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Molecules (Basel, Switzerland) Jun 2024L. (Apiaceae) is a medicinal plant with a well-documented history in phytotherapy. The aim of the present work was to isolate isopimpinellin (5,8-methoxypsoralen; IsoP)...
L. (Apiaceae) is a medicinal plant with a well-documented history in phytotherapy. The aim of the present work was to isolate isopimpinellin (5,8-methoxypsoralen; IsoP) from the fruit of this plant and evaluate its biological activity against selected tumor cell lines. The methanol extract obtained with the use of an accelerated solvent extraction (ASE) method was the most suitable for the quantitative analysis of coumarins in the fruit matrix. The coumarin content was estimated by RP-HPLC/DAD, and the amount of IsoP was found to be 404.14 mg/100 g dry wt., constituting 24.56% of the total coumarin fraction (1.65 g/100 g). This, along with the presence of xanthotoxin (368.04 mg/100 g, 22.36%) and bergapten (253.05 mg/100 g, 15.38%), confirmed fruits as an excellent source of these compounds. IsoP was isolated (99.8% purity) by combined liquid chromatography/centrifugal partition chromatography (LC/CPC) and tested for the first time on its antiproliferative activity against human colorectal adenocarcinoma (HT29, SW620), osteosarcoma (Saos-2, HOS), and multiple myeloma (RPMI8226, U266) cell lines. MTT assay results (96 h incubation) demonstrated a dose- and cell line-dependent decrease in cell proliferation/viability, with the strongest effect of IsoP against the Saos-2 cell line (IC50; 42.59 µM), medium effect against U266, HT-29, and RPMI8226 (IC50 = 84.14, 95.53, and 105.0 µM, respectively), and very weak activity against invasive HOS (IC50; 321.6 µM) and SW620 (IC50; 711.30 µM) cells, as well as normal human skin fibroblasts (HSFs), with IC50; 410.7 µM. The mechanistic study on the Saos-2 cell line showed that IsoP was able to reduce DNA synthesis and trigger apoptosis via caspase-3 activation. In general, IsoP was found to have more potency towards cancerous cells (except for HOS and SW620) than against healthy cells. The Selective Index (SI) was determined, underlining the higher selectivity of IsoP towards cancer cells compared to healthy cells (SI = 9.62 against Saos-2). All these results suggest that IsoP might be a promising molecule in the chemo-prevention and treatment of primary osteosarcoma.
Topics: Humans; Fruit; Cell Line, Tumor; Furocoumarins; Plant Extracts; Ammi; Cell Proliferation; Antineoplastic Agents, Phytogenic; Apoptosis; Chromatography, High Pressure Liquid; Cell Survival
PubMed: 38930940
DOI: 10.3390/molecules29122874 -
Microorganisms Jun 2024Sulforaphane (SFN) is a natural isothiocyanate derived from cruciferous vegetables such as broccoli, Brussels sprouts, and cabbage. SFN plays a crucial role in...
Sulforaphane (SFN) is a natural isothiocyanate derived from cruciferous vegetables such as broccoli, Brussels sprouts, and cabbage. SFN plays a crucial role in maintaining redox homeostasis by interacting with the active cysteine residues of Keap1, leading to the dissociation and activation of NRF2 in various diseases. In this study, our objective was to investigate the impact of SFN on oxidative stress and pyroptosis in ()-infected macrophages. Our findings demonstrated that infection significantly increased the production of iNOS and ROS, indicating the induction of oxidative stress in macrophages. However, treatment with SFN effectively suppressed the expression of iNOS and COX-2 and reduced MDA and ROS levels, while enhancing GSH content as well as upregulating NRF2, HO-1, and NQO-1 expression in -infected RAW264.7 macrophages and primary peritoneal macrophages from WT mice. These results suggest that SFN mitigates oxidative stress by activating the NRF2 signaling pathway in -infected macrophages. Furthermore, excessive ROS production activates the NLRP3 signaling pathway, thereby promoting pyroptosis onset. Further investigations revealed that SFN effectively suppressed the expression of NLRP3, Caspase-1, and GSDMD, IL-1β, and IL-18 levels, as well as the production of LDH, suggesting that it may exhibit anti-pyroptotic effects through activation of the NRF2 signaling pathway and reductions in ROS production during infection. Moreover, we observed that SFN also inhibited the expression of NLRP3, ASC, Caspase1, and IL-1β along with LDH production in -infected primary peritoneal macrophages from NFR2 mice. This indicates that SFN can directly suppress NLRP3 activation and possibly inhibit pyroptosis initiation in an NRF2-independent manner. In summary, our findings demonstrate that SFN exerts its inhibitory effects on oxidative stress by activating the NRF2 signaling pathway in -infected macrophages, while it may simultaneously exert anti-pyroptotic properties through both NRF2-dependent and independent mechanisms targeting the NLRP3 signaling pathway.
