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International Journal of Molecular... Jun 2024Busulfan, an indispensable medicine in cancer treatment, can cause serious reproductive system damage to males as a side effect of its otherwise excellent therapeutic...
Busulfan, an indispensable medicine in cancer treatment, can cause serious reproductive system damage to males as a side effect of its otherwise excellent therapeutic results. Its widespread use has also caused its accumulation in the environment and subsequent ecotoxicology effects. As a Chinese medicine, Wulingzhi (WLZ) has the effects of promoting blood circulation and improving female reproductive function. However, the potential effects of WLZ in male reproduction and in counteracting busulfan-induced testis damage, as well as its probable mechanisms, are still ambiguous. In this study, busulfan was introduced in a mouse model to evaluate its production of the testicular damage. The components of different WLZ extracts were compared using an untargeted metabolome to select extracts with greater efficacy, which were further confirmed in vivo. Here, we demonstrate abnormal spermatogenesis and low sperm quality in busulfan-injured testes. The WLZ extracts showed a strong potential to rehabilitate the male reproductive system; this effect was more prominent in room-temperature extracts. Additionally, both water and ethanol WLZ extracts at room temperature alleviated various busulfan-induced adverse effects. In particular, WLZ recovered spermatogenesis, re-activated arginine biosynthesis, and alleviated the increased oxidative stress and inflammation in the testis, ultimately reversing the busulfan-induced testicular injury. Collectively, these results suggest a promising approach to protecting the male reproductive system from busulfan-induced adverse side effects, as well as those of other similar anti-cancer drugs.
Topics: Male; Animals; Busulfan; Mice; Arginine; Testis; Spermatogenesis; Drugs, Chinese Herbal; Oxidative Stress; Reproduction; Spermatozoa
PubMed: 38928028
DOI: 10.3390/ijms25126320 -
Bioresource Technology Jun 2024Limited information is available on the removal of per- and polyfluoroalkyl substances (PFAS) in anaerobic digestion (AD). Τhe fate of six PFAS was studied in...
Limited information is available on the removal of per- and polyfluoroalkyl substances (PFAS) in anaerobic digestion (AD). Τhe fate of six PFAS was studied in thermophilic bioreactors in the presence of granular activated carbon (GAC) and voltage application. Reactors with GAC exhibited lower concentrations of volatile fatty acids and higher methane production compared to those with and without the application of voltage. Analysis of PFAS in dissolved and solid phase showed that their distribution was dependent on perfluorocarbon chain length and functional group. Mass balances showed that PFAS were not removed during conventional AD or after applying voltage; however, significant removal (up to 61 ± 8 %) was observed in bioreactors with GAC for perfluoroheptanoic acid (PFHpA), perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), and perfluorooctane sulfonate (PFOS). Biomass characterization showed that in these bioreactors, the relative abundance of Acinetobacter and Pseudomonas was higher, indicating their potential role in PFAS biotransformation.
PubMed: 38901748
DOI: 10.1016/j.biortech.2024.131013 -
Nature Communications Jun 2024Sulfur-containing scaffolds originating from small alkyl fragments play a crucial role in various pharmaceuticals, agrochemicals, and materials. Nonetheless, their...
Sulfur-containing scaffolds originating from small alkyl fragments play a crucial role in various pharmaceuticals, agrochemicals, and materials. Nonetheless, their synthesis using conventional methods presents significant challenges. In this study, we introduce a practical and efficient approach that harnesses hydrogen atom transfer photocatalysis to activate volatile alkanes, such as isobutane, butane, propane, ethane, and methane. Subsequently, these nucleophilic radicals react with SO to yield the corresponding sulfinates. These sulfinates then serve as versatile building blocks for the synthesis of diverse sulfur-containing organic compounds, including sulfones, sulfonamides, and sulfonate esters. Our use of flow technology offers a robust, safe and scalable platform for effectively activating these challenging gaseous alkanes, facilitating their transformation into valuable sulfinates.
PubMed: 38897988
DOI: 10.1038/s41467-024-49322-w -
Lipids in Health and Disease Jun 2024The management of male infertility continues to encounter an array of challenges and constraints, necessitating an in-depth exploration of novel therapeutic targets to...
BACKGROUND
The management of male infertility continues to encounter an array of challenges and constraints, necessitating an in-depth exploration of novel therapeutic targets to enhance its efficacy. As an eight-carbon medium-chain fatty acid, octanoic acid (OCA) shows promise for improving health, yet its impact on spermatogenesis remains inadequately researched.
