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1.
Eur J Med Chem ; 274: 116566, 2024 Jun 02.
Article in English | MEDLINE | ID: mdl-38838545

ABSTRACT

Parkinson's disease (PD) is a common neurodegenerative disorder characterized by the loss of dopaminergic neurons in the substantia nigra pars compacta. The development of novel scaffolds for human monoamine oxidase B (hMAO-B) inhibitors with reversible properties represents an important strategy to improve the efficacy and safety for PD treatment. In the current work, we have devised and assessed two innovative derivative series serving as hMAO-B inhibitors. These series have utilized benzimidazole as a scaffold and strategically incorporated a primary amide group, which is recognized as a pivotal pharmacophore in subsequent activity screening and reversible mode of action. Among these compounds, 16d has emerged as the most potent hMAO-B inhibitor with an IC50 value of 67.3 nM, comparable to safinamide (IC50 = 42.6 nM) in vitro. Besides, 16d demonstrated good selectivity towards hMAO-B isoenzyme with a selectivity index over 387. Importantly, in line with the design purpose, 16d inhibited hMAO-B in a competitive and reversible manner (Ki = 82.50 nM). Moreover, 16d exhibited a good safety profile in both cellular and acute toxicity assays in mice. It also displayed ideal pharmacokinetic properties and blood-brain barrier permeability in vivo, essential prerequisites for central nervous system medicines. In the MPTP-induced PD mouse model, 16d significantly alleviated the motor impairment, especially muscle relaxation and motor coordination. Therefore, 16d, serving as a lead compound, holds instructive significance for subsequent investigations regarding its application in the treatment of PD.

2.
Biomed Pharmacother ; 176: 116786, 2024 May 27.
Article in English | MEDLINE | ID: mdl-38805971

ABSTRACT

Multitargeting has become a promising strategy for the development of anti-Alzheimer's disease (AD) drugs, considering the complexity of molecular mechanisms in AD pathology. In most pre-clinical studies, the effectiveness of these multi-targeted anti-AD drugs has been demonstrated but comprehensive safety assessments are lacking. Here, the safety evaluation of a novel multi-targeted candidate in AD (XYY-CP1106), characterized by its dual-property of iron chelation and monoamine oxidase B inhibition, was conducted by multifaceted analysis. Acute toxicity in mice was conducted to investigate the safety of oral administration and the maximum tolerated dose of the agent. In vitro Ames analysis, CHL chromosomal aberration analysis, and bone marrow micronucleus analysis were executed to evaluate the genotoxicity. A teratogenesis investigation in pregnant mice were meticulously performed to evaluate the teratogenesis of XYY-CP1106. Furthermore, a 90-day long-term toxicity analysis in rats was investigated to evaluate the cumulative toxicity after long-term administration. Strikingly, no toxic phenomena were found in all investigations, demonstrating relatively high safety profile of the candidate compound. The securing of safety heightened the translational significance of XYY-CP1106 as a novel multi-targeted anti-AD candidate, supporting the rationality of multitargeting strategy in the designs of smart anti-AD drugs.

