Furofuranone Lignans from Leucophyllum ambiguum Rios, María Y; Ocampo-Acuña, Yordin D; Ramírez-Cisneros, M. Ángeles ...
Journal of natural products (Washington, D.C.),
05/2020, Letnik:
83, Številka:
5
Journal Article
Recenzirano
Eight furofuranone lignans with an endo,endo relationship between the oxygen atoms, an exo,exo relationship between the aryl groups, and a chair,chair conformation (1–4 and 6–9), in addition to the ...α-amino acid (3S)-hydroxy-3′,4′-dimethoxy-L-phenylalanine (5), veratric acid (10), and β-sitosterol (11), were isolated from the powdered and defatted air-dried aerial parts of Leucophyllum ambiguum. Four of these lignans, ciquitins A–D, 1–4, were isolated for the first time as natural products. The structures of these compounds were established based on their spectrometric/spectroscopic data. Additionally, single-crystal X-ray crystallography confirmed the structure of ciquitin A (1), and derivatization with (9S)-naproxen and X-ray diffraction crystallography data established its absolute configuration. Ciquitins A (1) and B (2) possess a 9-hydroxy group; this chemical characteristic grants these species conformational isomerism not seen in the other six lignans. The conformers of 1 and 2 are distinguishable via their 1H and 13C NMR spectroscopic data. This is the first report of this phenomenon, and hence, a complete assignment of the signals in both spectra of each conformer for each compound is presented. Compounds 1–9 were found to exhibit potent inhibitory activity in the 1.0 × 10–3 to 2.2 μM range against acetylcholinesterase, an enzyme directly involved in the etiology of Alzheimer’s disease and senile dementia. Thus, these natural products are promising agents that are potentially useful for the treatment of neurological degeneration.
Current medical guidelines consider pregnant women with COVID-19 to be a high-risk group. Since physiological gestation downregulates the immunological response to maintain “maternal-fetal ...tolerance”, SARS-CoV-2 infection may constitute a potentially threatening condition to both the mother and the fetus. To establish the immune profile in pregnant COVID-19+ patients, a cross-sectional study was conducted. Pregnant women with COVID-19 (P-COVID-19+; n = 15) were analyzed and compared with nonpregnant women with COVID-19 (NP-COVID-19+; n = 15) or those with physiological pregnancy (P-COVID-19-; n = 13). Serological cytokine and chemokine concentrations, leucocyte immunophenotypes, and mononuclear leucocyte responses to polyclonal stimuli were analyzed in all groups. Higher concentrations of serological TNF-α, IL-6, MIP1b and IL-4 were observed within the P-COVID-19+ group, while cytokines and chemokines secreted by peripheral leucocytes in response to LPS, IL-6 or PMA-ionomicin were similar among the groups. Immunophenotype analysis showed a lower percentage of HLA-DR+ monocytes in P-COVID-19+ than in P-COVID-19- and a higher percentage of CD39+ monocytes in P-COVID-19+ than in NP-COVID-19+. After whole blood polyclonal stimulation, similar percentages of T cells and TNF+ monocytes between groups were observed. Our results suggest that P-COVID-19+ elicits a strong inflammatory response similar to NP-COVID19+ but also displays an anti-inflammatory response that controls the ATP/adenosine balance and prevents hyperinflammatory damage in COVID-19.
Objectives: In many cases, the socioeconomic status of patients diagnosed with metastatic renal cell carcinoma (mRCC) in developing countries could limit their access to the best available ...therapeutic options. We aimed to describe the clinical characteristics and access to treatment of Mexican patients with mRCC. Materials and methods: We performed a retrospective analysis of all patients with a histopathologically confirmed diagnosis of renal cell carcinoma treated at an oncology referral center in Northeast Mexico over a 5-year period. Results: We included 233 patients in the analysis, of whom 63% were men. The mean age at diagnosis was 58.2 years; 87% of the tumors were histopathologically classified as clear cell carcinoma. Regarding laterality, 54% of the tumors originated from the right kidney. The distribution of cases by clinical stage (CS) was as follows: CS I 15%, CS II 8%, CS III 17%, and CS IV 60%. In terms of access to first-line systemic management in the 139 patients with advanced kidney cancer who were candidates for treatment, 29% received treatment with a single-drug tyrosine kinase inhibitor (TKI), 4% were treated with combined or single-drug immunotherapy (IO), and 12% were treated with TKI combined with IO. Fifty-five percentages of patients with the advanced disease did not have access to standard first-line therapy, and the rate of loss to medical follow-up was 69% of cases. Conclusions: Despite the proven oncological benefit of the latest generation of therapies based on IO/IO or IO/TKI for mRCC, access to first-line standard management is still poor in our country.
