Risk of disease flare in spondyloarthritis patients after tapering tumor necrosis factor inhibitors: A meta-analysis and literature review.

BACKGROUND: Tumor necrosis factor inhibitors (TNFis) have shown dramatic benefit in patients with spondyloarthritis (SpA). Tapering of TNFi medication may be considered in patients with sustained low disease activity because continued use of TNFis at standard doses may increase the risk of side effects including infections and impose an economic burden. However, the optimal TNFi tapering strategy for SpA patients with inactive disease has not been established. In the present study, we investigated whether tapering TNFi doses is associated with similar risk of disease flare to maintaining SpA patients on TNFis at the standard dosage. METHODS: The MEDLINE, Embase, and Cochrane databases were systemically searched to retrieve randomized control trials (RCTs) and observational studies published prior to August 2023, that compared disease flare in SpA (including axial SpA [axSpA], psoriatic arthritis [PsA], and SpA with IBD) patients who received standard TNFi doses and those who received a tapered dose of TNFi. Odds ratios (ORs) and 95% confidence intervals (CIs) were directly retrieved or calculated, and meta-analyses were performed. Bias was assessed using funnel plots with Begg and Mazumdar rank correlation / Egger's regression method. RESULTS: Among 2,237 SpA patients in the 12 studies (9 RCTs and 3 observational studies) retrieved, 1,301 received the standard TNFi dose, while 936 SpA patients underwent TNFi tapering. Of these, 216 (16.6%) standard-dose TNFi and 217 (23.2%) TNF-tapering patients experienced disease flares. The pooled OR for disease flare in TNFi-tapering patients was 1.601 (95% CI 1.276 - 2.008) compared with the standard-dose patients. The funnel plot showed no publication bias. CONCLUSIONS: The strategy of TNFi tapering was associated with a significantly increased risk of disease flare compared to maintaining SpA patients at the standard TNF dose. Further studies are needed to determine which patients can safely undergo tapering of TNFi and to develop safe tapering strategies.

The plant rhabdovirus viroporin P9 facilitates insect-mediated virus transmission in barley.

Potassium (K+) plays crucial roles in both plant development and immunity. However, the function of K+ in plant-virus interactions remains largely unknown. Here, we utilized Barley yellow striate mosaic virus (BYSMV), an insect-transmitted plant cytorhabdovirus, to investigate the interplay between viral infection and plant K+ homeostasis. The BYSMV accessory P9 protein exhibits viroporin activity by enhancing membrane permeability in Escherichia coli. Additionally, P9 increases K+ uptake in yeast (Saccharomyces cerevisiae) cells, which is disrupted by a point mutation of Glycine 14 to Threonine (P9G14T). Furthermore, BYSMV P9 forms oligomers and targets to both the viral envelope and the plant membrane. Based on the recombinant BYSMV-green fluorescent protein (BYGFP) virus, a P9-deleted mutant (BYGFPΔP9) was rescued and demonstrated infectivity within individual plant cells of Nicotiana benthamiana and insect vectors. However, BYGFPΔP9 failed to infect barley plants after transmission by insect vectors. Furthermore, infection of barley plants was severely impaired for BYGFP-P9G14T lacking P9 K+ channel activity. In vitro assays demonstrate that K+ facilitates virion disassembly and the release of genome RNA for viral mRNA transcription. Altogether, our results show that the K+ channel activity of viroporins is conserved in plant cytorhabdoviruses and plays crucial roles in insect-mediated virus transmission.

Bioactive peptides in dry-cured ham: A comprehensive review of preparation methods, metabolic stability, safety, health benefits, and regulatory frameworks.

Dry-cured hams contain abundant bioactive peptides with significant potential for the development of functional foods. However, the limited bioavailability of food-derived bioactive peptides has hindered their utilization in health food development. Moreover, there is insufficient regulatory information regarding bioactive peptides and related products globally. This review summarizes diverse bioactive peptides derived from dry-cured ham and by-products originating from various countries and regions. The bioactivity, preparation techniques, bioavailability, and metabolic stability of these bioactive peptides are described, as well as the legal and regulatory frameworks in various countries. The primary objectives of this review are to dig deeper into the functionality of dry-cured ham and provide theoretical support for the commercialization of bioactive peptides from food sources, especially the dry-cured ham.

Separation, enrichment and cytoprotection of antioxidant peptides from Xuanwei ham using aqueous two-phase extraction.

