-
Archivio Italiano Di Urologia,... Jun 2024Single sperm cryopreservation (SSC) is a specific technique especially used in individuals with small numbers of sperm who suffered from non-obstructive azoospermia...
Pentoxifylline treatment as a safe method for selecting viable testicular spermatozoa before cryopreservation of a small numbers of spermatozoa in azoospermia individuals.
BACKGROUND
Single sperm cryopreservation (SSC) is a specific technique especially used in individuals with small numbers of sperm who suffered from non-obstructive azoospermia (NOA). Testicular specimens possess poor motility and low population of viable spermatozoa. Therefore, sperm selection methods such as applying pentoxifylline (PTX) may improve motility in these cases. The main aim of this study was to evaluate the protective effects of PTX on testicular spermatozoa before and after performing SSC.
METHODS
Thirty testicular samples were obtained from men with azoospermia. This study was conducted in two phases. Phase 1 evaluated the effect of PTX for sperm selection before SSC. Twenty testicular samples were divided to two experimental groups: SSC without (I) and with PTX treatment (II). For PTX treatment spermatozoa were incubated with PTX at 37°C for 30 min and only motile spermatozoa were selected for SSC. In phase 2, ten testicular samples were cryopreserved with SSC and warming procedure was carried out in droplet with and without PTX. Motility and viability rates, morphology by motile sperm organelle morphology examination (MSOME), DNA fragmentation by sperm chromatin dispersion test (SCD) and mitochondrial membrane potential (MMP) were evaluated.
RESULTS
In phase 1, post warm motility rate was higher in PTX exposed group compared to the unexposed group (25.6 ± 8.13 vs. 0.85 ± 2.1) (p > 0.00). Recovery rate, viability and morphology were not significantly different between groups. DNA integrity and MMP were also similar between both groups. In phase 2 although motility increased in PTX group compared to without PTX group (29.30 ± 12.73 vs. 1.90 ± 2.64) (p > 0.00), the viability rate was not different (70.40 ± 12.12 vs. 65.30 ± 11.87). All above mentioned parameters were similar between the two SSC groups.
CONCLUSIONS
Supplementation of testicular spermatozoa with PTX before cryopreservation increases motility and did not have adverse effects on viability, morphology, DNA integrity and MMP. PTX could be used as sperm selection method before single sperm cryopreservation, but PTX could not maintain motile the most of viable testicular sperms.
Topics: Male; Humans; Pentoxifylline; Cryopreservation; Azoospermia; Spermatozoa; Sperm Motility; Semen Preservation; DNA Fragmentation; Testis; Adult; Cell Survival; Membrane Potential, Mitochondrial
PubMed: 38934523
DOI: 10.4081/aiua.2024.12525 -
Pharmaceuticals (Basel, Switzerland) May 2024Selective COX-1 inhibitors are preferential therapeutic targets for platelet aggregation and clotting responses. In this study, we examined the selective...
Selective COX-1 inhibitors are preferential therapeutic targets for platelet aggregation and clotting responses. In this study, we examined the selective COX-1-inhibitory activities of four newly synthesized compounds, -, along with their abilities to inhibit platelet aggregation against ADP and collagen. The target compounds - were synthesized using the conventional method, sonication, and microwave-assisted methods. Microanalytical and spectral data were utilized to elucidate the structures of the new compounds -. Additionally, a spectral NMR experiment [NOESY] was conducted to emphasize the configuration around the double bond of the imine group C=N. The obtained results revealed no observed correlation between any of the neighboring protons, suggesting that the configuration at the C=N double bond is . Biological results revealed that all the screened compounds - might serve as selective COX-1 inhibitors. They showed IC values ranging from 0.71 μM to 4.82 μM against COX-1 and IC values ranging from 9.26 μM to 15.24 μM against COX-2. Their COX-1 selectivity indices ranged between 2.87 and 18.69. These compounds show promise as promising anti-platelet aggregation agents. They effectively prevented platelet aggregation induced by ADP with IC values ranging from 0.11 μM to 0.37 μM, surpassing the standard aspirin with an IC value of 0.49 μM. Additionally, they inhibited the platelet aggregation induced by collagen with IC values ranging from 0.12 μM to 1.03 μM, demonstrating superior efficacy compared to aspirin, which has an IC value of 0.51 μM. In silico molecular modeling was performed for all the target compounds within the active sites of COX-1 and COX-2 to rationalize their selective inhibitory activities towards COX-1. It was found that the binding interactions of the designed compounds within the COX-1 active site had remained unaffected by the presence of celecoxib. Molecular modeling and DFT calculations using the B3LYP/6-31+G (d,p) level were performed to study the stability of -forms with respect to -forms for the investigated compounds. A strong correlation was observed between the experimental observations and the quantum chemical descriptors.