3.
Bioorg Med Chem ; 105: 117726, 2024 May 01.
Article in English | MEDLINE | ID: mdl-38626642

ABSTRACT

5-Aminolevulinic acid (ALA) and its derivatives, serving as the endogenous precursor of the photosensitizer (PS) protoporphyrin IX (PpIX), successfully applied in tumor imaging and photodynamic therapy (PDT). ALA and its derivatives have been used to treat actinic keratosis (AK), basal cell carcinoma (BCC), and improve the detection of superficial bladder cancer. However, the high hydrophilicity of ALA and the conversion of PpIX to heme have limited the accumulation of PpIX, hindering the efficiency and potential application of ALA-PDT. This study aims to evaluate the PDT activity of three rationally designed series of ALA-HPO prodrugs, which were based on enhancing the lipophilicity of the prodrugs and reducing the labile iron pool (LIP) through HPO iron chelators to promote PpIX accumulation. Twenty-four ALA-HPO conjugates, incorporating amide, amino acid, and ester linkages, were synthesized. Most of the conjugates, exhibited no dark-toxicity to cells, according to bioactivity evaluation. Ester conjugates 19a-g showed promoted phototoxicity when tested on tumor cell lines, and this increased phototoxicity was strongly correlated with elevated PpIX levels. Among them, conjugate 19c emerged as the most promising (HeLa, IC50 = 24.25 ± 1.43 µM; MCF-7, IC50 = 43.30 ± 1.76 µM; A375, IC50 = 28.03 ± 1.00 µM), displaying superior photodynamic anticancer activity to ALA (IC50 > 100 µM). At a concentration of 80 µM, the fluorescence intensity of PpIX induced by compound 19c in HeLa, MCF-7, and A375 cells was 18.9, 5.3, and 2.8 times higher, respectively, than that induced by ALA. In conclusion, cellular phototoxicity showed a strong correlation with intracellular PpIX fluorescence levels, indicating the potential application of ALA-HPO conjugates in ALA-PDT.


Subject(s)
Aminolevulinic Acid , Antineoplastic Agents , Drug Screening Assays, Antitumor , Photochemotherapy , Photosensitizing Agents , Humans , Aminolevulinic Acid/pharmacology , Aminolevulinic Acid/chemistry , Photosensitizing Agents/pharmacology , Photosensitizing Agents/chemistry , Photosensitizing Agents/chemical synthesis , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Antineoplastic Agents/chemical synthesis , Structure-Activity Relationship , Molecular Structure , Pyridones/pharmacology , Pyridones/chemistry , Pyridones/chemical synthesis , Cell Line, Tumor , Protoporphyrins/chemistry , Protoporphyrins/pharmacology , Cell Proliferation/drug effects , Dose-Response Relationship, Drug , Cell Survival/drug effects , Prodrugs/pharmacology , Prodrugs/chemistry , Prodrugs/chemical synthesis
4.
Exp Eye Res ; 243: 109910, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38663720

ABSTRACT

Fluorescent proteins (FPs) have been widely used to investigate cellular and molecular interactions and trace biological events in many applications. Some of the FPs have been demonstrated to cause undesirable cellular damage by light-induced ROS production in vivo or in vitro. However, it remains unknown if one of the most popular FPs, tdTomato, has similar effects in neuronal cells. In this study, we discovered that tdTomato expression led to unexpected retinal dysfunction and ultrastructural defects in the transgenic mouse retina. The retinal dysfunction mainly manifested in the reduced photopic electroretinogram (ERG) responses and decreased contrast sensitivity in visual acuity, caused by mitochondrial damages characterized with cellular redistribution, morphological modifications and molecular profiling alterations. Taken together, our findings for the first time demonstrated the retinal dysfunction and ultrastructural defects in the retinas of tdTomato-transgenic mice, calling for a more careful design and interpretation of experiments involved in FPs.


Subject(s)
Electroretinography , Mice, Transgenic , Retina , Animals , Mice , Retina/metabolism , Luminescent Proteins/genetics , Luminescent Proteins/metabolism , Mice, Inbred C57BL , Visual Acuity/physiology , Mitochondria/metabolism , Red Fluorescent Protein
5.
J Obstet Gynaecol Res ; 50(5): 890-898, 2024 May.
Article in English | MEDLINE | ID: mdl-38403851

