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1.
Cardiol Young ; : 1-8, 2024 Apr 12.
Article in English | MEDLINE | ID: mdl-38606598

ABSTRACT

OBJECTIVE: We report the midterm results of our strategy utilizing transatrial-transpulmonary repair for tetralogy of Fallot at a single institution in a low-middle income country. METHODS: Medical records were retrospectively reviewed for 532 consecutive patients who underwent definitive repair of tetralogy of Fallot at our institution from 2010 to 2020. RESULTS: The median age and weight of patients in the study patients were 11.6 months (interquartile range, 8.6-17.2 months) and 7.5 kg (interquartile range, 6.8-8.8 kg). The pulmonary valve annulus was preserved (no transannular patch) in 398 patients (75%) and a mini-transannular patch was utilized for 134 patients (25%). The overall survival was 98% at 1 year, and 97% at 10-years follow-up, respectively. Longer postoperative ventilation time was the only risk factor correlated to early death (p = 0.004; Odds Risk, 1.04; 95% confidence intervals, 1.01-1.07). Fourteen patients required pulmonary valve replacement (2.6%, 14/532), four required surgical resection to relieve right ventricular outflow tract obstruction (0.8%, 4/532), and freedom from reoperation of the right ventricular outflow tract was 87% at 10 years. The only risk factor for right ventricular outflow tract reoperation was a postoperative systolic pressure gradient through the right ventricular outflow tract of greater than 50 mmHg (p < 0.001; HR, 47; 95% confidence intervals, 9.1-244). In total, 94.6% (471/489) of the patients were asymptomatic at the latest follow-up without significant arrhythmia. CONCLUSION: At our institution in an low-middle income country, the transatrial-transpulmonary repair for tetralogy of Fallot has excellent midterm results with few reoperations required. Close long-term follow-up is essential for patients who undergo repair with a mini-transannular patch and may eventually require pulmonary valve replacement.

2.
Sex Transm Dis ; 51(4): 254-259, 2024 Apr 01.
Article in English | MEDLINE | ID: mdl-38301628

ABSTRACT

BACKGROUND: Prostate-specific antigen (PSA), a biomarker of vaginal semen exposure, is less susceptible to bias than self-reported condom use behaviors. We examined the agreement of self-reported recent condomless sex (RCS) within couples and how these reports related to PSA detection. METHODS: We analyzed data from a study conducted in Vietnam, 2017 to 2020, of 500 different-sex couples using condoms and no other contraceptive method to prevent pregnancy for 6 months. We assessed enrollment and 6-month data from vaginal swabs and questionnaires from both partners. We calculated Prevalence-Adjusted Bias-Adjusted Kappa (PABAK) to evaluate agreement of men's and women's reports. Among couples with detected PSA, we assessed partner concordance of RCS reporting. RESULTS: At enrollment (n = 499), 79.8% of couples reported no RCS, 16.4% reported RCS, and 3.8% had partner-discordant reports (PABAK, 0.93; 95% confidence interval, 0.91-0.97). At 6 months (n = 472), 91.7% reported no RCS, 5.7% reported RCS, and 2.5% had partner-discordant reports (PABAK, 0.98; 95% confidence interval, 0.96-1.0). Among couples with detected PSA at baseline (11%, n = 55), 36% reported no RCS, 55% reported RCS, and 6% had discordant reports; at 6 months (6.6%, n = 31), 58% reported no RCS, 35% reported RCS, and 3% had discordant reports. CONCLUSIONS: We observed high agreement regarding condomless sex within couples in a population using condoms as contraception in Vietnam; however, a high proportion of couples with detected PSA had both partners reporting no RCS, indicating that concordant reporting of no RCS does not indicate lack of semen exposure.