An ethanol/(NH4)2SO4 biphasic (aqueous two-phase) system was designed to effectively separate antioxidant peptides from Xuanwei ham, and its potential to prevent ultraviolet A-induced damage to skin cells was explored. Optimization via single factor experiments and response surface methodology revealed that under 20 % ethanol aqueous solution (w/w), 25.5 % (NH4)2SO4 aqueous solution (w/w), and pH 8.80 conditions, the optimal extraction ratio was 59.0 ± 1.73 %. In vitro antioxidant activity and cellular assays showed that the peptide purified in the upper phase exhibited strong antioxidant activity, increasing the viability of HaCat cells damaged by UVA irradiation from 56.14 ± 1.05 % to 66.3 ± 1.76 %. We used an in silico peptide screening strategy and identified 10 with potential antioxidant activity, emphasizing the important role of amino acids Pro, Gly, and Ala in antioxidant activity.

Comparing the Long-Term Cardiovascular Outcomes of Lumbo-Peritoneal, Ventriculo-Peritoneal, or Non-Shunting Treatment after Idiopathic Normal Pressure Hydrocephalus: A Nationwide Retrospective Cohort Study.

Purpose: With advances in medical technology, the average lifespan has increased, leading to a growing significance of idiopathic normal pressure hydrocephalus (iNPH), particularly in the elderly population. Most patients with iNPH have been treated either with ventriculo-peritoneal shunts (VPS) or conservative measures. However, lumbo-peritoneal shunts (LPS) have emerged as an alternative treatment option for iNPH in recent decades, extensive research still lacks comparing outcomes with LPS to those with VPS or non-surgical treatment. The aim of the resent study is to disclose the long-term therapeutic outcomes of LPS, VPS, and non-shunting in patients with iNPH. Methods: We used the National Health Insurance Research Database in Taiwan to assess the long-term outcomes of these treatment options. We enrolled 5,537 iNPH patients who received shunting surgery, of which 5,254 were VPS and 283 were LPS. To compare the difference between each group, matching was conducted by propensity score matching using a 1:1 ratio based on LPS patients. Primary outcomes included death and major adverse cardiovascular events (MACEs) Results: Our findings show that VPS resulted in significantly more MACEs than non-surgical treatment (Odds ratio: 1.83, 95% confidence interval: 1.16-2.90). In addition, both VPS and LPS groups had significantly lower overall mortality rates than non-shunting group. Moreover, LPS had lower overall mortality but similar MACEs rates to VPS. Conclusions: Based on these findings, we propose that the LPS is preferable to the VPS, and surgical treatment should be considered the primary choice over conservative treatment unless contraindications are present.

Waste to Wealth: Dynamics and metabolic profiles of the conversion of jackfruit flake into value-added products by different fermentation methods.

Thus far, little is known about whether jackfruit flake, a byproduct of jackfruit, can be used as a fermentation substrate to obtain value-added products through microbial fermentation. Here, jackfruit flake puree was fermented by three different ways: spontaneous fermentation (JF), inoculated with LAB (JFL), inoculated co-fermentation with LAB and yeast (JFC). In contrast to JF, the total polyphenol and flavonoid content and syndrome-associated enzyme inhibition are significantly increased in JFC at the end of fermentation. Electronic tongue analysis revealed that the JFC was significantly lower in astringency and higher in bitterness. 41 volatile compounds were identified during fermentation by HS-SPME-GC-MS, and JFC was richer in honey, rose, and fruity flavors. A total of 290 compounds were screened for discriminative pre- and post-fermentation differential metabolites by non-target metabolomics analysis. These results provide a potential reference for the conversion of jackfruit waste into functional products using fermentation.

A comparative study of laparoscopic choledocholithotomy with primary suture and T-tube drainage.

To investigate the clinical efficacy of laparoscopic choledocholithotomy with one-stage suture. The clinical data of 68 patients who underwent laparoscopic choledocholithotomy in our hospital from January 2015 to December 2021 were retrospectively analyzed. Among them, 29 patients underwent laparoscopic primary closure (PC group) and 39 underwent T-tube drainage (T-tube group). All patients were diagnosed with choledocholithiasis by B-ultrasound, CT or MRCP. The operation time, intraoperative blood loss, pain index, incidence of shoulder and back pain, postoperative satisfaction, postoperative bowel function recovery time, hospitalization time and expenses, and operation-related complications in the 2 groups were compared. 29 cases in PC group were successfully operated, and 39 cases in the T-tube drainage group (T-tube group) were successfully operated. The average operation time, postoperative bowel function recovery time, postoperative pain index, hospitalization time and expenses in PC group were significantly shorter or lower than those in T-tube group (P < .05) and the patient satisfaction in PC group was significantly higher than that in T-tube group (P < .05). In addition, the intraoperative blood loss and the incidence of surgical complications were similar between the 2 groups (P > .05). After laparoscopic common bile duct exploration, primary suture of common bile duct is a safe and effective treatment method, but the incidence of bile leakage is high, and clinical indications for surgery should be strictly controlled.

