Background: In western Mexico, the Magnolia pacifica complex includes three morphologically defined, endemic and, endangered species, distributed along a 215 km continentality and moisture gradient: Magnolia pugana, M. pacifica s.s. , and M. vallartensis. Hypothesis: Genetic evidence supports the taxonomical classification of the M. pacifica complex. Study site and dates: Western Mexico, samples were collected in 2012-2015. Methods: Six Inter-Simple Sequence Repeats (ISSR) primers amplified 76 clear and reproducible fragments in 278 individuals from 10 localities representative of the M. pacifica complex. ISSR dataset was analyzed using STRUCTURE 2.3.4, UPGMA clustering, Barrier 2.2, and AMOVA. Genetic diversity parameters were also estimated. Results: Genetic analyses revealed two main groups: M. pugana and M. pacifica s.s.– M. vallartensis . Two subpopulations within each group were evidenced, particularly M. pacifica s.s. was separated from M. vallartensis . Geographical barriers to gene flow were identified. AMOVA revealed a similar and significant proportion of variation between and within groups. M. pugana has lower genetic diversity and higher differentiation than the M. pacifica s.s - M. vallartensis group. Conclusions: Our results support the recognition of M. pugana as a genetically distinct lineage from M. pacifica s.s and M. vallartensis , but did not reveal a clear species boundary between the last two taxa. Geographical barriers and distance isolation might explain the genetic structure and differentiation pattern within the M. pacifica s.s. species complex. All main groups and subgroups defined in this study should be considered as separate conservation units, and concerted efforts are needed to protect them.
Background: Androgen receptor mutations, particularly T877A and W741L, promote prostate cancer (PCa). The main therapies against PCa use androgen receptor (AR) antagonists, including Bicalutamide; but these drugs lose their effectiveness over time. Chrysin is a flavonoid with several biological activities, including antitumoral properties; however, its potential as an antiandrogen must be explored. Objective: The present study aimed to characterize and compare the molecular interactions of chrysin with wild-type and mutated ARs and their cytotoxic effect in an in vitro model of PCa. Methods: The affinities and molecular interactions of Bicalutamide and chrysin for the wild-type and mutated forms of AR were assessed by molecular docking. The MTT assay was used to evaluate the cytotoxic effect of these ligands on the DU-145 (T877A) and PC3 (W741L) PCa cell lines and on non-tumoral RWPE-1 cells. Results: The molecular dockings predicted a higher affinity of chrysin for the mutated AR than the wild-type AR (WT-AR); meanwhile, Bicalutamide presented a higher affinity for WT-AR. The amino acid residues involved in molecular interactions within the binding site of these receptors changed according to the ligands and AR variants, affecting their affinity scores. Chrysin exerted a specific cytotoxic effect against the PCa tumoral cells but none against the non-tumoral cells. In contrast, Bicalutamide showed potent cytotoxicity against all cell lines. Thus, the cytotoxic effect of chrysin against the DU-145 and PC3 cell line may be related to its strong and specific molecular interaction with the mutated ARs. Conclusion: This study evidences the potential antiandrogen effect of chrysin on mutated AR and specific cytotoxicity against PCa cells, suggesting that this flavonoid should be further studied in vivo to confirm its potential for therapy of advanced PCa.
Background: Several studies have shown that patients with cancer have antibodies in serum that react with cellular autoantigens, known as Tumor-Associated Antigens (TAA). The present work aimed to determine whether a mini-array comprising four recombinant TAA increases the detection of specific serum antibodies for the diagnosis of early-stage breast cancer. Methods: The mini-array included Alpha 1-AntiTrypsin (A1AT), TriosePhosphate Isomerase 1 (TPI1), Peptidyl-Prolyl cis-trans Isomerase A (PPIA), and PeroxiReDoXin 2 (PRDX2) full-length recombinant proteins. The proteins were produced after gene cloning, expression, and purification, and were verified by Western blot assays. Then, Dot-Blot was performed to find antibodies against the four TAA in 12 sera from women with early-stage breast cancer (stage II) and 12 sera from healthy women. Results: Antibody detection against individual TAA in early-stage breast cancer sera ranged from 58.3% to 83.3%. However, evaluation of the four TAA showed that there was a positive antibody reaction reaching a sensitivity of 100% and a specificity of 85% in early-stage breast cancer, suggesting that this mini-array must be evaluated as a clinical diagnostic tool for early-stage breast cancer in a larger sample size. Conclusion: Our results suggest that TAA mini-arrays may provide a promising and powerful method for improving the detection of breast cancer in Mexican women.