Subject(s)
Prostate-Specific Antigen , Unsafe Sex , Male , Pregnancy , Humans , Female , Contraception , Safe Sex , Condoms , Surveys and Questionnaires , Sexual Partners
3.
Environ Int ; 184: 108456, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38277998

ABSTRACT

BACKGROUND: Mycotoxins are toxic fungal secondary metabolites that contaminate a wide spectrum of essential foods worldwide, such as grain-based products, nuts and spices, causing adverse health effects pertaining to their carcinogenic, nephrotoxic and hepatotoxic nature, among others. AIM: The aim of this systematic review (SR) is to systematically search for, appraise and synthesize primary research evidence to identify what is known about dietary mycotoxin-related health effects and what remains unknown, as well as the uncertainty around findings and the recommendations for the future. SEARCH STRATEGY AND ELIGIBILITY CRITERIA: Search strategies, as well as eligibility criteria were structured according to a predefined PECO (population, exposure, comparison, and outcome) research question and developed in an iterative scoping process. Several bibliographic databases, including Embase, Cochrane Library, Pubmed, Web of Science Core Collection and Scopus, will be searched. Primary research on any measured or modelled dietary exposure to a single or multiple mycotoxins, and adverse human health outcomes (i.e. cancer, non-carcinogenic diseases, and reproductive & developmental adverse outcomes) will be included, and references will be imported into Covidence. In vitro, ex vivo, in silico, animal and review studies, as well as expert's opinions, secondary literature, conference abstracts, presentations, posters, book chapters, dissertations and studies involving non-dietary mycotoxin exposure, will be excluded. STUDY SELECTION: Two independent reviewers will screen titles and abstracts, and review full-texts. Any disagreements will be resolved by a third reviewer based on two-third majority. DATA EXTRACTION: Data from retained eligible studies will be extracted by the principal reviewer, and peer-checked by a second reviewer. STUDY QUALITY ASSESSMENT: Eligible studies will be evaluated for risk of bias (Overall High-Quality Assessment Tool, OHAT) and certainty of evidence (Grading of Recommendations Assessment, Development and Evaluation, GRADE). EVIDENCE SYNTHESIS: A detailed summary of the included studies will be provided within a tabular format and narratively discussed. Heat maps will be constructed to provide information on available knowledge (gaps), and a meta-analysis may be performed based on the variability in predefined PECO elements and depending on the heterogeneity of studies. CONCLUSION: This protocol describes the methodology for the conduct of a SR on mycotoxin-related human health risks, that could guide future research and inform regulatory decisions, as emphasized by the European Commission within the field of regulatory risk assessment for emerging chemicals.


Subject(s)
Mycotoxins , Neoplasms , Animals , Humans , Dietary Exposure/adverse effects , Systematic Reviews as Topic , Mycotoxins/adverse effects , Meta-Analysis as Topic
4.
In Vivo ; 37(5): 2155-2160, 2023.
Article in English | MEDLINE | ID: mdl-37652493

ABSTRACT

BACKGROUND/AIM: The aim of this study was to evaluate the safety and efficacy of AFree oral spray, in combination with Standard of Care, in treating mild to moderate COVID-19 patients. This was an open-label, single-blinded, and controlled randomized clinical trial. PATIENTS AND METHODS: The study involved 1,252 patients, who were randomly assigned to either the control or study group, with 626 patients in each group. Patients in the control group were treated with Standard of Care recommended by the Ministry of Health of Vietnam, while patients in the study group received AFree oral spray in addition to Standard of Care for a period of 10 days. The clinical progression and outcomes of both groups were compared. RESULTS: The results showed that the proportion of patients with clinical symptoms on the 5th, 7th and 10th days were significantly lower in the study group (45.05%, 3.19% and 0%, respectively) compared to the control group (86.10%, 67.73% and 22.84%, respectively). Additionally, the rate of Real-time PCR test positivity for COVID-19 was significantly lower in the study group compared to the control group on the 4th, 7th, and 10th days (82.75% vs. 98.72%, 9.27% vs. 92.97%, and 1.12% vs. 50.48%, respectively). Furthermore, no side effects or complications related to AFree oral spray were recorded in the study group. CONCLUSION: The use of AFree oral spray resulted in significant improvements in clinical symptoms, recovery time, and viral clearance in COVID-19 patients with mild to moderate symptoms. This therapy has been shown to be safe and can be used as an adjuvant treatment for COVID-19 as well as other respiratory viral infections.