ABSTRACT

AIM: To investigate the impact of letrozole cotreatment progestin-primed ovarian stimulation (PPOS) (Le PPOS) in controlled ovarian stimulation (COS) and the pregnancy outcomes in frozen-thawed embryo transfer cycles. METHODS: This retrospective cohort study included women who underwent in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI). A total of 2575 cycles were included (1675 in the Le PPOS group and 900 in the PPOS group). The primary outcome was the clinical pregnancy rates. The secondary outcome was the live birth rates. RESULTS: In this study, propensity score matching (PSM) was performed to create a perfect match of 379 patients in each group. After matching, the numbers of oocytes retrieved, mature oocytes, fertilization, and clinical pregnancy rates were more favorable in the Le PPOS group than in the PPOS group (all p < 0.05). The multivariable analysis showed that the clinical pregnancy rate was higher in the Le PPOS than in the PPOS group (odds ratio = 1.46, 95% confidence interval: 1.05-2.04, p = 0.024) after adjusting for potentially confounding factors (age, anti-Müllerian hormone levels, antral follicular count, the type of embryo transferred, number of transferred embryos, body mass index, and follicular stimulating hormone and estradiol levels on starting day). CONCLUSIONS: This retrospective study with a limited sample size suggests that the Le PPOS protocol might be an alternative to the PPOS protocol in women undergoing COS and could lead to better pregnancy outcomes. The results should be confirmed using a formal randomized controlled trial.


Subject(s)
Fertilization in Vitro , Letrozole , Ovulation Induction , Pregnancy Rate , Progestins , Humans , Female , Letrozole/administration & dosage , Letrozole/pharmacology , Ovulation Induction/methods , Pregnancy , Adult , Retrospective Studies , Fertilization in Vitro/methods , Progestins/administration & dosage , Progestins/pharmacology , Sperm Injections, Intracytoplasmic/methods , Embryo Transfer/methods , Aromatase Inhibitors/administration & dosage , Aromatase Inhibitors/pharmacology
7.
BMC Med Genomics ; 17(1): 23, 2024 Jan 18.
Article in English | MEDLINE | ID: mdl-38238844

ABSTRACT

BACKGROUND: Antenatal Bartter syndrome is a life-threatening disease caused by a mutation in the MAGED2 gene located on chromosome Xp11. It is characterized by severe polyhydramnios and extreme prematurity. While most reported mutations are located in the exon region, variations in the intron region are rarely reported. METHODS: In our study, we employed whole exome sequencing and Sanger sequencing to genotype members of this family. Additionally, a minigene assay was conducted to evaluate the impact of genetic variants on splicing. RESULTS: Our findings reveal a novel intronic variant (NM_177433.3:c.1271 + 4_1271 + 7delAGTA) in intron 10 of the MAGED2 gene. Further analysis using the minigene assay demonstrated that this variant activated an intronic cryptic splice site, resulting in a 96 bp insertion in mature mRNA. CONCLUSIONS: Our results indicate that the novel intronic variant (c.1271 + 4_1271 + 7delAGTA) in intron 10 of the MAGED2 gene is pathogenic. This expands the mutation spectrum of MAGED2 and highlights the significance of intronic sequence analysis.


Subject(s)
Bartter Syndrome , Humans , Female , Pregnancy , Bartter Syndrome/genetics , Introns , Mutation , RNA Splicing , China , Antigens, Neoplasm/genetics , Adaptor Proteins, Signal Transducing/genetics
8.
Am J Pathol ; 194(2): 307-320, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38245252

ABSTRACT

Sleep deprivation (SD) is a global public health burden, and has a detrimental role in the nervous system. Retina is an important part of the central nervous system; however, whether SD affects retinal structures and functions remains largely unknown. Herein, chronic SD mouse model indicated that loss of sleep for 4 months could result in reductions in the visual functions, but without obvious morphologic changes of the retina. Ultrastructural analysis by transmission electron microscope revealed the deterioration of mitochondria, which was accompanied with the decrease of multiple mitochondrial proteins in the retina. Mechanistically, oxidative stress was provoked by chronic SD, which could be ameliorated after rest, and thus restore retinal homeostasis. Moreover, the supplementation of two antioxidants, α-lipoic acid and N-acetyl-l-cysteine, could reduce retinal reactive oxygen species, repair damaged mitochondria, and, as a result, improve the retinal functions. Overall, this work demonstrated the essential roles of sleep in maintaining the integrity and health of the retina. More importantly, it points towards supplementation of antioxidants as an effective intervention strategy for people experiencing sleep shortages.