PubMed: 38930573
DOI: 10.3390/microorganisms12061191 -
Microorganisms Jun 2024Accurate diagnostic techniques and effective therapeutic methods are required to treat . The application of chicken single-chain variable fragment (scFv) antibodies may...
Accurate diagnostic techniques and effective therapeutic methods are required to treat . The application of chicken single-chain variable fragment (scFv) antibodies may diagnose and treat . This study used the phage display technique to construct a chicken-derived immune scFv antibody library against . Total RNA was extracted from the spleens of five immunized chickens and reverse transcribed into cDNA. A fragment of scFv was produced by overlap extension PCR and cloned into a pHEN2 phagemid vector. After the package with the M13KO7 helper phage, the recombinant HpaA protein was used as a target antigen to validate the screening ability of our antibody library by bio-panning. The dilution counting results showed that the size of the primary antibody library was estimated to be 1 × 10 cfu/mL. PCR analysis of 47 clones from the library revealed that about 100% of the clones were positive with scFv fragments, and there were no identical sequences, indicating the good diversity of the antibody library. After three rounds of bio-panning, high-affinity antibodies against recombinant HpaA protein were successfully obtained. The selected antibody specifically recognized HpaA protein in nine different strains, confirming the screening ability of our library. The chicken immune scFv antibody library against was successfully constructed, and the antibody library's screening ability was validated by selecting specific scFv antibodies against recombinant HpaA and clinical strains. It provided a simple and rapid method to obtain antibodies against for diagnosis or treatment.
PubMed: 38930530
DOI: 10.3390/microorganisms12061148 -
Journal of Clinical Medicine Jun 2024: Dyslipidemia is a well-established risk factor for cardiovascular disease (CVD). However, among available drug treatments, only those targeted at lowering LDL-C and...
: Dyslipidemia is a well-established risk factor for cardiovascular disease (CVD). However, among available drug treatments, only those targeted at lowering LDL-C and consequently TC have demonstrated efficacy in preventing CVD. This is to say that the benefit for those with isolated high TG or low HDL-C is limited. The objective of this study is to examine the overlapping pattern of the four dyslipidemia components in US adult populations, which is important for quantifying the proportion of those who are less likely to benefit from lipid-lowering drugs and for a more precise use of the drug. : A total of 7822 participants aged over 20 with abnormalities in any of the four lipid parameters, excluding those on lipid-lowering medications, were included from the National Health and Nutrition Examination Survey (NHANES) cycles spanning 1999-2000 through 2017-2018. The proportions of different combinations of them were calculated and presented using area-proportional Euler plots. : High TC, high LDL-C, high TG, and low HDL-C were seen in 32.8% (95% CI: 31.3%-34.2%), 28.1% (95% CI: 26.6%-29.6%), 26.7% (95% CI: 25.4%-28.0%), and 65.9% (95% CI: 64.0%-67.7%) of the people with dyslipidemia, respectively. The proportions of dyslipidemia cases attributable to "high LDL-C or high TC" (irrespective of HDL-C and TG levels), "normal LDL-C, normal TC, but high TG" (irrespective of HDL-C level), and "normal LDL-C, normal TC, normal TG, but low HDL-C" (i.e., isolated low HDL-C) accounted for 37.5% (95% CI: 35.9%-39.1%), 18.3% (95% CI: 17.2%-19.4%), and 44.2% (95% CI: 42.5%-46.0%), respectively. : Some two-thirds of those with dyslipidemia had low HDL-C or high TG but normal LDL-C and normal TC. As these people are less likely to benefit from currently available drug treatments in terms of CVD prevention, it is important to identify other effective strategies or interventions targeted at them in order to achieve more precise and cost-effective management of dyslipidemia.