Subject(s)
COVID-19 , Humans , Prospective Studies , Oral Sprays , SARS-CoV-2 , Public Health , Disease Progression , Treatment Outcome
5.
In Vivo ; 37(4): 1743-1750, 2023.
Article in English | MEDLINE | ID: mdl-37369463

ABSTRACT

BACKGROUND/AIM: A prospective randomized, open-label, single-blinded clinical trial was conducted to evaluate the efficacy of AFree on the symptoms and course of moderate and severe COVID-19 in the field hospital. PATIENTS AND METHODS: Two hundred hospitalized patients diagnosed with COVID-19 were enrolled. The patients were randomized into 100 patients in the interventional AFree group and 100 in the control group. The AFree group patients were treated with AFree oral spray in conjunction with the standard COVID-19 treatment protocol, while the control group of patients were treated with only standard care. RESULTS: Patients of the AFree group demonstrated a remarkedly faster improvement in all COVID-19-related symptoms, resulting in a shorter time for complete recovery than the control group. More importantly, they showed a shorter time for complete viral clearance. Adding AFree to the standard of care protocol also significantly improved the restoration of taste and smell and reduced lung infiltration. Additionally, the patients in the AFree group also exhibited fewer adverse effects related to treatment. CONCLUSION: AFree oral spray is a simple-to-use, safe, and effective adjunctive treatment for moderate and severe COVID-19 cases. AFree oral spray was demonstrated to potentially be effective for COVID-19 prevention.


Subject(s)
COVID-19 , Humans , Oral Sprays , SARS-CoV-2 , COVID-19 Drug Treatment , Prospective Studies , Mobile Health Units , Treatment Outcome
6.
Nat Prod Res ; : 1-9, 2023 May 02.
Article in English | MEDLINE | ID: mdl-37129020

ABSTRACT

In our antioxidant screening of some Vietnamese plant extracts, the CHCl3-soluble fraction from Calotropis gigantea (L.) W.T.Aiton flowers showed moderate DPPH free radical scavenging activity with an IC50 value of 55.8 µg/mL. Thus, a further phytochemical study was carried out to obtain five alkaloids, including a new ß-carboline-type alkaloid, caloside H (1). These known compounds were identified as 5-hydroxy-(2-methoxymethyl)pyridine (2), nicotinic acid (3), p-(acetylamino)phenol (4), and thymine (5). These structures were determined based on the NMR spectroscopic analysis. In antioxidant assay, caloside H at concentration of 100 µM showed DPPH radical scavenging capacity with a percentage of inhibition of 40.2%. In addition, a plausible biosynthetic pathway for the formation of caloside H was proposed based on the Schiff base formation and Mannich-like reaction.