Subject(s)
Sleep Deprivation , Thioctic Acid , Humans , Mice , Animals , Sleep Deprivation/complications , Sleep Deprivation/metabolism , Oxidative Stress/physiology , Antioxidants/pharmacology , Retina/metabolism , Thioctic Acid/pharmacology , Thioctic Acid/metabolism
9.
Arch Gynecol Obstet ; 309(2): 469-474, 2024 02.
Article in English | MEDLINE | ID: mdl-36708427

ABSTRACT

PURPOSE: To study whether the history of induced abortion has an effect on the assisted reproduction outcomes in patients undergoing in vitro fertilization-embryo transfer (IVF-ET). METHODS: 3045 patients who underwent IVF-ET in the Department of Human Reproductive Center of Renmin Hospital from January 2017 to June 2021. They were divided into two groups according to whether there was a history of induced abortion in the past, and the outcomes were compared between the two groups. RESULTS: The clinical pregnancy rate in the group with induced abortion history was lower than that in the group without induced abortion history (63.1% vs 67.1%), but the difference was not statistically significant (P = 0.059). The spontaneous abortion rate in the group with induced abortion history was higher than that in the group without induced abortion history (14.9% vs 11.2%) (P = 0.044). The live birth rate in the group with induced abortion history was lower than that in the group without induced abortion history (52.8% vs 59.0%) (P = 0.006). Stepwise logistic regression analysis showed that endometrial thickness (OR = 0.928, 95% CI = 0.886 ~ 0.972, P = 0.002) and live birth rate (OR = 0.682, 95% CI = 0.495 ~ 0.939, P = 0.019) were negatively correlated with induced abortion history. The rate of spontaneous abortion (OR = 1.452, 95% CI = 1.042 ~ 2.024, P = 0.028) was positively correlated with the history of induced abortion. CONCLUSIONS: The previous history of induced abortion is related to the outcomes of IVF /ICSI-ET, the endometrial thickness on HCG trigger day decreased, the risk of spontaneous abortion increased and the live birth rate decreased in patients with induced abortion history when undergoing IVF/ICSI-ET.


Subject(s)
Abortion, Induced , Abortion, Spontaneous , Pregnancy , Female , Humans , Abortion, Spontaneous/epidemiology , Pregnancy Rate , Embryo Transfer , Birth Rate , Fertilization in Vitro , Retrospective Studies
10.
Front Endocrinol (Lausanne) ; 14: 1295787, 2023.
Article in English | MEDLINE | ID: mdl-38155955

ABSTRACT

Objective: To explore the cycle characteristics and pregnancy outcomes of progestin-primed ovarian stimulation (PPOS) using fixed versus degressive doses of medroxyprogesterone acetate (MPA) in conjunction with letrozole (LE) in infertile women by propensity score matching (PSM) analysis. Design: A retrospective cohort study. Setting: Tertiary-care academic medical center. Population: A total of 3173 infertile women undergoing their first in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) treatment within the period from January 2017 to December 2020. Methods: A total of 1068 and 783 patients who underwent a fixed dose of MPA combined with LE and a degressive dose of MPA combined with LE protocols, respectively, were enrolled in this study. The freeze-all approach and later frozen-thawed embryo transfer (FET) were performed in both groups. Propensity score matching (1:1) was performed. Main outcome measures: The primary outcomes were the dosage of MPA and the incidence of premature luteinizing hormone (LH) surges. The secondary outcomes were the number of oocytes retrieved, the cumulative live birth rate (CLBR) and the fetal malformation rate. Results: We created a perfect match of 478 patients in each group. The dosage of MPA, the LH serum level on the eighth day of stimulation, progesterone (P) level and LH level on the hCG trigger day were significantly higher in the LE + fixed MPA group than in the LE + degressive MPA group (52.1 ± 13.1 mg vs. 44.9 ± 12.5 mg; 5.0 ± 2.7 IU/L vs. 3.7 ± 1.7 IU/L; 0.9 ± 0.5 ng/ml vs. 0.8 ± 0.5 ng/ml; 3.3 ± 2.4 IU/L vs. 2.8 ± 1.9 IU/L; P < 0.01). The duration of Gn, the number of follicles with diameter more than 16 mm on trigger day, the estradiol (E2) level on the hCG trigger day were lower in the LE + fixed MPA group than in the LE + degressive MPA group (9.7 ± 1.7 days vs. 10.3 ± 1.5 days; 5.6 ± 3.0 vs. 6.3 ± 3.0; 1752.5 ± 1120.8 pg/ml vs. 1997.2 ± 1108.5 pg/ml; P < 0.001). No significant difference was found in the incidence of premature LH surge, the number of oocytes retrieved, the number of top-quality embryos, clinical pregnancy rate (CPR), CLBR or fetal malformation rate between the two groups. Conclusion: The combination of a degressive MPA dose with LE proved effective in reducing the total MPA dosage with comparable premature LH surge and pregnancy outcomes in women undergoing the PPOS protocol.