PubMed: 38930152
DOI: 10.3390/jcm13123624 -
Journal of Clinical Medicine Jun 2024This study is a Narrative Review that aims at investigating the implications of obesity, excessive gestational weight gain (GWG) and gestational diabetes mellitus... (Review)
Review
Gestational Metabolic Risk: A Narrative Review of Pregnancy-Related Complications and of the Effectiveness of Dietary, Exercise and Lifestyle Interventions during Pregnancy on Reducing Gestational Weight Gain and Preventing Gestational Diabetes Mellitus.
This study is a Narrative Review that aims at investigating the implications of obesity, excessive gestational weight gain (GWG) and gestational diabetes mellitus (GDM). Additionally, this Review seeks to explore the effectiveness of nutrition, and/or exercise interventions during pregnancy on reducing GWG and preventing GDM. The search in literature included studies that identified obesity, GWG, GDM and associated risks during pregnancy. Also, SR and MA focusing on interventions including diet, or physical activity (PA), or combined (i.e., lifestyle interventions) and their impact on metabolic risk during pregnancy, were identified through searches in PubMed, Cochrane Database of Systematic Reviews (CDSRs), and Scopus. The study findings suggest that lifestyle interventions during pregnancy may be effective in reducing excessive GWG. Regarding the prevention of GDM, results from studies evaluating lifestyle interventions vary. However, significant and less controversial results were reported from studies assessing the efficacy of exercise interventions, particularly in high-risk pregnant women. Lifestyle interventions during pregnancy may reduce excessive GWG. Exercise during pregnancy may prevent GDM, especially in high-risk pregnant women. Future research is warranted to tailor lifestyle interventions for optimal effectiveness during pregnancy.
PubMed: 38929991
DOI: 10.3390/jcm13123462 -
Journal of Personalized Medicine May 2024The term dystocia refers to labor characterized by a slow progression with delayed rates or even pauses in the dilation of the cervix or the descent of the fetus.... (Review)
Review
The term dystocia refers to labor characterized by a slow progression with delayed rates or even pauses in the dilation of the cervix or the descent of the fetus. Dystocia describes the deviation from the limits that define a normal birth and is often used as a synonym for the term pathological birth. Shoulder dystocia, also known as the manual exit of the shoulders during vaginal delivery on cephalic presentation, is defined as the "failure of the shoulders to spontaneously traverse the pelvis after delivery of the fetal head". This means that obstetric interventions are necessary to deliver the fetus's body after the head has been delivered, as gentle traction has failed. Abnormal labor (dystocia) is expressed and represented in partograms or by the prolongation of the latent phase or by slowing and pausing in the phases of cervical dilatation and fetal descent. While partograms are helpful in visualizing the progress of labor, regular use of them has not been shown to enhance obstetric outcomes considerably, and no partogram has been shown to be superior to others in comparative trials. Dystocia can, therefore, appear in any phase of the evolution of childbirth, so it is necessary to simultaneously assess all the factors that may contribute to its abnormal evolution, that is, the forces exerted, the weight, the shape, the presentation and position of the fetus, the integrity and morphology of the pelvis, and its relation to the fetus. When this complication occurs, it can result in an increased incidence of maternal morbidity, as well as an increased incidence of neonatal morbidity and mortality. Although several risk factors are associated with shoulder dystocia, it has proven impossible to recognize individual cases of shoulder dystocia in practice before they occur during labor. Various guidelines have been published for the management of shoulder dystocia, with the primary goal of educating the obstetrician and midwife on the importance of a preplanned sequence of maneuvers, thereby reducing maternal and neonatal morbidity and mortality.