METHODS
Mass spectrometry was performed to determine the fatty acid content and screen for a pivotal lipid component in the serum of patients with severe spermatogenesis disorders. The sperm quality was examined, and histopathological analysis and biotin tracer tests were performed to assess spermatogenesis function and the integrity of the blood-testis barrier (BTB) in vivo. Cell-based in vitro experiments were carried out to investigate the effects of OCA administration on Sertoli cell dysfunction. This research aimed to elucidate the mechanism by which OCA may influence the function of Sertoli cells.
RESULTS
A pronounced reduction in OCA content was observed in the serum of patients with severe spermatogenesis disorders, indicating that OCA deficiency is related to spermatogenic disorders. The protective effect of OCA on reproduction was tested in a mouse model of spermatogenic disorder induced by busulfan at a dose 30 mg/kg body weight (BW). The mice in the study were separated into distinct groups and administered varying amounts of OCA, specifically at doses of 32, 64, 128, and 256 mg/kg BW. After evaluating sperm parameters, the most effective dose was determined to be 32 mg/kg BW. In vivo experiments showed that treatment with OCA significantly improved sperm quality, testicular histopathology and BTB integrity, which were damaged by busulfan. Moreover, OCA intervention reduced busulfan-induced oxidative stress and autophagy in mouse testes. In vitro, OCA pretreatment (100 µM) significantly ameliorated Sertoli cell dysfunction by alleviating busulfan (800 µM)-induced oxidative stress and autophagy. Moreover, rapamycin (5 µM)-induced autophagy led to Sertoli cell barrier dysfunction, while OCA administration exerted a protective effect by alleviating autophagy.
CONCLUSIONS
This study demonstrated that OCA administration suppressed oxidative stress and autophagy to alleviate busulfan-induced BTB damage. These findings provide a deeper understanding of the toxicology of busulfan and a promising avenue for the development of novel OCA-based therapies for male infertility.
Topics: Male; Animals; Blood-Testis Barrier; Busulfan; Caprylates; Oxidative Stress; Mice; Sertoli Cells; Humans; Spermatogenesis; Autophagy; Infertility, Male; Testis; Spermatozoa; Adult
PubMed: 38862993
DOI: 10.1186/s12944-024-02157-2 -
Acta Crystallographica. Section E,... May 2024The synthesis, crystallization and characterization of a tri-fluoro-methane-sulfonate salt of 5,10,15,20-tetra-kis-(1-benzyl-pyridin-1-ium-4-yl)-21,23-por-phy-rin, CHN...
The synthesis, crystallization and characterization of a tri-fluoro-methane-sulfonate salt of 5,10,15,20-tetra-kis-(1-benzyl-pyridin-1-ium-4-yl)-21,23-por-phy-rin, CHN ·4CFSO ·4HO, ·OTf, are reported in this work. The reaction between 5,10,15,20-tetra-kis-(pyridin-4-yl)-21,23-porphyrin and benzyl bromide in the presence of 0.1 equiv. of Ca(OH) in CHCN under reflux with an N atmosphere and subsequent treatment with silver tri-fluoro-methane-sulfonate (AgOTf) salt produced a red-brown solution. This reaction mixture was filtered and the solvent was allowed to evaporate at room temperature for 3 d to give ·OTf. Crystal structure determination by single-crystal X-ray diffraction (SCXD) revealed that ·OTf crystallizes in the space group 2/. The asymmetric unit contains half a porphyrin mol-ecule, two tri-fluoro-methane-sulfonate anions and two water mol-ecules of crystallization. The macrocycle of tetra-pyrrole moieties is planar and unexpectedly it has coordinated Ca ions in occupational disorder. This Ca ion has only 10% occupancy (CHCaFNOS). The pyridinium rings bonded to methyl-ene groups from porphyrin are located in two different arrangements in almost orthogonal positions between the plane formed by the porphyrin and the pyridinium rings. The crystal structure features cation⋯π inter-actions between the Ca atom and the π-system of the phenyl ring of neighboring mol-ecules. Both tri-fluoro-methane-sulfonate anions are found at the periphery of , forming hydrogen bonds with water mol-ecules.
PubMed: 38845702
DOI: 10.1107/S205698902400447X -
International Journal of Molecular... May 2024Glucose transporters GLUT1 belong to the major facilitator superfamily and are essential to human glucose uptake. The overexpression of GLUT1 in tumor cells designates...