Subject(s)
Infertility, Female , Progestins , Pregnancy , Humans , Female , Male , Medroxyprogesterone Acetate , Letrozole , Infertility, Female/therapy , Retrospective Studies , Propensity Score , Semen , Ovulation Induction/methods , Luteinizing Hormone
11.
J Enzyme Inhib Med Chem ; 38(1): 2270781, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37955252

ABSTRACT

Alzheimer's disease (AD) is a progressive brain disease characterised by progressive memory loss and cognition impairment, ultimately leading to death. There are three FDA-approved acetylcholinesterase inhibitors (donepezil, rivastigmine, and galantamine, AChEIs) for the symptomatic treatment of AD. Monoamine oxidase B (MAO-B) has been considered to contribute to pathologies of AD. Therefore, we reviewed the dual inhibitors of acetylcholinesterase (AChE) and MAO-B developed in the last five years. In this review, these dual-target inhibitors were classified into six groups according to the basic parent structure, including chalcone, coumarin, chromone, benzo-fused five-membered ring, imine and hydrazine, and other scaffolds. Their design strategies, structure-activity relationships (SARs), and molecular docking studies with AChE and MAO-B were analysed and discussed, giving valuable insights for the subsequent development of AChE and MAO-B dual inhibitors. Challenges in the development of balanced and potent AChE and MAO-B dual inhibitors were noted, and corresponding solutions were provided.


Subject(s)
Alzheimer Disease , Monoamine Oxidase , Humans , Monoamine Oxidase/metabolism , Acetylcholinesterase/metabolism , Alzheimer Disease/drug therapy , Monoamine Oxidase Inhibitors/pharmacology , Monoamine Oxidase Inhibitors/chemistry , Molecular Docking Simulation , Cholinesterase Inhibitors/pharmacology , Cholinesterase Inhibitors/chemistry , Structure-Activity Relationship
12.
Bioorg Chem ; 141: 106817, 2023 12.
Article in English | MEDLINE | ID: mdl-37690318

ABSTRACT

A novel series of phthalimide-hydroxypyridinone derivatives were rationally designed and evaluated as potential anti-Alzheimer's disease (AD) agents. Bioactivity tests showed that all compounds displayed great iron ions-chelating activity (pFe3+ = 17.07-19.52), in addition to potent inhibition of human monoamine oxidase B (hMAO-B). Compound 11n emerged as the most effective anti-AD lead compound with a pFe3+ value of 18.51, along with selective hMAO-B inhibitory activity (IC50 = 0.79 ± 0.05 µM, SI > 25.3). The results of cytotoxicity assays demonstrated that 11n showed extremely weak toxicity in PC12 cell line at 50 µM. Additionally, compound 11n displayed a cytoprotective effect against H2O2-induced oxidative damage. Moreover, compound 11n exhibited ideal blood-brain barrier (BBB) permeability in the parallel artificial membrane permeation assay (PAMPA), and significantly improved scopolamine-induced cognitive and memory impairment in mice behavioral experiments. In conclusion, these favorable experimental results suggested compound 11n deserved further investigation as an anti-AD lead compound.