This study aimed to summarize the epidemiological and clinical characteristics of COVID-19 from Western Mexico people during 2020. A retrospective analysis from an electronic database of people visiting a sentinel center for molecular SARS-CoV-2 confirmatory diagnosis by RT-PCR from April to December 2020 was carried out for epidemiological and clinical description of COVID-19. Out of 23,211 patients evaluated, 6918 (29.8%) were confirmed for SARS-CoV-2 infection (mean age 38.5 ± 13.99), mostly females (53.8%). Comorbidities, such as diabetes (34.7%), obesity (31.15%), and hypertension (31.8%), presented an increased odds OR = 1.27, CI = 1.14–1.41; OR = 1.08, CI = 1.01–1.16; and OR = 1.09, CI = 0.99–1.19, respectively, for viral-infection. Moreover, fever, headache, and dry cough were the most frequent symptoms. No infection difference among sex was found. Those patients >60 years old were prone to COVID-19 severity (OR = 3.59, CI = 2.10–6.14), evaluated by the number of manifested symptoms, increasing with age. In conclusion, a high SARS-CoV-2 prevalence was found in Western Mexico. Comorbidities were frequent in infected people; nevertheless, no association with disease outcomes was observed, in contrast with the highest disease severity risk found in older patients; however, continuous monitoring should be carried since comorbidities have been reported as aggravating factors. This study can help the health officials for the elaboration of planning efforts of the disease management and others in the future.
Furin (Fur) is a member of the protease convertase family; its expression is crucial for cleaving and maturing many proteins. Fur also represents a therapeutic target in cancer, autoimmune diseases, and viral infections. Pioglitazone (PGZ) and rosiglitazone (RGZ) are thiazolidinediones prescribed to type 2 diabetes patients and are structurally similar to the known Fur inhibitors naphthofluorescein (NPF) and pirfenidone (PFD). Thus, this study used molecular docking and molecular dynamics to assess and compare the affinities and the molecular interactions of these four ligands with the Fur active site (FurAct) and the recently described Fur allosteric site (FurAll). The 7QXZ Fur structure was used for molecular dockings, and for the best pose complexes, molecular dynamics were run for 100 ns. The best affinities of the ligand/FurAct and ligand/FurAll complexes were with NPF, PGZ, and RGZ, while PFD presented the lowest affinity. Asp154 was the central residue involved in FurAct complex formation, while Glu488 and Asn310 were the central residues involved in FurAll complex formation. This study shows the potential of RGZ, PGZ, and PFD as Fur competitive (FurAct) and non-competitive (FurAll) inhibitors. Therefore, they are candidates for repurposing in response to future emerging diseases through the modulation of Fur activity.
Randia monantha, commonly known as crucetillo, is a medicinal plant traditionally used in Mexico to treat conditions such as diabetes, venomous animal bites, and cancer; however, its effects on cancer cell viability remain underexplored. In this study, hexane, ethyl acetate, and methanolic extracts from the leaves and fruits of Randia monantha were phytochemically characterized and evaluated for their effects on cell viability in HeLa cervical cancer and DU-145 prostate cancer cell lines using the MTT assay. Phytochemical analyses revealed differences in metabolite composition across solvents of varying polarity and plant tissues. Methanolic leaf extracts contained higher levels of terpenoids and polyphenols and produced the greatest reduction in HeLa cell viability, with an estimated IC50 of 4.87 µg/mL after 48 h of treatment. In contrast, DU-145 cells exhibited a different response pattern depending on the extract evaluated. Correlation analysis suggested that flavonoids were associated with reduced HeLa cell viability. Overall, leaf extracts produced greater reductions in cancer cell viability than fruit extracts, highlighting leaves as a promising but comparatively underexplored source of bioactive compounds in Randia monantha.