PubMed: 38931377
DOI: 10.3390/ph17060710 -
Nutrients Jun 2024The use of natural products as alternatives to traditional pharmacological treatments in orthodontics is gaining interest due to their anti-inflammatory, antibacterial,... (Review)
Review
The use of natural products as alternatives to traditional pharmacological treatments in orthodontics is gaining interest due to their anti-inflammatory, antibacterial, and antioxidant properties. This systematic review synthesizes evidence from clinical trials to evaluate the efficacy of natural products in reducing inflammation and bacterial presence in orthodontic and orthognathic treatment settings. The database search was conducted across PubMed, Scopus, and Embase up to January 2024. The review focused on randomized controlled trials only. The selected studies centered on the anti-inflammatory, antibacterial, and antioxidant effects of natural products, adhering to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines for data extraction. Nine studies, totaling 358 participants, were included. Significant findings demonstrated a reduction in gingival inflammation by over 40% with the use of Aloe vera compared to chlorhexidine. Another study noted a decrease in bleeding on probing by 13.6 points in the treatment group over placebo. Additionally, honey showed a rapid modulation of plaque pH and significantly reduced bacterial counts of . Furthermore, the use of resveratrol emulgel was linked to substantial improvements in gingival health, with a reduction in the gingival index and probing pocket depth. The results indicate that natural products can significantly enhance orthodontic treatment outcomes by reducing inflammation and bacterial levels. These products offer effective alternatives to traditional treatments and show potential for integration into routine orthodontic care protocols. Further research is encouraged to standardize application methods and dosages to maximize clinical benefits and patient satisfaction.
Topics: Humans; Aloe; Anti-Bacterial Agents; Anti-Inflammatory Agents; Antioxidants; Biological Products; Chlorhexidine; Dentofacial Deformities; Gingivitis; Honey; Orthodontics; Plant Preparations; Randomized Controlled Trials as Topic; Resveratrol; Streptococcus mutans; Treatment Outcome
PubMed: 38931295
DOI: 10.3390/nu16121941 -
Nutrients Jun 2024Androgen production primarily occurs in Leydig cells located in the interstitial compartment of the testis. In aging males, testosterone is crucial for maintaining... (Review)
Review
Androgen production primarily occurs in Leydig cells located in the interstitial compartment of the testis. In aging males, testosterone is crucial for maintaining muscle mass and strength, bone density, sexual function, metabolic health, energy levels, cognitive function, as well as overall well-being. As men age, testosterone production by Leydig cells of the testes begins to decline at a rate of approximately 1% per year starting from their 30s. This review highlights recent findings concerning the use of natural polyphenolics compounds, such as flavonoids, resveratrol, and phenolic acids, to enhance testosterone production, thereby preventing age-related degenerative conditions associated with testosterone insufficiency. Interestingly, most of the natural polyphenolic antioxidants having beneficial effects on testosterone production tend to enhance the expression of the steroidogenic acute regulatory protein () gene in Leydig cells. The STAR protein facilitates the entry of the steroid precursor cholesterol inside mitochondria, a rate-limiting step for androgen biosynthesis. Natural polyphenolic compounds can also improve the activities of steroidogenic enzymes, hypothalamus-pituitary gland axis signaling, and testosterone bioavailability. Thus, many polyphenolic compounds such as luteolin, quercetin, resveratrol, ferulic acid phenethyl ester or gigantol may be promising in delaying the initiation of late-onset hypogonadism accompanying aging in males.