Subject(s)
Alzheimer Disease , Mice , Humans , Animals , Alzheimer Disease/drug therapy , Alzheimer Disease/metabolism , Monoamine Oxidase Inhibitors/pharmacology , Monoamine Oxidase Inhibitors/therapeutic use , Hydrogen Peroxide , Structure-Activity Relationship , Cholinesterase Inhibitors/pharmacology , Cholinesterase Inhibitors/therapeutic use , Drug Design , Monoamine Oxidase/metabolism , Phthalimides/pharmacology , Amyloid beta-Peptides , Acetylcholinesterase/metabolism
13.
Ann N Y Acad Sci ; 1527(1): 60-74, 2023 09.
Article in English | MEDLINE | ID: mdl-37531162

ABSTRACT

With the increased use of artificial light and the prolonged use of optoelectronic products, light damage (LD) to the human retina has been identified as a global vision-threatening problem. While there is evidence of a significant correlation between light-induced retinal damage and age-related vision impairment in age-related macular degeneration, it is unclear how light-induced retinal degeneration manifests itself and whether there are agents capable of preventing the development of LD in the retina. This study investigated a mechanism by which blue light leads to photoreceptor death. By observing blue light exposure in retinal organoids and photoreceptor cells, we concluded that there could be significant apoptosis of the photoreceptors. We demonstrate that regenerating islet-derived 1 alpha (REG1A) prevents photoreceptors from undergoing this LD-induced apoptosis by increasing expression of the anti-apoptotic gene Bcl2 and downregulating expression of the pro-apoptotic gene Bax, resulting in reduced mitochondrial damage and improved aerobic capacity in photoreceptor cells. For the first time, REG1A has been shown to restore mitochondrial function and cell apoptosis after LD-induced damage, suggesting its potential application in the prevention and treatment of retinal vision loss.


Subject(s)
Retina , Retinal Degeneration , Humans , Retina/metabolism , Retinal Degeneration/prevention & control , Retinal Degeneration/metabolism , Photoreceptor Cells, Vertebrate/metabolism , Apoptosis , Light , Lithostathine
14.
Int J Biol Macromol ; 251: 126158, 2023 Aug 06.
Article in English | MEDLINE | ID: mdl-37549764

ABSTRACT

Monoamine oxidase is a flavin enzyme that catalyzes the oxidation of monoamine neurotransmitters in the brain. Various toxic by-products, aldehydes and hydrogen peroxide produced during the catalytic process, can cause oxidative stress and neuronal cell death. Overexpression of MAO-B and insufficient dopamine concentration are recognized as pathological factors in neurodegenerative diseases (NDs) including Parkinson's disease (PD) and Alzheimer's disease (AD). Therefore, the inhibition of MAO-B is an attractive target for the treatment of NDs. Despite significant efforts, few selective and reversible MAO-B inhibitors have been clinically approved. Natural products have emerged as valuable sources of lead compounds in drug discovery. Compounds such as chromone, coumarin, chalcone, caffeine, and aurone, present in natural structures, are considered as privileged scaffolds in the synthesis of MAO-B inhibitors. In this review, we summarized the structure-activity relationship (SAR) of MAO-B inhibitors based on the naturally privileged scaffolds over the past 20 years. Additionally, we proposed a balanced discussion on the advantages and limitations of natural scaffold-based MAO-B inhibitors with providing a future perspective in drug development.

15.
Org Biomol Chem ; 21(33): 6715-6718, 2023 Aug 23.
Article in English | MEDLINE | ID: mdl-37462425

ABSTRACT

Using CF3SO2Na as the CF3 radical source, an eco-friendly approach for electrochemistry-mediated radical cascade cyclization of N-methacryloyl-2-phenylbenzoimidazoles was described. This reaction features mild reaction conditions, readily available substrates, and moderate to good yields through the construction of two C-C bonds in one step.