Glucose transporters GLUT1 belong to the major facilitator superfamily and are essential to human glucose uptake. The overexpression of GLUT1 in tumor cells designates it as a pivotal target for glycoconjugate anticancer drugs. However, the interaction mechanism of glycoconjugate drugs with GLUT1 remains largely unknown. Here, we employed all-atom molecular dynamics simulations, coupled to steered and umbrella sampling techniques, to examine the thermodynamics governing the transport of glucose and two glycoconjugate drugs (i.e., 6-D-glucose-conjugated methane sulfonate and 6-D-glucose chlorambucil) by GLUT1. We characterized the specific interactions between GLUT1 and substrates at different transport stages, including substrate recognition, transport, and releasing, and identified the key residues involved in these procedures. Importantly, our results described, for the first time, the free energy profiles of GLUT1-transporting glycoconjugate drugs, and demonstrated that H160 and W388 served as important gates to regulate their transport via GLUT1. These findings provide novel atomic-scale insights for understanding the transport mechanism of GLUT1, facilitating the discovery and rational design of GLUT1-targeted anticancer drugs.
Topics: Molecular Dynamics Simulation; Glucose Transporter Type 1; Glycoconjugates; Humans; Glucose; Biological Transport; Thermodynamics
PubMed: 38791523
DOI: 10.3390/ijms25105486 -
Cancer Medicine May 2024Type of conditioning regimen impacts the outcome of patients who undergo allogeneic HSCT since graft versus host disease (GVHD), infections, regimen related toxicities...
INTRODUCTION
Type of conditioning regimen impacts the outcome of patients who undergo allogeneic HSCT since graft versus host disease (GVHD), infections, regimen related toxicities (RRT) are important causes of post-transplant mortality. Despite the RRT profile of busulfan, it is frequently used worldwide. Treosulfan has advantages in terms of dose of administration, lower incidence of sinusoidal obstruction syndrome and lower neurotoxicity. We retrospectively investigated outcomes of patients who underwent allogeneic HSCT with treosulfan or busulfan based conditioning regimens in our institution.
METHODS
Treosulfan was administered to 94 patients while 85 patients received busulfan. Our outcomes were RRT, chronic and acute GVHD, relapse related mortality (RRM), non-relapse mortality, and fungal infection. The clinical follow up data, regarding the primary and secondary endpoints of our study, of the patients who received treosulfan or busulfan based conditioning regimens were statistically analyzed.
RESULTS
The median follow-up was 14 months for the treosulfan group while it was 11 months for the busulfan group (p = 0.16). RRT was 11.7% and 7.1% for treosulfan and busulfan respectively. The incidence of extensive chronic GVHD was less frequent in the treosulfan group compared to the busulfan group (15.7% vs. 32.1%) (p < 0.001). The incidence of acute GVHD (Grade 3 or higher) was 32.2% in the treosulfan group while it was 31.6% in the busulfan group. The RRM was 17% in the treosulfan group while it was 34% in the busulfan group. The non-relapse mortality was 35.5% and 29.4% in the treosulfan group and in the busulfan group respectively (p = 0.962).
CONCLUSION
Treosulfan, with a lower RRM, lower chronic GVHD incidence and with a similar RRT profile appears to be a safe alternative to busulfan.
Topics: Humans; Busulfan; Transplantation Conditioning; Female; Male; Hematopoietic Stem Cell Transplantation; Adult; Middle Aged; Graft vs Host Disease; Retrospective Studies; Young Adult; Transplantation, Homologous; Adolescent; Treatment Outcome; Aged; Antineoplastic Agents, Alkylating
PubMed: 38752476
DOI: 10.1002/cam4.7292 -
International Journal of Molecular... Apr 2024Gonadotoxic agents could impair spermatogenesis and may lead to male infertility. The present study aimed to evaluate the effect of IL-1β on the development of...
Gonadotoxic agents could impair spermatogenesis and may lead to male infertility. The present study aimed to evaluate the effect of IL-1β on the development of spermatogenesis from cells isolated from seminiferous tubules (STs) of normal and busulfan-treated immature mice in vitro. Cells were cultured in a 3D in vitro culture system for 5 weeks. We examined the development of cells from the different stages of spermatogenesis by immunofluorescence staining or qPCR analyses. Factors of Sertoli and Leydig cells were examined by qPCR analysis. We showed that busulfan (BU) treatment significantly reduced the expression of testicular IL-1β in the treated mice compared to the control group (CT). Cultures of cells from normal and busulfan-treated immature mice induced the development of pre-meiotic (Vasa), meiotic (Boule), and post-meiotic (acrosin) cells. However, the percentage of developed Boule and acrosin cells was significantly lower in cultures of busulfan-treated mice compared to normal mice. Adding IL-1β to both cultures significantly increased the percentages of Vasa, Boule, and acrosin cells compared to their controls. However, the percentage of Boule and acrosin cells was significantly lower from cultures of busulfan-treated mice that were treated with IL-1β compared to cultures treated with IL-1β from normal mice. Furthermore, addition of IL-1β to cultures from normal mice significantly increased only the expression of androgen receptor and transferrin but no other factors of Sertoli cells compared to their CT. However, the addition of IL-1β to cultures from busulfan-treated mice significantly increased only the expression of androgen-binding protein and the FSH receptor compared to their CT. Adding IL-1β to cultures of normal mice did not affect the expression of 3βHSD compared to the CT, but it significantly reduced its expression in cultures from busulfan-treated mice compared to the CT. Our findings demonstrate the development of different stages of spermatogenesis in vitro from busulfan-treated mice and that IL-1β could potentiate this development in vitro.