Topics: Male; Humans; Hypogonadism; Antioxidants; Polyphenols; Testosterone; Leydig Cells; Animals; Aging; Phosphoproteins; Resveratrol
PubMed: 38931170
DOI: 10.3390/nu16121815 -
Molecules (Basel, Switzerland) Jun 2024This review collects the synthetic modifications performed on andrographolide, a natural molecule derived from , for oncology applications. Various pharmacomodulations... (Review)
Review
This review collects the synthetic modifications performed on andrographolide, a natural molecule derived from , for oncology applications. Various pharmacomodulations were carried out, and the products were tested on different cancer cell lines. The impact of these modifications was analyzed with the aim of mapping the positions essential for activity to facilitate future research in this field. However, this study makes it clear that, in addition to structural modifications of the molecule, which can result in varying degrees of effectiveness in targeting interactions, the lipophilic capacity of the structures obtained through hemisynthesis is of significant importance.
Topics: Diterpenes; Humans; Antineoplastic Agents; Structure-Activity Relationship; Neoplasms; Andrographis; Cell Line, Tumor; Molecular Structure; Animals
PubMed: 38930949
DOI: 10.3390/molecules29122884 -
International Journal of Molecular... Jun 2024Our study aimed to investigate the role of ferroptosis in sevoflurane-induced hearing impairment and explore the mechanism of the microRNA-182-5p...
Our study aimed to investigate the role of ferroptosis in sevoflurane-induced hearing impairment and explore the mechanism of the microRNA-182-5p (miR-182-5p)/Glutathione Peroxidase 4 (GPX4) pathway in sevoflurane-induced ototoxicity. Immunofluorescence staining was performed using myosin 7a and CtBP2. Cell viability was assessed using the CCK-8 kit. Fe concentration was measured using FerroOrange and Mi-to-FerroGreen fluorescent probes. The lipid peroxide level was assessed using BODIPY 581/591 C11 and MitoSOX fluorescent probes. The auditory brainstem response (ABR) test was conducted to evaluate the hearing status. Bioinformatics tools and dual luciferase gene reporter analysis were used to confirm the direct targeting of miR-182-5p on GPX4 mRNA. GPX4 and miR-182-5p expression in cells was assessed by qRT-PCR and Western blot. Ferrostatin-1 (Fer-1) pretreatment significantly improved hearing impairment and damage to ribbon synapses in mice caused by sevoflurane exposure. Immunofluorescence staining revealed that Fer-1 pretreatment reduced intracellular and mitochondrial iron overload, as well as lipid peroxide accumulation. Our findings indicated that miR-182-5p was upregulated in sevoflurane-exposed HEI-OC1 cells, and miR-182-5p regulated GPX4 expression by binding to the 3'UTR of GPX4 mRNA. The inhibition of miR-182-5p attenuated sevoflurane-induced iron overload and lipid peroxide accumulation. Our study elucidated that the miR-182-5p/GPX4 pathway was implicated in sevoflurane-induced ototoxicity by promoting ferroptosis.
Topics: Ferroptosis; MicroRNAs; Sevoflurane; Phospholipid Hydroperoxide Glutathione Peroxidase; Animals; Mice; Ototoxicity; Signal Transduction; Cell Line; Male; Hearing Loss; Mice, Inbred C57BL; Phenylenediamines; Cyclohexylamines
PubMed: 38928480
DOI: 10.3390/ijms25126774 -
International Journal of Molecular... Jun 2024Endometritis is a common disease in animals, leading to disruption of reproductive processes and economic losses. Noradrenergic control of prostaglandin (PG)I2 formation...