7.
Clin Transl Med ; 13(5): e1267, 2023 05.
Article in English | MEDLINE | ID: mdl-37226898

ABSTRACT

BACKGROUND: Renal medullary carcinoma (RMC) is a highly aggressive cancer in need of new therapeutic strategies. The neddylation pathway can protect cells from DNA damage induced by the platinum-based chemotherapy used in RMC. We investigated if neddylation inhibition with pevonedistat will synergistically enhance antitumour effects of platinum-based chemotherapy in RMC. METHODS: We evaluated the IC50 concentrations of the neddylation-activating enzyme inhibitor pevonedistat in vitro in RMC cell lines. Bliss synergy scores were calculated using growth inhibition assays following treatment with varying concentrations of pevonedistat and carboplatin. Protein expression was assessed by western blot and immunofluorescence assays. The efficacy of pevonedistat alone or in combination with platinum-based chemotherapy was evaluated in vivo in platinum-naïve and platinum-experienced patient-derived xenograft (PDX) models of RMC. RESULTS: The RMC cell lines demonstrated IC50 concentrations of pevonedistat below the maximum tolerated dose in humans. When combined with carboplatin, pevonedistat demonstrated a significant in vitro synergistic effect. Treatment with carboplatin alone increased nuclear ERCC1 levels used to repair the interstrand crosslinks induced by platinum salts. Conversely, the addition of pevonedistat to carboplatin led to p53 upregulation resulting in FANCD2 suppression and reduced nuclear ERCC1 levels. The addition of pevonedistat to platinum-based chemotherapy significantly inhibited tumour growth in both platinum-naïve and platinum-experienced PDX models of RMC (p < .01). CONCLUSIONS: Our results suggest that pevonedistat synergises with carboplatin to inhibit RMC cell and tumour growth through inhibition of DNA damage repair. These findings support the development of a clinical trial combining pevonedistat with platinum-based chemotherapy for RMC.


Subject(s)
Carcinoma, Medullary , Carcinoma, Renal Cell , Kidney Neoplasms , Humans , Carboplatin/pharmacology , Carboplatin/therapeutic use , Carcinoma, Renal Cell/drug therapy , Kidney Neoplasms/drug therapy
8.
SSM Popul Health ; 21: 101321, 2023 Mar.
Article in English | MEDLINE | ID: mdl-36660175

ABSTRACT

We examine the extent to which residential relocation within and between tenure types is associated with changes in mental health. We focus on four types of housing transition - rent-to-own, own-to-rent, own-to-own, and rent-to-rent - using Australian and UK panel data sets from 2001 to 2017. In both countries, transitions into homeownership and moves away from the mortgaged edges toward the unburdened mainstream of outright ownership are positively associated with mental health. On the other hand, shifts by mortgagors towards more precarious positions on the edges of ownership precipitate dips in mental health when there is exposure to high levels of payment and investment risks. Clearly, residential moves can both alleviate and introduce different kinds of risks that affect affordability. Moreover, tenure transitions have impacts on mental health beyond the impacts of payment and investment risks. However, we observe some cross-national differences in findings. In Australia, loss of homeownership has a negative impact on mental health that outweighs the mental health impacts of attaining ownership. In the UK, these findings are reversed. Acute housing affordability problems following moves in Australia, but not in the UK, are a significant driver of mental health outcomes. These differences have institutional explanations.

9.
Org Lett ; 24(37): 6767-6771, 2022 Sep 23.
Article in English | MEDLINE | ID: mdl-36099564

ABSTRACT

(IPr)GaCl3/AgSbF6, AgSbF6, and GaCl3 catalyzed substitution of the hydroxyl of secondary and tertiary propargylic alcohols with organoboronic acids via C-C bond formation, and GaCl3 effectively synthesized all-carbon quaternary propargylic centers. These catalysts performed the substitution at carbons bearing alkyl substituents, which has been problematic for other systems. Highly hindered carbon stereocenters were thus produced, including quaternary centers bearing doubly ortho-substituted aryl rings, that are difficult to access with traditional methods.