Macrophage P2Y6 receptor deletion attenuates atherosclerosis by limiting foam cell formation through phospholipase Cß/store-operated calcium entry/calreticulin/scavenger receptor A pathways.

BACKGROUND AND AIMS: Macrophage-derived foam cells play a causal role during the pathogenesis of atherosclerosis. P2Y6 receptor (P2Y6R) highly expressed has been considered as a disease-causing factor in atherogenesis, but the detailed mechanism remains unknown. This study aims to explore P2Y6R in regulation of macrophage foaming, atherogenesis, and its downstream pathways. Furthermore, the present study sought to find a potent P2Y6R antagonist and investigate the feasibility of P2Y6R-targeting therapy for atherosclerosis. METHODS: The P2Y6R expression was examined in human atherosclerotic plaques and mouse artery. Atherosclerosis animal models were established in whole-body P2Y6R or macrophage-specific P2Y6R knockout mice to evaluate the role of P2Y6R. RNA sequencing, DNA pull-down experiments, and proteomic approaches were performed to investigate the downstream mechanisms. High-throughput Glide docking pipeline from repurposing drug library was performed to find potent P2Y6R antagonists. RESULTS: The P2Y6R deficiency alleviated atherogenesis characterized by decreasing plaque formation and lipid deposition of the aorta. Mechanically, deletion of macrophage P2Y6R significantly inhibited uptake of oxidized low-density lipoprotein through decreasing scavenger receptor A expression mediated by phospholipase Cß/store-operated calcium entry pathways. More importantly, P2Y6R deficiency reduced the binding of scavenger receptor A to CALR, accompanied by dissociation of calreticulin and STIM1. Interestingly, thiamine pyrophosphate was found as a potent P2Y6R antagonist with excellent P2Y6R antagonistic activity and binding affinity, of which the pharmacodynamic effect and mechanism on atherosclerosis were verified. CONCLUSIONS: Macrophage P2Y6R regulates phospholipase Cß/store-operated calcium entry/calreticulin signalling pathway to increase scavenger receptor A protein level, thereby improving foam cell formation and atherosclerosis, indicating that the P2Y6R may be a potential therapeutic target for intervention of atherosclerotic diseases using P2Y6R antagonists including thiamine pyrophosphate.

Thalamic connectivity topography in newborns with spina bifida: association with neurological functional level but not developmental outcome at 2 years.

Spina bifida affects spinal cord and cerebral development, leading to motor and cognitive delay. We investigated whether there are associations between thalamocortical connectivity topography, neurological function, and developmental outcomes in open spina bifida. Diffusion tensor MRI was used to assess thalamocortical connectivity in 44 newborns with open spina bifida who underwent prenatal surgical repair. We quantified the volume of clusters formed based on the strongest probabilistic connectivity to the frontal, parietal, and temporal cortex. Developmental outcomes were assessed using the Bayley III Scales, while the functional level of the lesion was assessed by neurological examination at 2 years of age. Higher functional level was associated with smaller thalamo-parietal, while lower functional level was associated with smaller thalamo-temporal connectivity clusters (Bonferroni-corrected P < 0.05). Lower functional levels were associated with weaker thalamic temporal connectivity, particularly in the ventrolateral and ventral anterior nuclei. No associations were found between thalamocortical connectivity and developmental outcomes. Our findings suggest that altered thalamocortical circuitry development in open spina bifida may contribute to impaired lower extremity function, impacting motor function and independent ambulation. We hypothesize that the neurologic function might not merely be caused by the spinal cord lesion, but further impacted by the disruption of cerebral neuronal circuitry.

Impact of anti-tumor necrosis factor treatment on lipid profiles in Korean patients with ankylosing spondylitis.