Endometritis is a common disease in animals, leading to disruption of reproductive processes and economic losses. Noradrenergic control of prostaglandin (PG)I2 formation by inflamed endometrium is unknown. We determined the involvement of α1-, α2- and β-adrenoreceptors (ARs) in noradrenaline-influenced PGI synthase (PGIS) protein abundance and PGI2 release from porcine (1) endometrial explants with ()-induced inflammation in vivo, and (2) lipopolysaccharide (LPS)-treated endometrial epithelial cells. Experiment 1. suspension ( group) or saline (CON group) was injected into the uterine horns. In both groups, noradrenaline increased endometrial PGIS abundance and PGI2 release versus the control values, and it was higher in the group than in the CON group. In the CON group, a noradrenaline stimulating effect on both parameters takes place through α1D-, α2C- and β2-ARs. In the group, noradrenaline increased PGIS abundance and PGI2 release via α1A-, α2(B,C)- and β(1,2)-ARs, and PGI2 release also by α2A-ARs. Experiment 2. LPS and noradrenaline augmented the examined parameters in endometrial epithelial cells versus the control value. In LPS-treated cells, β(1,2)-ARs mediate in noradrenaline excitatory action on PGIS protein abundance and PGI2 release. β3-ARs also contribute to PGI2 release. Under inflammatory conditions, noradrenaline via ARs increases PGI2 synthesis and release from the porcine endometrium, including epithelial cells. Our findings suggest that noradrenaline may indirectly affect processes regulated by PGI2 in the inflamed uterus.
Topics: Animals; Female; Norepinephrine; Endometrium; Swine; Epoprostenol; Receptors, Adrenergic; Lipopolysaccharides; Inflammation; Escherichia coli; Endometritis; Epithelial Cells; Intramolecular Oxidoreductases; Cytochrome P-450 Enzyme System
PubMed: 38928020
DOI: 10.3390/ijms25126313 -
International Journal of Molecular... Jun 2024Platelets have a fundamental role in mediating hemostasis and thrombosis. However, more recently, a new idea is making headway, highlighting the importance of platelets... (Review)
Review
Platelets have a fundamental role in mediating hemostasis and thrombosis. However, more recently, a new idea is making headway, highlighting the importance of platelets as significant actors in modulating immune and inflammatory responses. In particular, platelets have an important role in the development of vascular amyloid-b-peptide(ab) deposits, known to play a relevant role in Alzheimer's disease (AD) through accumulation and deposition within the frontal cortex and hippocampus in the brain. The involvement of platelets in the pathogenesis of AD opens up the highly attractive possibility of applying antiplatelet therapy for the treatment and/or prevention of AD, but conclusive results are scarce. Even less is known about the potential role of platelets in mild cognitive impairment (MCI). The aim to this brief review is to summarize current knowledge on this topic and to introduce the new perspectives on the possible role of platelet activation as therapeutic target both in AD and MCI.
Topics: Humans; Blood Platelets; Alzheimer Disease; Platelet Activation; Neurodegenerative Diseases; Cognitive Dysfunction; Animals; Amyloid beta-Peptides; Platelet Aggregation Inhibitors
PubMed: 38927999
DOI: 10.3390/ijms25126292 -
Biomolecules Jun 2024Resveratrol, a phenylpropanoid compound, exhibits diverse pharmacological properties, making it a valuable candidate for health and disease management. However, the...
Resveratrol, a phenylpropanoid compound, exhibits diverse pharmacological properties, making it a valuable candidate for health and disease management. However, the demand for resveratrol exceeds the capacity of plant extraction methods, necessitating alternative production strategies. Microbial synthesis offers several advantages over plant-based approaches and presents a promising alternative. stands out among microbial hosts due to its safe nature, abundant acetyl-CoA and malonyl-CoA availability, and robust pentose phosphate pathway. This study aimed to engineer for resveratrol production. The resveratrol biosynthetic pathway was integrated into by adding genes encoding tyrosine ammonia lyase from , 4-coumarate CoA ligase from , and stilbene synthase from . This resulted in the production of 14.3 mg/L resveratrol. A combination of endogenous and exogenous malonyl-CoA biosynthetic modules was introduced to enhance malonyl-CoA availability. This included genes encoding acetyl-CoA carboxylase 2 from , malonyl-CoA synthase, and a malonate transporter protein from . These strategies increased resveratrol production to 51.8 mg/L. The further optimization of fermentation conditions and the utilization of sucrose as an effective carbon source in YP media enhanced the resveratrol concentration to 141 mg/L in flask fermentation. By combining these strategies, we achieved a titer of 400 mg/L resveratrol in a controlled fed-batch bioreactor. These findings demonstrate the efficacy of as a platform for the de novo production of resveratrol and highlight the importance of metabolic engineering, enhancing malonyl-CoA availability, and media optimization for improved resveratrol production.