10.
Clin Infect Dis ; 75(1): e536-e544, 2022 08 24.
Article in English | MEDLINE | ID: mdl-35412591

ABSTRACT

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic is dominated by variant viruses; the resulting impact on disease severity remains unclear. Using a retrospective cohort study, we assessed the hospitalization risk following infection with 7 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants. METHODS: Our study includes individuals with positive SARS-CoV-2 reverse transcription polymerase chain reaction (RT-PCR) in the Washington Disease Reporting System with available viral genome data, from 1 December 2020 to 14 January 2022. The analysis was restricted to cases with specimens collected through sentinel surveillance. Using a Cox proportional hazards model with mixed effects, we estimated hazard ratios (HR) for hospitalization risk following infection with a variant, adjusting for age, sex, calendar week, and vaccination. RESULTS: In total, 58 848 cases were sequenced through sentinel surveillance, of which 1705 (2.9%) were hospitalized due to COVID-19. Higher hospitalization risk was found for infections with Gamma (HR 3.20, 95% confidence interval [CI] 2.40-4.26), Beta (HR 2.85, 95% CI 1.56-5.23), Delta (HR 2.28 95% CI 1.56-3.34), or Alpha (HR 1.64, 95% CI 1.29-2.07) compared to infections with ancestral lineages; Omicron (HR 0.92, 95% CI .56-1.52) showed no significant difference in risk. Following Alpha, Gamma, or Delta infection, unvaccinated patients show higher hospitalization risk, while vaccinated patients show no significant difference in risk, both compared to unvaccinated, ancestral lineage cases. Hospitalization risk following Omicron infection is lower with vaccination. CONCLUSIONS: Infection with Alpha, Gamma, or Delta results in a higher hospitalization risk, with vaccination attenuating that risk. Our findings support hospital preparedness, vaccination, and genomic surveillance.


Subject(s)
COVID-19 , SARS-CoV-2 , COVID-19/epidemiology , Hospitalization , Humans , Retrospective Studies , SARS-CoV-2/genetics , Washington/epidemiology
11.
PLoS One ; 17(2): e0263503, 2022.
Article in English | MEDLINE | ID: mdl-35176037

ABSTRACT

A key barrier to the consistent use of condoms is their negative effect on sexual pleasure. Although sexual pleasure is a primary motivation for engaging in sex and is an integral part of overall sexual health, most programs to improve sexual health operate within a pregnancy and disease-prevention paradigm. A new condom, CSD500 (Futura Medical Developments; Surrey, UK), containing an erectogenic drug was developed for use among healthy couples to improve sexual pleasure by increasing penile firmness, size and erection duration. We conducted a randomized controlled trial to test whether promoting the novel condom CSD500 for improved sexual pleasure is effective in reducing condomless sex compared to the provision of standard condoms with counseling for pregnancy and disease prevention. We randomized 500 adult, heterosexual, monogamous couples in Thanh Hoa province, Vietnam to receive either CSD500 (n = 248) or standard condoms (n = 252). At enrollment and after 2, 4, and 6 months, we interviewed women and sampled vaginal fluid to test for the presence of prostate-specific antigen (PSA), an objective, biological marker of recent semen exposure. We registered the protocol before trial initiation at ClinicalTrials.gov (identifier: NCT02934620). Overall, 11.0% of women were PSA positive at enrollment. The proportion of follow-up visits with PSA-positivity did not differ between the intervention (6.8%) and control arms (6.7%; relative risk, 1.01; 95% confidence interval, 0.66-1.54). Thus, we found no evidence that promoting an erectogenic condom to women in a monogamous, heterosexual relationship in Vietnam reduced their exposure to their partner's semen. These findings might not hold for other populations, especially those with a higher frequency of condomless sex.


Subject(s)
Condoms/statistics & numerical data , Penile Erection/physiology , Semen/chemistry , Sexual Behavior , Unsafe Sex/prevention & control , Adolescent , Adult , Case-Control Studies , Counseling , Female , Humans , Male , Prostate-Specific Antigen/analysis , Young Adult
12.
Nat Prod Res ; 36(15): 4026-4030, 2022 Aug.
Article in English | MEDLINE | ID: mdl-33729063

ABSTRACT

Bioactivity-guided isolation of the CHCl3-soluble fraction of the stems of Salacia chinensis L. (Celastraceae) was carried out to obtain a new 7',9-epoxylignan (1) and three 7,9':7',9-diepoxylignans (2-4). The absolute configuration of 1 was elucidated based on NMR and ECD spectroscopic data interpretation. All isolated lignans showed intermediate α-glucosidase inhibitory activity with the IC50 values ranging from 28.5 to 85.6 µM.