Objective: To investigate the effects of anti-tumor necrosis factor (TNF) treatment on lipid profiles and identify risk factors for an increase in total cholesterol (TC) after the anti-TNF treatment in ankylosing spondylitis (AS) patients. Methods: This retrospective cohort study analyzed AS patients who received the first-line anti-TNF treatment. Patients with at least nine months of follow-up were included; those who were under 18 years or on any lipid-lowering agent were excluded. A linear mixed model was used to assess the impact of anti-TNF inhibitors on disease activity and lipid profile (TC, low-density lipoprotein [LDL], high-density lipoprotein [HDL], and triglycerides [TG]). Univariable and multivariable linear regression were used to identify risk factors for an increase in TC after 3 months of anti-TNF treatment. Results: A total of 315 AS patients were enrolled (78.1% male, median age 32.0 [26.0~41.0]). TC, HDL, and TG levels significantly increased particularly within the first 3 months of anti-TNF treatment, while LDL level did not show significant changes. Changes in inflammatory markers and lipid particles (TC, LDL, TG) were correlated over time, but HDL showed no significant correlation. Older age, higher baseline erythrocyte sedimentation rate, and lower baseline LDL level were related to an increase in TC after 3 months of the anti-TNF treatment. Conclusion: In AS patients, anti-TNF treatment has been found to increase lipid particles, potentially due to its anti-inflammatory effects. Future research should explore the underlying mechanism and the clinical implications of dyslipidemia, particularly the occurrence of cardiovascular events, following anti-TNF treatment in AS patients.

[Mechanism of albiflorin in improvement of Alzheimer's disease based on network pharmacology and in vitro experiments].

This study aimed to explore the mechanism of albiflorin in the treatment of Alzheimer's disease(AD) based on network pharmacology, molecular docking, and in vitro experiments. Network pharmacology was used to predict the potential targets and pathways of albiflorin against AD, and molecular docking technology was used to verify the binding affinity of albiflorin to key target proteins. Finally, the AD cell model was induced by Aß_(25-35) in rat pheochromocytoma(PC12) cells and intervened by albiflorin to validate core targets and pathways. The results of network pharmacological analysis showed that albiflorin acted on key targets such as mitogen-activated protein kinase-1(MAPK1 or ERK2), albumin(ALB), epidermal growth factor receptor(EGFR), caspase-3(CASP3), and sodium-dependent serotonin transporter(SLC6A4), and signaling pathways such as MAPK, cAMP, and cGMP-PKG. The results of molecular docking showed that albiflorin had strong binding affinity to MAPK1(ERK2). In vitro experiments showed that compared with the blank group, the model group showed decreased cell viability, decreased expression level of B-cell lymphoma 2(Bcl-2), increased Bcl-2-associated X protein(Bax), and reduced phosphorylation level of extracellular signal-regulated kinase 1/2(ERK1/2) and the relative expression ratio of p-ERK1/2 to ERK1/2. Compared with the model group, the albiflorin group showed potentiated cell viability, up-regulated expression of Bcl-2, down-regulated Bax, and increased phosphorylation level of ERK1/2 and the relative expression ratio of p-ERK1/2 to ERK1/2. These results suggest that the mechanism of albiflorin against AD may be related to its activation of the MAPK/ERK signaling pathway and its inhibition of neuronal apoptosis.

Seven new secondary metabolites isolated from roots of Lespedeza bicolor.

Chemical investigation of a methanol extract obtained from the roots of Lespedeza bicolor identified one new pterocarpene (1), three new pterocarpans (2-4), and three new arylbenzofurans (5-7), and two known compounds (8 and 9). Their structures were determined by interpretations obtained from combined UV, NMR, and HRTOFMS spectroscopic data. Furthermore, the absolute configurations of compounds 2 and 3 were established by the combination of electronic circular dichroism (ECD) calculations and NMR calculations with DP4+ probability analysis. All isolated compounds (1-9) were evaluated for cytotoxicity against the human lung carcinoma cell line A549 and the human hepatoma cell line Huh-7. Compound 4 showed antiproliferative activity against A549 cell line with IC50 value of 24.9 µM. Furthermore, compound 9 exhibited cytotoxicity against Huh-7 cell line with IC50 value of 68.7 µM.

Comparison of the clinical effects of lamina replantation and screw fixation after laminectomy in the treatment of intraspinal tumours.