16.
Gynecol Endocrinol ; 39(1): 2217263, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37236243

ABSTRACT

OBJECTIVE: To compare the effects of progestin-primed ovarian stimulation (PPOS) protocol and GnRH-a long protocol in infertility patients with normal ovarian reserve function undergoing invitro fertilization and embryo transfer. METHODS: A retrospective cohort study was conducted to analyze the clinical data of 2013 cycles of patients with normal ovarian reserve function who underwent invitro fertilization/intracytoplasmic sperm injection-embryo transfer (IVF/ICSI-ET) in the Department of Human Reproductive Center, Renmin Hospital, Hubei University of Medicine from January 2018 and June 2020. The PPOS protocol group included 679 cycles and GnRH-along protocol group included 1334 cycles, the pregnancy outcomes were compared between the two groups. RESULTS: The duration of Gn used and total Gn used dosage in the PPOS protocol group were less than those in the GnRH-along protocol group (Duration of Gn used: 10.05 ± 1.48 vs 11.90 ± 1.85 d, p < 0.001; Total Gn used dosage: 1944.49 ± 533.61 vs 2661.34 ± 987.97 IU, p < 0.001); The LH levels were significantly higher on HCG trigger day in PPOS protocol compared to GnRH-a long protocol (2.8 ± 1 ± 1.07 vs 1.01 ± 0.62 IU/L, p < 0.001), the E2 levels on HCG trigger day in PPOS protocol group was lower than that in the GnRH-a long protocol group (2135.92 ± 1387.00 vs 2417.01 ± 1010.70 pg/mL, p < 0. 001). The number of oocytes retrieved in the PPOS protocol group was lower than that in the GnRH-along protocol group (8.03 ± 2.86 vs 9.47 ± 2.64, p < 0.001). No significant differences were found in pregnancy outcome including clinical pregnancy rate, early miscarriage rate and ectopic pregnancy rate between the two group (p > 0.05); In addition, no severe OHSS occurred in the PPOS protocol group during ovulation induction, while 11 patients of severe ovarian hyperstimulation syndrome (OHSS) occurred in GnRH-a long protocol group (p < 0.001). CONCLUSION: The clinical efficacy of PPOS protocol combining embryo cryopreservation is comparable to that of GnRH-a long protocol in patients with normal ovarian reserve function, and the PPOS protocol is able to reduce the incidence of severe OHSS significantly.


Subject(s)
Ovarian Hyperstimulation Syndrome , Ovarian Reserve , Female , Pregnancy , Humans , Male , Progestins/pharmacology , Progestins/therapeutic use , Gonadotropin-Releasing Hormone , Fertilization in Vitro/methods , Retrospective Studies , Semen , Ovulation Induction/methods , Ovarian Hyperstimulation Syndrome/epidemiology , Pregnancy Rate , Steroids
17.
Int J Gynaecol Obstet ; 162(3): 913-921, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37010882

ABSTRACT

OBJECTIVES: To explore the effect of abnormally elevated serum alanine aminotransferase (ALT) on pregnancy outcomes in patients with moderate and severe ovarian hyperstimulation syndrome (OHSS) at disease onset. METHODS: This was a single-center retrospective cohort study conducted between January 1, 2014 and October 31, 2021. A total of 3550 fresh in vitro fertilization/intracytoplasmic sperm injection embryo transfer cycles were included, using Golan's three-degree, five-level classification to diagnose patients with OHSS. According to the patient's ALT level after diagnosis of OHSS, 123 (3.46%) patients with moderate-to-severe OHSS were divided into two groups. A control group included 3427 (96.54%) non-OHSS patients, and 91 (2.56%) abnormal ALT patients were matched with the control group for propensity scores. RESULTS: There was no difference in baseline data between the abnormal ALT and matched control groups. The incidence of obstetric complications was significantly higher in the abnormal ALT group than in the matched control group (P < 0.05). After adjusting for confounding factors, the incidence of obstetric complications in the abnormal ALT group was still higher than that in the normal ALT group (P < 0.05). CONCLUSION: In patients with moderate and severe OHSS, higher ALT levels resulted in an increased risk of obstetric and neonatal complications.