Subject(s)
Celastraceae , Lignans , Salacia , Lignans/pharmacology , Magnetic Resonance Spectroscopy , Plant Extracts/chemistry , Salacia/chemistry
13.
medRxiv ; 2022 Feb 16.
Article in English | MEDLINE | ID: mdl-34729567

ABSTRACT

BACKGROUND: The COVID-19 pandemic is dominated by variant viruses; the resulting impact on disease severity remains unclear. Using a retrospective cohort study, we assessed the hospitalization risk following infection with seven SARS-CoV-2 variants. METHODS: Our study includes individuals with positive SARS-CoV-2 RT-PCR in the Washington Disease Reporting System with available viral genome data, from December 1, 2020 to January 14, 2022. The analysis was restricted to cases with specimens collected through sentinel surveillance. Using a Cox proportional hazards model with mixed effects, we estimated hazard ratios (HR) for hospitalization risk following infection with a variant, adjusting for age, sex, calendar week, and vaccination. FINDINGS: 58,848 cases were sequenced through sentinel surveillance, of which 1705 (2.9%) were hospitalized due to COVID-19. Higher hospitalization risk was found for infections with Gamma (HR 3.20, 95%CI 2.40-4.26), Beta (HR 2.85, 95%CI 1.56-5.23), Delta (HR 2.28 95%CI 1.56-3.34) or Alpha (HR 1.64, 95%CI 1.29-2.07) compared to infections with ancestral lineages; Omicron (HR 0.92, 95%CI 0.56-1.52) showed no significant difference in risk. Following Alpha, Gamma, or Delta infection, unvaccinated patients show higher hospitalization risk, while vaccinated patients show no significant difference in risk, both compared to unvaccinated, ancestral lineage cases. Hospitalization risk following Omicron infection is lower with vaccination. CONCLUSION: Infection with Alpha, Gamma, or Delta results in a higher hospitalization risk, with vaccination attenuating that risk. Our findings support hospital preparedness, vaccination, and genomic surveillance. SUMMARY: Hospitalization risk following infection with SARS-CoV-2 variant remains unclear. We find a higher hospitalization risk in cases infected with Alpha, Beta, Gamma, and Delta, but not Omicron, with vaccination lowering risk. Our findings support hospital preparedness, vaccination, and genomic surveillance.

14.
Preprint in English | medRxiv | ID: ppmedrxiv-21264272

ABSTRACT

BackgroundThe COVID-19 pandemic is dominated by variant viruses; the resulting impact on disease severity remains unclear. Using a retrospective cohort study, we assessed the hospitalization risk following infection with seven SARS-CoV-2 variants. MethodsOur study includes individuals with positive SARS-CoV-2 RT-PCR in the Washington Disease Reporting System with available viral genome data, from December 1, 2020 to January 14, 2022. The analysis was restricted to cases with specimens collected through sentinel surveillance. Using a Cox proportional hazards model with mixed effects, we estimated hazard ratios (HR) for hospitalization risk following infection with a variant, adjusting for age, sex, calendar week, and vaccination. Findings58,848 cases were sequenced through sentinel surveillance, of which 1705 (2.9%) were hospitalized due to COVID-19. Higher hospitalization risk was found for infections with Gamma (HR 3.20, 95%CI 2.40-4.26), Beta (HR 2.85, 95%CI 1.56-5.23), Delta (HR 2.28 95%CI 1.56-3.34) or Alpha (HR 1.64, 95%CI 1.29-2.07) compared to infections with ancestral lineages; Omicron (HR 0.92, 95%CI 0.56-1.52) showed no significant difference in risk. Following Alpha, Gamma, or Delta infection, unvaccinated patients show higher hospitalization risk, while vaccinated patients show no significant difference in risk, both compared to unvaccinated, ancestral lineage cases. Hospitalization risk following Omicron infection is lower with vaccination. ConclusionInfection with Alpha, Gamma, or Delta results in a higher hospitalization risk, with vaccination attenuating that risk. Our findings support hospital preparedness, vaccination, and genomic surveillance. SummaryHospitalization risk following infection with SARS-CoV-2 variant remains unclear. We find a higher hospitalization risk in cases infected with Alpha, Beta, Gamma, and Delta, but not Omicron, with vaccination lowering risk. Our findings support hospital preparedness, vaccination, and genomic surveillance.