Topics: Resveratrol; Yarrowia; Metabolic Engineering; Sucrose; Acyltransferases; Vitis; Coenzyme A Ligases; Malonyl Coenzyme A; Nicotiana; Rhodotorula; Fermentation; Arabidopsis; Ammonia-Lyases; Bacterial Proteins
PubMed: 38927115
DOI: 10.3390/biom14060712 -
Journal of Cardiothoracic Surgery Jun 2024We aimed to summarise the existing knowledge regarding antithrombotic medications following surgical aortic valve replacement (SAVR) using a biological valve prosthesis. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
We aimed to summarise the existing knowledge regarding antithrombotic medications following surgical aortic valve replacement (SAVR) using a biological valve prosthesis.
METHODS
We performed a meta-analysis of studies that reported the results of using antithrombotic medication to prevent thromboembolic events after SAVR using a biological aortic valve prosthesis and recorded the outcomes 12 months after surgery. Since no randomised controlled trials were identified, observational studies were included. The analyses were conducted separately for periods of 0-12 months and 3-12 months after surgery. A random effects model was used to calculate pooled outcome event rates and 95% confidence intervals (CIs).
RESULTS
The search yielded eight eligible observational studies covering 6727 patients overall. The lowest 0- to 12-month mortality was observed in patients with anticoagulation (2.0%, 95% CI 0.4-9.7%) and anticoagulation combined with antiplatelet therapy (2.2%, 95% CI 0.9-5.5%), and the highest was in patients without antithrombotic medication (7.3%, 95% CI 3.6-14.2%). Three months after surgery, mortality was lower in anticoagulant patients (0.5%, 95% CI 0.1-2.6%) than in antiplatelet patients (3.0%, 95% CI 1.2-7.4%) and those without antithrombotics (3.5%, 95% CI 1.3-9.3%). There was no eligible evidence of differences in stroke rates observed among medication strategies. At 0- to 12-month follow-up, all antithrombotic treatment regimens resulted in an increased bleeding rate (antiplatelet 4.2%, 95% CI 2.9-6.1%; anticoagulation 7.5%, 95% CI 3.8-14.4%; anticoagulation combined with antiplatelet therapy 8.3%, 95% CI 5.7-11.8%) compared to no antithrombotic medication (1.1%, 95% CI 0.4-3.4%). At 3- to 12-month follow-up, there was up to an eight-fold increase in the bleeding rate in patients with anticoagulation combined with antiplatelet therapy when compared to those with no antithrombotic medication. Overall, the evidence certainty was ranked as very low.
CONCLUSION
Although this meta-analysis reveals that anticoagulation therapy has a beneficial tendency in terms of mortality at 1 year after biological SAVR and suggests potential advantages in continuing anticoagulation beyond 3 months, it is limited by very low evidence certainty. The imperative for cautious interpretation and the urgent need for more robust randomised research underscore the complexity of determining optimal antithrombotic strategies in this patient population.
Topics: Humans; Fibrinolytic Agents; Heart Valve Prosthesis; Aortic Valve; Heart Valve Prosthesis Implantation; Thromboembolism; Bioprosthesis; Postoperative Complications; Anticoagulants; Platelet Aggregation Inhibitors
PubMed: 38926789
DOI: 10.1186/s13019-024-02863-z