Snakebite envenoming is a serious medical problem in different areas of the world. In Latin America, the major prevalence is due to snakes of the family Viperidae, where rattlesnakes (Crotalus) are included. They produce hemotoxic venom which causes bleeding, tissue degradation and necrosis. Each venom has several enzymatic activities, producing different effects in the envenoming, doing its clinical effects difficult to study. Comparison between venom molecules is also difficult when different techniques are used, and therefore, their identification/characterization using the same methodology is necessary. In this work, a general biochemical characterization in snake venom of serine proteases (SVSP), phospholipases A2 (PLA2), metalloproteases (SVMP) and hyaluronidases (SVH) of Crotalus aquilus (Ca), Crotalus polystictus (Cp) and Crotalus molossus nigrescens (Cmn) was done. Differences in protein pattern, enzyme content and enzymatic activities were observed. All the venoms showed high PLA2 activity, high molecular weight SVSP, and a wide variety of SVMP and SVH forms. Ca and Cp showed the highest enzymatic activities of SVMP and SVSP trypsin-like and chymotrypsin-like, whereas Cmn showed the highest SVH and similar PLA2 activity with Ca. All the venoms showed peptides with similar molecular weight to crotamine-like myotoxins. No previous biochemical characterization of C. aquilus has been reported and there are no previous analyses that include these four protein families in these Crotalus venoms.

This study reviews the main candidate genes involved in the pathophysiology of Polycystic Ovary Syndrome (PCOS). PCOS is a common endocrine–metabolic disorder in women of reproductive age, characterized by menstrual irregularity, hyperandrogenism, and polycystic ovarian morphology. It is associated with increased metabolic and cardiovascular risk and is a leading cause of infertility. Although its pathophysiology is not fully understood, alterations in the hypothalamic–pituitary–ovarian axis, insulin metabolism, and steroidogenesis have been described. Polymorphisms in genes encoding hormones, enzymes, and receptors in these pathways contribute to clinical variability and ethnic differences, offering potential for early diagnosis and personalized medicine. This review summarizes key candidate genes related to insulin metabolism (INS, INSR, IRS-1), the hypothalamic–pituitary–ovarian axis (LHβ, LHCGR, FSHR, GnRHR, AMH, AMHR2, KISS1, CAPN10), steroidogenesis (CYP11A, CYP17A1, CYP19A1, CYP21, 17β-HSD, SHBG, AR, STAR), and other clinically relevant mechanisms such as obesity, lipid metabolism (PPARG, VDR, FTO), and follicular development (ACE).

Background: rTBL-1, a recombinant lectin from Phaseolus acutifolius, exhibit proapoptotic activity on colon cancer cells and inhibitory properties on colon tumorigenesis in vivo. Apoptosis has been associated with a phospho-EGFR/phospho-p38/phospho-p53 mechanistic axis. Immunogenicity data have been observed in treated animals, but its possible involvement in the antitumor response remained unexplored. Objective: We investigated whether the cytotoxic activity of rTBL-1 depends on EGFR and its capacity to produce antitumor responses on syngeneic colon cancer in mice, with and without T cells, in order to explore its possible involvement in the process. Results:rTBL-1 exhibited cytotoxic effects in a concentration-dependent manner in both EGFR+ (MC-38) and EGFR− (CT-26) colon cancer cells with LC50 values of 23.50 and 30.01 µg/mL, respectively (p = 0.063). Apoptotic effects were slower and longer-lasting in MC-38 than in CT-26 cells. Significant increases in caspase-3 proteolytic activation and PARP1 cleavage were detected in both cell types, despite PARP1 rheostasis in CT-26 cells. Intralesional treatment with rTBL-1 inhibited the growth of established tumors in immunocompetent BALB/c mice in 27.81% (p = 0.0008) with a benefit in survival (p = 0.022), but not in immunodeficient BALB/c nude mice. Conclusions:rTBL-1 induces apoptosis in colon cancer cells by EGFR independent mechanisms, although its presence could be related to deeper responses. Unresponsiveness in nude mice indicated that rTBL-1 antitumor effect is the synergistic result of apoptosis induction and T cell-mediated cytotoxicity in the tumor. Future studies will focus on the immunogenic effects triggered by the antitumor activity of rTBL-1 in colon cancer.

This study evaluated the immune response to a multiepitope recombinant chimeric protein (CHIVAX) containing B- and T-cell epitopes of the SARS-CoV-2 spike's receptor binding domain (RBD) in a translational porcine model for pre-clinical studies. We generated a multiepitope recombinant protein engineered to include six coding conserved epitopes from the RBD domain of the SARS-CoV-2 S protein. Pigs were divided into groups and immunized with different doses of the protein, with serum samples collected over time to determine antibody responses by indirect ELISA and antibody titration. Peptide recognition was also analyzed by Western blotting. A surrogate neutralization assay with recombinant ACE2 and RBDs was performed. Intranasal doses of the immunogen were also prepared and tested on Vietnamese minipigs. When the immunogen was administered subcutaneously, it induced specific IgG antibodies in pigs, and higher doses correlated with higher antibody levels. Antibodies from immunized pigs recognized individual peptides in the multiepitope vaccine and inhibited RBD-ACE2 binding for five variants of concern (VOC). Comparative antigen delivery methods showed that both, subcutaneous and combined subcutaneous/intranasal approaches, induced specific IgG and IgA antibodies, with the subcutaneous approach having superior neutralizing activity. CHIVAX elicited systemic immunity, evidenced by specific IgG antibodies in the serum, and local mucosal immunity, indicated by IgA antibodies in saliva, nasal, and bronchoalveolar lavage secretions. Importantly, these antibodies demonstrated neutralizing activity against SARS-CoV-2 . The elicited antibodies recognized individual epitopes on the chimeric protein and demonstrated the capacity to block RBD-ACE2 binding of the ancestral SARS-CoV-2 strain and four VOCs. The findings provide proof of concept for using multiepitope recombinant antigens and a combined immunization protocol to induce a neutralizing immune response against SARS-CoV-2 in the pig translational model for preclinical studies.

Previous works showed that a Tepary bean lectin fraction (TBLF) induced apoptosis on colon cancer cells and inhibited early colonic tumorigenesis. One Tepary bean (TB) lectin was expressed in Pichia pastoris (rTBL-1), exhibiting similarities to one native lectin, where its molecular structure and in silico recognition of cancer-type N-glycoconjugates were confirmed. This work aimed to determine whether rTBL-1 retained its bioactive properties and if its apoptotic effect was related to EGFR pathways by studying its cytotoxic effect on colon cancer cells. Similar apoptotic effects of rTBL-1 with respect to TBLF were observed for cleaved PARP-1 and caspase 3, and cell cycle G0/G1 arrest and decreased S phase were observed for both treatments. Apoptosis induction on SW-480 cells was confirmed by testing HA2X, p53 phosphorylation, nuclear fragmentation, and apoptotic bodies. rTBL-1 increased EGFR phosphorylation but also its degradation by the lysosomal route. Phospho-p38 increased in a concentration- and time-dependent manner, matching apoptotic markers, and STAT1 showed activation after rTBL-1 treatment. The results show that part of the rTBL-1 mechanism of action is related to p38 MAPK signaling. Future work will focus further on the target molecules of this recombinant lectin against colon cancer.