15.
Proc Natl Acad Sci U S A ; 118(29)2021 07 20.
Article in English | MEDLINE | ID: mdl-34253608

ABSTRACT

We hypothesize that trace amounts of phosphides formed in the mantle are a plausible abiotic source of the Venusian phosphine observed by Greaves et al. [Nat. Astron., https://doi.org/10.1038/s41550-020-1174-4 (2020)]. In this hypothesis, small amounts of phosphides (P3- bound in metals such as iron), sourced from a deep mantle, are brought to the surface by volcanism. They are then ejected into the atmosphere in the form of volcanic dust by explosive volcanic eruptions, which were invoked by others to explain the episodic changes of sulfur dioxide seen in the atmosphere [Esposito, Science 223, 1072-1074 (1984)]. There they react with sulfuric acid in the aerosol layer to form phosphine (2 P3- + 3H2SO4 = 2PH3 + 3SO42-). We take issue with the conclusion of Bains et al. [arXiv:2009.06499 (2020)] that the volcanic rates for such a mechanism would have to be implausibly high. We consider a mantle with the redox state similar to the Earth, magma originating deep in the mantle-a likely scenario for the origin of plume volcanism on Venus-and episodically high but plausible rates of volcanism on a Venus bereft of plate tectonics. We conclude that volcanism could supply an adequate amount of phosphide to produce phosphine. Our conclusion is supported by remote sensing observations of the Venusian atmosphere and surface that have been interpreted as indicative of currently active volcanism.

16.
Article in English | MEDLINE | ID: mdl-34306141

ABSTRACT

Two new stilbene derivatives, named strebluses C and D, were isolated from the EtOAc-soluble fraction of the stems of Streblus ilicifolius (Moraceae). Its absolute configuration was elucidated based on NMR spectroscopic data interpretation and optical rotation calculation. Streblus C possesses strong tyrosinase inhibitory activity with an IC50 value of 0.01 µM. Docking studies of 1 and 2 with oxy-tyrosinase were carried out to analyze their interactions. The analysis of the docked poses confirmed that 1 showed better binding affinity for oxy-tyrosinase than that of 2.

17.
Andrology ; 9(5): 1603-1616, 2021 09.
Article in English | MEDLINE | ID: mdl-33960147

ABSTRACT

BACKGROUND: Cancer treatment of prepubertal patients impacts future fertility due to the abolition of spermatogonial stem cells (SSCs). In macaques, spermatogenesis could be regenerated by intratesticular transplantation of SSCs, but no studies have involved cytotoxic treatment before puberty and transplantation after puberty, which would be the most likely clinical scenario. OBJECTIVES: To evaluate donor-derived functional sperm production after SSC transplantation to adult monkeys that had received testicular irradiation during the prepubertal period. MATERIALS AND METHODS: We obtained prepubertal testis tissue by unilaterally castrating six prepubertal monkeys and 2 weeks later irradiated the remaining testes with 6.9 Gy. However, because spermatogenic recovery was observed, we irradiated them again 14 months later with 7 Gy. Three of the monkeys were treated with GnRH-antagonist (GnRH-ant) for 8 weeks. The cryopreserved testis cells from the castrated testes were then allogeneically transplanted into the intact testes of all monkeys. Tissues were harvested 10 months later for analyses. RESULTS: In three of the six monkeys, 61%, 38%, and 11% of the epididymal sperm DNA were of the donor genotype. The ability to recover donor-derived sperm production was not enhanced by the GnRH-ant pretreatment. However, the extent of filling seminiferous tubules during the transplantation procedure was correlated with the eventual production of donor spermatozoa. The donor epididymal spermatozoa from the recipient with 61% donor contribution were capable of fertilizing rhesus eggs and forming embryos. Although the transplantation was done into the rete testis, two GnRH-ant-treated monkeys, which did not produce donor-derived epididymal spermatozoa, displayed irregular tubular cords in the interstitium containing testicular spermatozoa derived from the transplanted donor cells. DISCUSSION AND CONCLUSION: The results further support that sperm production can be restored in non-human primates from tissues cryopreserved prior to prepubertal and post-pubertal gonadotoxic treatment by transplantation of these testicular cells after puberty into seminiferous tubules.