INTRODUCTION: Intraspinal tumours are common diseases in neurosurgery and spinal surgery. Due to the fact that most of them are benign tumours, surgical resection is usually effective, and it is also the main treatment for these tumours. To maintain the stability of the spine and to reduce the incidence of kyphosis, pedicle screw fixation is required after traditional laminectomy, but there are many complications. In recent years, tumour resection and laminectomy have become increasingly favoured by clinicians. However, the comparison of the clinical effects of lamina complex replantation and pedicle screw fixation after laminectomy in the treatment of intraspinal tumours is still unknown. This paper systematically compared the two methods from many aspects and discussed their advantages and disadvantages to obtain better clinical guidance. MATERIALS AND METHODS: In this study, a retrospective analysis was conducted to select 58 patients who underwent posterior approach tumour resection in the spinal surgery department of our hospital from January 2017 to January 2020. Among them, 32 patients underwent tumour resection and laminoplasty, and 26 patients underwent tumour resection and screw internal fixation. The age, sex, body mass index (BMI), smoking status, duration of symptoms, operation time, length of hospital stay, postoperative complications, amount of bleeding and other data were summarized, calculated and compared. RESULTS: 1. The age, sex, BMI, smoking status and symptom duration of the two groups were compared. The abovementioned results were not statistically significant. 2. The operation time, hospital stay, postoperative complications, intraoperative bleeding and adjacent segment degeneration (ASD) were counted and compared between the two groups. There was no significant difference in hospital stay or intraoperative bleeding between the two groups; in addition, the operation time, postoperative complications and incidence of ASD were statistically significant. 3. The visual analog scale (VAS) score, Oswestry Disability Index (ODI) score of thoracic and lumbar spines and Neck Disability Index (NDI) score of cervical spine patients in the two groups were counted, and the preoperative and postoperative data, as well as their changes, were counted and compared between groups and within groups. There was no statistical significance between the two groups; moreover, the postoperative scores were all significantly lower than preoperative in the group. 4. According to the spinal cord function ASIA grade, the preoperative, final follow-up and change values of the two groups were counted, and intragroup and intergroup comparisons were made. There was no significant difference between the two groups; in addition, the scores of the final follow-up were significantly higher than preoperative in the group. 5. The spinal mobility was measured and recorded before the operation and at the final follow-up. There was no significant difference between preoperative and postoperative cervical mobility, and there was no statistical significance observed; furthermore, the range of flexion, extension, rotation and lateral bending of the thoracic and lumbar spines in the screw fixation group was significantly lower than that in the lamina replantation group. CONCLUSIONS: Lamina replantation can be used as splendid methods for the treatment of Intraspinal tumour. Lamina replantation can reduce the operation time, as well as reduce the occurrence of postoperative cerebrospinal fluid leakage, iatrogenic spinal stenosis, posterior soft tissue adhesion and ASD. These complications are reduced in comparison to the other mode of management and better preserve the mobility of the spine.

Acupuncture combined with moxibustion mitigates spinal cord injury-induced motor dysfunction in mice by NLRP3-IL-18 signaling pathway inhibition.

BACKGROUND: Spinal cord injury (SCI), which reportedly induces severe motor dysfunction, imposes a significant social and financial burden on affected individuals, families, communities, and nations. Acupuncture combined with moxibustion (AM) therapy has been widely used for motor dysfunction treatment, but the underlying mechanisms remain unknown. In this work, we aimed to determine whether AM therapy could alleviate motor impairment post-SCI and, if so, the potential mechanism. METHODS: A SCI model was established in mice through impact methods. AM treatment was performed in SCI model mice at Dazhui (GV14) and Jiaji points (T7-T12), Mingmen (GV4), Zusanli (ST36), and Ciliao (BL32) on both sides for 30 min once per day for 28 days. The Basso-Beattie-Bresnahan score was used to assess motor function in mice. A series of experiments including astrocytes activation detected by immunofluorescence, the roles of NOD-like receptor pyrin domain-containing-3 (NLRP3)-IL-18 signaling pathway with the application of astrocyte-specific NLRP3 knockout mice, and western blot were performed to explore the specific mechanism of AM treatment in SCI. RESULTS: Our data indicated that mice with SCI exposure exhibited motor dysfunction, a significant decrease of neuronal cells, a remarkable activation of astrocytes and microglia, an increase of IL-6, TNF-α, IL-18 expression, and an elevation of IL-18 colocalized with astrocytes, while astrocytes-specific NLRP3 knockout heavily reversed these changes. Besides, AM treatment simulated the neuroprotective effects of astrocyte-specific NLRP3 knockout, whereas an activator of NLRP3 nigericin partially reversed the AM neuroprotective effects. CONCLUSION: AM treatment mitigates SCI-induced motor dysfunction in mice; this protective mechanism may be related to the NLRP3-IL18 signaling pathway inhibition in astrocytes.