PubMed: 38929807
DOI: 10.3390/jpm14060586 -
Medicina (Kaunas, Lithuania) Jun 2024Injuries represent a serious concern for football players, with a significant loss in terms of sport participation and long periods of rehabilitation. According to the... (Review)
Review
Injuries represent a serious concern for football players, with a significant loss in terms of sport participation and long periods of rehabilitation. According to the 2019/20 UEFA Élite Club Injury Report, the average incidence of injuries during training is 2.8 per 1000 h of training, with an average absence from training of 20 days. In addition, injured athletes are 4 to 7 times more likely to relapse than uninjured athletes. High workloads and reduced recovery periods represent two of the most important modifiable risk factors. In this context, prevention and an adequate rehabilitation protocol are vital in managing injuries, reducing their incidence, and improving the return to competition. In recent years, technological development has provided new tools in rehabilitation, and Virtual reality (VR) has shown interesting results in treating neurologic and orthopedic pathologies. Virtual Reality (VR) technology finds application in the sports industry as a tool to examine athletes' technical movements. The primary objective is to detect the biomechanical risk factors associated with anterior cruciate ligament injury. Additionally, VR can be used to train athletes in field-specific techniques and create safe and controlled therapeutic environments for post-injury recovery. Moreover, VR offers a customizable approach to treatment based on individual player data. It can be employed for both prevention and rehabilitation, tailoring the rehabilitation and training protocols according to the athletes' specific needs.
Topics: Humans; Virtual Reality; Athletic Injuries; Soccer; Risk Factors; Anterior Cruciate Ligament Injuries; Athletes
PubMed: 38929617
DOI: 10.3390/medicina60061000 -
Medicina (Kaunas, Lithuania) Jun 2024: Research on the impact of reduced time to emergent surgery in trauma patients has yielded inconsistent results. Therefore, this study investigated the relationship...
: Research on the impact of reduced time to emergent surgery in trauma patients has yielded inconsistent results. Therefore, this study investigated the relationship between waiting emergent surgery time (WEST) and outcomes in trauma patients. : This retrospective, multicenter study used data from the Tzu Chi Hospital trauma database. The primary clinical outcomes were in-hospital mortality, intensive care unit (ICU) admission, and prolonged hospital length of stay (LOS) of ≥30 days. : A total of 15,164 patients were analyzed. The median WEST was 444 min, with an interquartile range (IQR) of 248-848 min for all patients. Patients who died in the hospital had a shorter median WEST than did those who survived (240 vs. 446 min, < 0.001). Among the trauma patients with a WEST of <2 h, the median time was 79 min (IQR = 50-100 min). No significant difference in WEST was observed between the survival and mortality groups for patients with a WEST of <120 min (median WEST: 85 vs. 78 min, < 0.001). Multivariable logistic regression analysis revealed that WEST was not associated with an increased risk of in-hospital mortality (adjusted odds ratio [aOR] = 1.05, 95% confidence interval [CI] = 0.17-6.35 for 30 min ≤ WEST < 60 min; aOR = 1.12, 95% CI = 0.22-5.70 for 60 min ≤ WEST < 90 min; and aOR = 0.60, 95% CI = 0.13-2.74 for WEST ≥ 90 min). : Our findings do not support the "golden hour" concept because no association was identified between the time to definitive care and in-hospital mortality, ICU admission, and prolonged hospital stay of ≥30 days.
Topics: Humans; Female; Male; Retrospective Studies; Middle Aged; Hospital Mortality; Adult; Length of Stay; Wounds and Injuries; Aged; Intensive Care Units; Time Factors; Time-to-Treatment; Logistic Models
PubMed: 38929577
DOI: 10.3390/medicina60060960 -
Medicina (Kaunas, Lithuania) Jun 2024Oral contraceptives (OCs) are usually used to treat endometriosis; however, the evidence is inconsistent about whether OC use in the past, when given to asymptomatic...
Effect of Oral Contraceptive Use in Relation to Fertile Years on the Risk of Endometriosis in Women with Primary Infertility: A Ten-Year Single-Centre Retrospective Analysis.