Topics: Animals; Busulfan; Spermatogenesis; Male; Interleukin-1beta; Mice; Sertoli Cells; Testis; Leydig Cells; Seminiferous Tubules; Cells, Cultured
PubMed: 38732137
DOI: 10.3390/ijms25094926 -
Acta Crystallographica. Section E,... Apr 2024Two 2,4,6-tri-methyl-aniline-based trifuloro-methane-sulfonate (tri-fluoro-methane-sulfonate) salts were synthesized and characterized by single-crystal X-ray...
Synthesis and crystal structures of ,2,4,6-tetra-methyl-anilinium tri-fluoro-methane-sulfonate and -iso-propyl-idene-,2,4,6-tetra-methyl-anilinium tri-fluoro-methane-sulfonate.
Two 2,4,6-tri-methyl-aniline-based trifuloro-methane-sulfonate (tri-fluoro-methane-sulfonate) salts were synthesized and characterized by single-crystal X-ray diffraction. ,2,4,6-Tetra-methyl-anilinium tri-fluoro-methane-sulfonate, [CHNH ][CFOS] (), was synthesized methyl-ation of 2,4,6-tri-methyl-aniline. -Iso-propyl-idene-,2,4,6-tetra-methyl-anilinium tri-fluoro-meth-ane-sulfonate, [CHN][CFOS] (), was synthesized in a two-step reaction where the imine, -iso-propyl-idene-2,4,6-tri-methyl-aniline, was first prepared a dehydration reaction to form the Schiff base, followed by methyl-ation using methyl tri-fluoro-methane-sulfonate to form the iminium ion. In compound , both hydrogen bonding and π-π inter-actions form the main inter-molecular inter-actions. The primary inter-action is a strong N-H⋯O hydrogen bond with the oxygen atoms of the tri-fluoro-methane-sulfonate anions bonded to the hydrogen atoms of the ammonium nitro-gen atom to generate a one-dimensional chain. The [CHNH ] cations form dimers where the benzene rings form a π-π inter-action with a parallel-displaced geometry. The separation distance between the calculated centroids of the benzene rings is 3.9129 (8) Å, and the inter-planar spacing and ring slippage between the dimers are 3.5156 (5) and 1.718 Å, respectively. For , the [CHN] cations also form dimers as in , but with the benzene rings highly slipped. The distance between the calculated centroids of the benzene rings is 4.8937 (8) Å, and inter-planar spacing and ring slippage are 3.3646 (5) and 3.553 Å, respectively. The major inter-molecular inter-actions in are instead a series of weaker C-H⋯O hydrogen bonds [C⋯O distances of 3.1723 (17), 3.3789 (18), and 3.3789 (18) Å], an inter-action virtually absent in the structure of . Fluorine atoms are not involved in strong directional inter-actions in either structure.
PubMed: 38721416
DOI: 10.1107/S2056989024003438 -
RSC Advances Apr 2024Chemical investigations of the sea urchin has led to separation of twelve compounds including one new sulfonic acid derivative (7) tridec-1-en-7-yl hydrogen sulphate...
Chemical investigations of the sea urchin has led to separation of twelve compounds including one new sulfonic acid derivative (7) tridec-1-en-7-yl hydrogen sulphate (1), first isolated from natural source, pyridine-3-yl methane sulfonate (2), and first isolated from marine organisms, boldine (12), in addition to nine known compounds (3-11), which were isolated for the first time from the genus Clypeaster. Their structures were elucidated based on spectroscopic analyses (1D and 2D NMR), HR-ESI-MS as well as comparison with the previously reported data. The antiviral activity of the crude extract and sulphated compounds were evaluated using MTT colorimetric assay against Coxsackie B4 virus. The crude extract and compound 1 showed very potent antiviral activity with a percentage of inhibition equal to 89.7 ± 0.53% and 86.1 ± 0.92%, respectively. Results of the molecular docking analysis of the isolated compounds within Coxsackie Virus B4 (COX-B4) X-ray crystal structure and quantum chemical calculation for three sulphated compounds are in a consistent adaptation with the antiviral results. The pharmacokinetic properties (ADME) of isolated compounds were determined.
PubMed: 38690113
DOI: 10.1039/d4ra01966k