A case-control study was carried out in Mexico City during 1995-1997 among women with epithelial ovarian cancer (84 cases) and endometrial cancer (85 cases). The control group consisted of 668 ...healthy women, matched according to age categories. In a multivariate analysis, the reproductive risk factors for ovarian and endometrial cancer are similar. The risk of ovarian cancer was inversely related to the number of full-term pregnancies; the odds ratio (OR) was 0.17 and the 95% confidence interval (CI) was 0.05-0.54 when comparing nulliparous women versus those with more than seven pregnancies. For endometrial cancer, a similar association was observed (OR, 0.11; 95% CI, 0.04-0.34). The use of oral contraceptive hormones was inversely associated with both ovarian (OR, 0.36; 95% CI, 0.15-0.83) and endometrial cancer risk (OR, 0.36; 95% CI, 0.14-0.90). In women with a history of more than 8.7 years without ovulation, the risk of ovarian cancer decreased four times (OR, 0.23; 95% CI, 0.10-0.50), and that of endometrial cancer decreased more than five times (OR, 0.17; 95% CI, 0.08-0.35). These two neoplasms are clearly typified as hormone dependent, and it is possible to establish that "ovulation" and "exfoliative" mechanisms jointly determine the level of risk for both ovarian and endometrial cancer.
Daily diet factors that could potentially be related to endometrial cancer (EC) in Mexico are still unknown. This study aims to evaluate the association between EC and Mexican dietary factors. A ...case-control study in Mexico City was conducted during 1995-1997 in a social security hospital, using 85 incident cases of EC and 629 controls. A validated questionnaire with 116 items about the frequency and type of food intake was used. The analysis of nutrients was performed using the residual method, adjusting by predictor variables through logistic regression methods. In addition, partitional models estimated total caloric intake for other sources. We found no association between EC risk and consumption of animal or vegetable proteins, saturated, monounsaturated, or polyunsaturated fat, although high intake of nutrients such as lactose (odds ratio OR, 0.46; 95% confidence interval CI, 0.21-1.01, P for trend = 0.004), vitamin D (OR, 0.38; 95% CI, 0.18-0.82, P= 0.003), and calcium (OR, 0.39; 95% CI, 0.17-0.89, P= 0.02) were inversely associated with EC. Our results suggest that dietary vitamin D and calcium play an important role in the development of EC, although the mechanisms postulated should be explained with additional studies with large populations.
The inland waters of Chile hold endemic species of crustaceans, and these habitats are threatened at present due to pollution as a result of human activities. Until now, the environmental studies ...performed have not considered native species for evaluating environmental risks. The aim of the present study was to do a first culture experiment with the freshwater copepod Tumeodiaoptomus diabolicus that inhabits central and northern Chilean Patagonian lakes. The copepods were cultured under two dietary regimes, i.e., a diet of microalgae and an artificial diet. The experiment was conducted over 12 days, and the maximum growth was obtained with the artificial diet. The present results would agree with similar results obtained for pseudodiaptomid copepods, that are massively used for aquaculture activities. In accordance with the obtained results and published data in the literature, T. diabolicus culture could be relatively easily done, and would thus qualify as an assay for investigating environmental conditions.