Subject(s)
Adult Germline Stem Cells/transplantation , Puberty/radiation effects , Radiation Injuries, Experimental/therapy , Spermatogenesis/radiation effects , Stem Cell Transplantation , Animals , Cryopreservation , Gonadotropin-Releasing Hormone/antagonists & inhibitors , Hormone Antagonists/administration & dosage , Macaca mulatta , Male , Radiation Injuries, Experimental/physiopathology , Seminiferous Tubules , Spermatozoa/radiation effects , Testis/physiopathology , Testis/radiation effects
18.
Phytochemistry ; 183: 112646, 2021 Mar.
Article in English | MEDLINE | ID: mdl-33421887

ABSTRACT

A methanolic extract of the rhizomes of Boesenbergia rotunda showed potent preferential cytotoxicity against PANC-1 human pancreatic cancer cells under nutrient deficiency conditions with a PC50 value of 6.6 µg/mL. Bioactivity-guided phytochemical investigation of the rhizomes of B. rotunda led to the isolation of nine undescribed dimeric metabolites, panduratins Q-Y. Their structures were elucidated based on NMR, MS, and ECD spectroscopic data interpretation. Panduratins Q-S and U-W exhibited potent cytotoxicity towards PANC-1 cell line with the PC50 values ranging from 0.8 to 6.3 µM. Panduratin W, which possessed a cyclohexenylchalcone-linked flavanone skeleton, showed the most cytotoxicity with a PC50 value of 0.8 µM under nutrient-deprived medium.


Subject(s)
Antineoplastic Agents, Phytogenic , Pancreatic Neoplasms , Zingiberaceae , Antineoplastic Agents, Phytogenic/pharmacology , Antineoplastic Agents, Phytogenic/therapeutic use , Cell Line, Tumor , Drug Screening Assays, Antitumor , Humans , Pancreatic Neoplasms/drug therapy , Rhizome
19.
Org Lett ; 23(3): 702-705, 2021 Feb 05.
Article in English | MEDLINE | ID: mdl-33443442

ABSTRACT

A straightforward method for the undirected trifluoromethylation of unactivated methylene units was developed. The reaction proceeds in aqueous acetonitrile with Grushin's reagent, bpyCu(CF3)3, under broad-spectrum white-light irradiation. The trifluoromethylation tolerates a wide range of functional groups including ketones, esters, nitriles, amides, alcohols, and carboxylic acids. The C-H cleavage step is performed via intermolecular H atom abstraction, and the selectivities across a range of methylene units are reported. Mechanistic studies offer a general reaction coordinate for the overall transformation.

20.
Article in English | MEDLINE | ID: mdl-33488760

ABSTRACT

From a CHCl3-soluble extract of the stems of Semecarpus caudata (Anacardiaceae), two new diarylalkanoids, semedienone (1) and semetrienone (2), were isolated. Their structures were elucidated based on NMR spectroscopic data interpretation. These compounds possess strong tyrosinase inhibitory activity with the IC50 values of 0.033 and 0.11 µM, respectively. Docking studies of 1 and 2 with oxy-tyrosinase were carried out to analyze their interactions. Accordingly, semedienone (1) showed good interactions with the peroxide group and amino acid residues. The biosynthesis of the isolated diarylalkanoids was proposed.

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