Oral contraceptives (OCs) are usually used to treat endometriosis; however, the evidence is inconsistent about whether OC use in the past, when given to asymptomatic women, is protective against the development of future disease. We aimed to assess the relationship between the use of OCs and the likelihood of discovering endometriosis, considering the length of time under OCs during their fertile age. This was a monocentric retrospective cohort study in a tertiary-care University Hospital (Department of Human Reproduction, Division of Gynaecology and Obstetrics, University Medical Centre Ljubljana, Slovenia) carried out from January 2012 to December 2022. Reproductive-aged women scheduled for laparoscopic surgery for primary infertility and subsequent histopathological diagnosis of endometriosis were compared to women without an endometriosis diagnosis. They were classified based on the ratio of years of OC use to fertile years in four subgroups: never, <25%, between 25 and 50%, and >50. In total, 1923 women (390 with and 1533 without endometriosis) were included. Previous OC use was higher in those with endometriosis than controls (72.31% vs. 58.64%; = 0.001). Overall, previous OC usage was not related to histopathological diagnosis of endometriosis (aOR 1.06 [95% CI 0.87-1.29]). Women who used OCs for less than 25% of their fertile age had reduced risk of rASRM stage III endometriosis (aOR 0.50 [95% CI 0.26-0.95]; = 0.036) or superficial implants (aOR 0.88 [95% CI 0.58-0.95]; = 0.040). No significant results were retrieved for other rASRM stages. Using OCs for <25%, between 25 and 50%, or >50% of fertile age did not increase the risk of developing superficial endometriosis, endometriomas, or DIE. When OCs are used at least once, histological diagnoses of endometriosis are not increased. A protective effect of OCs when used for less than 25% of fertile age on superficial implants may be present. Prospective research is needed to corroborate the findings due to constraints related to the study's limitations.
Topics: Humans; Endometriosis; Female; Retrospective Studies; Adult; Contraceptives, Oral; Infertility, Female; Slovenia; Risk Factors; Cohort Studies; Time Factors
PubMed: 38929576
DOI: 10.3390/medicina60060959 -
Medicina (Kaunas, Lithuania) Jun 2024: New investigations have detected an enhanced probability for women to develop menstrual cycle alterations after anti-COVID-19 vaccination. Moreover, given that the...
: New investigations have detected an enhanced probability for women to develop menstrual cycle alterations after anti-COVID-19 vaccination. Moreover, given that the protective immunity provided by anti-COVID-19 vaccination appears to wane quickly, booster vaccination has been recommended. Nonetheless, whether adverse events arise from such repeated immunization has not been studied. : We studied the incidence of menstrual cycle alterations, the quantity of menstrual cycle alterations per subject, and of altered menstrual cycles in nonpregnant women of fertile age after anti-COVID-19 vaccination in a cohort of vaccinated female subjects by the means of a standardized questionary that was applied via telephone calls each month. Subjects that received up to four doses were studied for 6 months after each dose. We calculated the odds ratio for enhanced incidence, as well as quadratic functions for the tendencies. A sensitivity analysis excluding subjects taking hormonal birth control and those with polycystic ovary syndrome was performed. : Anti-COVID-19 vaccination enhanced the probability to develop menstrual cycle alterations (OR 1.52, CI at 95% 1.2-1.8, < 0.0001) and, interestingly, such a tendency was enhanced when subjects received more doses (R = 0.91). Furthermore, the same trends repeated for the quantity of alterations per subject, and of altered cycles. Such an effect was further demonstrated to be independent upon the vaccine brand being applied, the birth control status, and the diagnosis of polycystic ovary syndrome. : Vaccination is the most cost-effective measure for primary prevention and is considered to be safe. Nonetheless, in this article, we show data that suggest that repeated vaccination of adult female subjects may lead to an enhanced incidence of menstrual cycle-related adverse events, quantity of alterations per subject, and altered cycles. We therefore think that the development of new vaccine formulations that produce longer-lasting immunity is of paramount importance to reduce the potential for dose accumulation-dependent enhanced risk.
Topics: Humans; Female; Adult; COVID-19 Vaccines; Menstrual Cycle; COVID-19; SARS-CoV-2; Vaccination; Menstruation Disturbances; Cohort Studies; Immunization, Secondary; Incidence; Young Adult
PubMed: 38929574
DOI: 10.3390/medicina60060956