The purpose of this study was to identify risk factors associated with the development of non-epithelial ovarian cancer in Mexican women. A case-control study was carried out on women registered with ...the Mexican Institute of Social Security in Mexico City over a period of two years (1995-97). Twenty-eight new cases were recruited from the Gynecology and Obstetrics Hospital no. 4, "Luis Castelazo Ayala", and were matched by age with 84 controls selected randomly. Eighteen (64.3%) cases of germ cell tumors and 10 (35.7%) stromal sex cord tumors were found. The number of full term pregnancies was associated inversely to development of stromal sex cord tumors with lower risk in women with more than three full term pregnancies (odds ratio, 0.02: 95% confidence interval, 0.001-0.56) compared to nulliparous women. No associations were found respecting to germ cell tumors. Parity was inversely associated to development of stromal sex cord tumors, probably as a result of the endocrine system's influence on the ovaries. The development of germ cell tumors could be associated to factors not evaluated in this study.
Background:
The Chlorambucil‐Obinutuzumab (CI‐O) is a therapeutic regimen for unfit patients with chronic lymphocytic leukemia (CLL), whether due to old age or with comorbidities that keep them from ...receiving intensive chemotherapeutic treatment. Results of the CLL11 clinical trial position this treatment as a first‐line alternative with 1A category because of its safety and efficacy among these patient.
Aims:
To analyze our real‐life experience in terms of safety and effectiveness in first‐line treatment with the CI‐O combination in elderly or unfit patients with CLL.
Methods:
This retrospective study included 69 unfit CLL patients from 12 hospitals from the GRANEL group (Andalusia, Spain) with first‐line treatment out of clinical trial from May 2016 to February 2019 following a CI‐O protocol. Before treatment, patients were assessed using the comorbidities scale CIRS (Cumulative Illness Rating Scale score). Demographic data, illness, complications, and responses to treatment are analyzed.
Results:
Baseline features are shown in table 1. At the time of analysis, 9 out of 69 patients of the series are still in treatment. From the remaining 60, 48 (80%) completed 6 programmed cycles, 2 (3.3.%) received 5 cycles, 3 (5%) received 4 cycles, 2 (3.3%) received 3 cycles and 5 (8.3%) only 1 cycle (2 deaths after the first cycle, 1 infusion reaction that led to ceasing treatment, 1 progression and later second‐line and a decision to stop treatment by the medical team due to stable illness after cycle 1). 69.6% of patients received treatment without infusion reaction. 21 infusion reactions occurred (30.4% of patients), 95% reported on the first day of the first cycle, being 90.4% of grade 1‐2. Only 1 suspension of treatment for infusion reaction grade 4 was reported, and 1 death occurred due to acute pulmonary edema on the second day in patient with severe heart failure prior to treatment. 55% of patients suffered some type of grade III‐IV toxicity: 40.5% neutropenia and 11.6% thrombocytopenia, 3 (4.3%) cases of grade III‐IV infection and 2 cases of liver toxicity (3%). Response at end of treatment (EOT) was assessed on 51 patients: overall responses (OR) rate was 90.2%. Complete remission (CR) 62.7% and partial remission (PR) 27.5%. 1 patient (2%) stable disease (SD) and 4 (7.8%) progressions occurred. Progression rate throughout the follow‐up was 21%. The median progression free survival (PFS) was not reached after a median follow‐up of 10 months. Estimated PFS at 12 months was 82% and 55.5% at 24 months. MRD in peripheral blood (PB) among 34 patients (49.3%) was evaluated at EOT: 64.7% negative and 35.3% positive. The median time to next treatment was not reached. 81% of patients continue without receiving second‐line treatment, and among the patients who progressed, 42% have still not initiated second line treatment. 7 deaths occurred (10%): 2 respiratory infections, 1 spontaneous bacterial peritonitis in a patient with HCV, 1 fulminating liver failure of unknown origin, 1 metastatic bladder cancer, 1 acute pulmonary edema, and 1 pulmonary thromboembolism. Median overall survival (OS) has not been reached. Estimated OS at 12 months is 90.2% and 83% at 24 months.
Summary/Conclusion:
Our data confirm the effectiveness of CI‐O regimen in fragile CLL patients in real‐life, with OR rates of 90%, and CR rates of 63%. 65% of patients achieved negative MRD at EOT in PB. Good safety profile and well‐tolerated regimen with low rate of serious infections and grade I‐II infusion‐related reactions which do not generally lead to treatment cessation.
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