Subject(s)
Alanine Transaminase , Ovarian Hyperstimulation Syndrome , Female , Humans , Infant, Newborn , Pregnancy , Alanine Transaminase/blood , Fertilization in Vitro/methods , Ovarian Hyperstimulation Syndrome/epidemiology , Ovulation Induction/adverse effects , Pregnancy Rate , Retrospective Studies
18.
Molecules ; 28(5)2023 Mar 04.
Article in English | MEDLINE | ID: mdl-36903623

ABSTRACT

XYY-CP1106, a candidate compound synthesized from a hybrid of hydroxypyridinone and coumarin, has been shown to be remarkably effective in treating Alzheimer's disease. A simple, rapid and accurate high-performance liquid chromatography coupled with the triple quadrupole mass spectrometer (LC-MS/MS) method was established in this study to elucidate the pharmacokinetics of XYY-CP1106 after oral and intravenous administration in rats. XYY-CP1106 was shown to be rapidly absorbed into the blood (Tmax, 0.57-0.93 h) and then eliminated slowly (T1/2, 8.26-10.06 h). Oral bioavailability of XYY-CP1106 was (10.70 ± 1.72)%. XYY-CP1106 could pass through the blood-brain barrier with a high content of (500.52 ± 260.12) ng/g at 2 h in brain tissue. The excretion results showed that XYY-CP1106 was mainly excreted through feces, with an average total excretion rate of (31.14 ± 0.05)% in 72 h. In conclusion, the absorption, distribution and excretion of XYY-CP1106 in rats provided a theoretical basis for subsequent preclinical studies.


Subject(s)
Alzheimer Disease , Body Fluids , Rats , Animals , Chromatography, Liquid , Tandem Mass Spectrometry/methods , Tissue Distribution , Chromatography, High Pressure Liquid/methods , Feces/chemistry , Administration, Oral
19.
RSC Adv ; 13(8): 4958-4962, 2023 Feb 06.
Article in English | MEDLINE | ID: mdl-36762091

ABSTRACT

An unprecedented metal-free regioselective halogenation of 2H-indazoles has been revealed, which not only realized the highly selective synthesis of mono-halogenated products, but also completed poly-halogenations by fine tuning the reaction conditions. Various mono-/poly-/hetero-halogenated indazoles were obtained in moderate to excellent yields. Notably, this approach features environmentally friendly solvents, mild reaction conditions, simple execution and short reaction time.

20.
Materials (Basel) ; 16(2)2023 Jan 05.
Article in English | MEDLINE | ID: mdl-36676247

ABSTRACT

Huaguangjiao I refers to the ancient Chinese wooden shipwreck of the South Song Dynasty (1127-1279 AD) discovered in the South China Sea in 1996. From 2008 to 2017, the archaeological waterlogged wood was desalted using deionized water combined with ultrasonic treatment, and desalted using EDTA-2Na, EDTAHO, and NaH2PO4·2H2O solutions. In this paper, the degree of degradation of the modified waterlogged archaeological wood and the moisture and content of the main components were determined. X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), nanoindentation (NI), and scanning electron microscopy (SEM) were employed to investigate the state of wood degradation after desalination and desulfurization. The results showed that the water content of the wood was as high as 532~1149%, while the basic density was only 0.14~0.18 g/cm3, indicating that the wood had been seriously degraded. The holocellulose content was only 36-40%. Based on the XRD patterns, the degree of cellulose crystallinity in the modified wood was 14.08%. The elastic modulus and hardness of the ancient shipwreck wood after desalination and desulfurization were 1.28-4.31 and 0.10-0.28 GPa, respectively, according to nanoindentation. In addition, the FTIR spectra revealed that the biological deterioration of the modified wood caused cellulose and hemicellulose degradation, but no apparent lignin alteration occurred. The results could provide knowledge for appropriate dewatering, strengthening, and restoration strategies.

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