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Prostate cancer (PCa) is the most common cancer in men, accounting for approximately 10% of all new cases in the United States. Plant-derived bioactive compounds, such as pentacyclic triterpenoids (PTs), have the ability to inhibit PCa cell proliferation. We isolated and characterized nummularic acid (NA), a potent PT, as a major chemical constituent of Ipomoea batatas, a medicinal food plant used in ethnomedicine for centuries. In the current study, in vitro antiproliferative potential against PCa cells (DU145 and PC3) via 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay; Western blot protein expression analysis; absorption, distribution, metabolism, excretion (ADME); pharmacokinetic prediction studies; and bisphenol A (BPA)-induced prostate inhibition in Sprague Dawley rats were conducted to gauge the anti-cancer ability of NA. Significant (p < 0.05 and p < 0.01) time- and dose-dependent reductions in proliferation of PCa cells, reduced migration, invasion, and increased apoptotic cell population were recorded after NA treatment (3–50 µM). After 72 h of treatment, NA displayed significant IC50 of 21.18 ± 3.43 µM against DU145 and 24.21 ± 3.38 µM against PC3 cells in comparison to the controls cabazitaxel (9.56 ± 1.45 µM and 12.78 ± 2.67 µM) and doxorubicin (10.98 ± 2.71 µM and 15.97 ± 2.77 µM). Further deep mechanistic studies reveal that NA treatment considerably increased the cleavage of caspases and downstream PARP, upregulated BAX and P53, and downregulated BCL-2 and NF-κB, inducing apoptosis in PCa cells. Pharmacokinetic and ADME characterization indicate that NA has a favorable physicochemical nature, with high gastrointestinal absorption, low blood–brain barrier permeability, no hepatotoxicity, and cytochrome inhibition. BPA-induced perturbations of prostate glands in Sprague Dawley rats show a potential increase (0.478 ± 0.28 g) in prostate weight compared to the control (0.385 ± 0.13 g). Multi-dose treatment with NA (10 mg/kg) significantly reduced the prostate size (0.409 ± 0.21 g) in comparison to the control. NA-treated groups exhibited substantial restoration of hematological and histological parameters, reinstatement of serum hormones, and suppression of inflammatory markers. This multifaceted analysis suggests that NA, as a novel small molecule with a strong pharmacokinetic and pharmacological profile, has the potential to induce apoptosis and death in PCa cells. [ABSTRACT FROM AUTHOR]

Background: Pregnancy in patients with pulmonary hypertension (PH) is associated with a heightened risk of medical complications including right heart failure, pulmonary edema, and arrhythmias. Our study investigated the association between PH and these complications during delivery., Methods and Results: The National Inpatient Sample was used to identify delivery hospitalizations from 2011 to 2020. Multivariable logistic regression was performed to study the association of PH with the primary outcomes of in-hospital medical and obstetric complications. A total of 37 482 207 delivery hospitalizations in women ≥18 years of age were identified, of which 9593 patients had PH. Pregnant patients with PH had higher incidence of complications during delivery including preeclampsia/eclampsia, arrhythmias, and pulmonary edema among others, compared with those without PH. Pregnant patients with PH also had a higher incidence of in-hospital mortality compared with those without PH (0.51% versus 0.007%). In propensity-matched analyses, PH was still significantly associated with a higher risk of in-hospital mortality (odds ratio [OR], 5.02 [95% CI, 1.82-13.90]; P =0.001), pulmonary edema (OR, 9.11 [95% CI, 6.34-13.10]; P <0.001), peripartum cardiomyopathy (OR, 1.85 [95% CI, 1.37-2.50]; P <0.001), venous thromboembolism (OR, 12.60 [95% CI, 6.04-26.10]; P <0.001), cardiac arrhythmias (OR, 6.11 [95% CI, 4.97-7.53]; P <0.001), acute kidney injury (OR, 3.72 [95% CI, 2.86-4.84]; P <0.001), preeclampsia/eclampsia (OR, 2.24 [95% CI, 1.95-2.58]; P <0.001), and acute coronary syndrome (OR, 2.01 [95% CI, 1.06-3.80]; P =0.03), compared with pregnant patients without PH., Conclusions: Delivery hospitalizations in patients with PH are associated with a high risk of mortality, pulmonary edema, peripartum cardiomyopathy, venous thromboembolism, arrhythmias, acute kidney injury, preeclampsia/eclampsia, and acute coronary syndrome.

In this retrospective study, spanning from 1999 to 2020, we examined mortality trends related to SICM (substance-induced cardiomyopathy) among individuals aged 75 and older. A total of 473,408 SICM-related deaths were identified, with detailed data on the place of death available for 454,632 cases, revealing that a significant proportion occurred in medical facilities (45.43 %), nursing homes (24.67 %), hospices (4.21 %), and at home (25.69 %). Our analysis of age-adjusted mortality rates (AAMR) showed an overall decline from 1999 to 2020, decreasing from 14.5 to 7.7 per 10,000 population, with an initial increase from 1999 to 2001 followed by a subsequent decline. Gender-based analysis indicated consistently higher AAMRs for elderly men compared to elderly women. Moreover, we observed variations in AAMRs based on race and ethnicity, with NH Black or African American individuals having the highest AAMRs. Geographic disparities were notable, with states like Delaware having AAMRs twice as high as Utah. The Southern region consistently exhibited the highest AAMR, followed by the Midwestern, Northeastern, and Western regions. Furthermore, metropolitan areas consistently had higher AAMRs than nonmetropolitan areas, although both showed declining trends over the study period. These findings provide valuable insights into SICM-related mortality patterns among the elderly population, emphasizing the importance of considering demographic and geographic factors in public health planning and interventions., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)