Hypomethylation of Tumor necrosis factor-like cytokine 1A(TL1A) and its decoy receptor 3 expressive level increase has diagnostic value in HBV-associated cirrhosis.

For patients with cirrhosis, early diagnosis is the key to delaying the development of liver fibrosis and improving prognosis. This study aimed to investigate the clinical significance of TL1A, which is a susceptibility gene for hepatic fibrosis, and DR3 in the development of cirrhosis and fibrosis. We analyzed the expression of TL1A, DR3, and other inflammatory cytokines associated with liver fibrosis in serum and PBMCs in 200 patients.TL1A methylation level was lower in patients with HBV-associated LC than in the other groups. In addition, the mRNA level and serum of TL1A and DR3 expression levels were found to increase in the LC. Hypomethylation of the TL1A promoter is present in HBV-associated LC, and TL1A and DR3 are highly expressed in HBV-associated cirrhosis. These results indicate that TL1A and DR3 may play an important role in the pathogenesis of LC and TL1A methylation levels may serve as a noninvasive biomarker for early diagnosis and progression of LC.

Effects of N fertilizer reduction combined with straw biochar application on the yield, Si, and N nutrition of double-cropping rice.

Nitrogen (N) and silicon (Si) are important nutritional elements for rice. However, excessive N fertili-zer application and the ignorance of Si fertilizer are common in practice. Straw biochar is rich in Si, which can be used as a potential Si fertilizer. In this study, we conducted a consecutive 3-year field experiment to explore the effects of N fertilizer reduction combined with straw biochar application on rice yield, Si and N nutrition. There were five treatments: conventional N application (180 kg·hm-2, N100), 20% N reduction (N80), 20% N reduction with 15 t·hm-2 biochar (N80+BC), 40% N reduction (N60), and 40% N reduction with 15 t·hm-2 biochar (N60+BC). The results showed that compared with N100, 20% N reduction did not affect the accumulation of Si and N in rice; 40% N reduction reduced foliar N absorption, but significantly increased foliar Si concentration by 14.0%-18.8%; while combined application of biochar significantly increased foliar Si accumulation, with an increase of Si concentration by 38.0%-63.3% and Si absorption by 32.3%-49.9%, but further reduced foliar N concentration. There was a significant negative correlation between Si and N concentration in mature rice leaves, but no correlation between Si and N absorption. Compared with N100, N reduction or combined application of biochar did not affect soil ammonium N and nitrate N, but increased soil pH. Nitrogen reduction combined application of biochar significantly increased soil organic matter by 28.8%-41.9% and available Si content by 21.1%-26.9%, with a significant positive correlation between them. Compared with N100, 40% N reduction reduced rice yield and grain setting rate, while 20% N reduction and combined application of biochar did not influence rice yield and yield components. In summary, appropriate N reduction and combined with straw biochar can not only reduce N fertilizer input, but also improve soil fertility and Si supply, which is a promising fertilization method in double-cropping rice fields.

Trophectoderm biopsy is associated with adverse obstetric outcomes rather than neonatal outcomes.

BACKGROUND: With the wide application of preimplantation genetic testing (PGT) with trophectoderm (TE) biopsy, the safety of PGT has always been a concern. Since TE subsequently forms the placenta, it is speculated that the removal of these cells was associated with adverse obstetrical or neonatal outcomes after single frozen-thawed blastocyst transfer (FBT). Previous studies report contradictory findings with respect to TE biopsy and obstetric and neonatal outcomes. METHODS: We conducted a retrospective cohort study including 720 patients with singleton pregnancies from single FBT cycles who delivered at the same university-affiliated hospital between January 2019 and March 2022. The cohorts were divided into two groups: the PGT group (blastocysts with TE biopsy, n = 223) and the control group (blastocysts without biopsy, n = 497). The PGT group was matched with the control group by propensity score matching (PSM) analysis at a ratio of 1:2. The enrolled sample sizes in the two groups were 215 and 385, respectively. RESULTS: Patient demographic characteristics were comparable between the groups after PSM except for the proportion of recurrent pregnancy loss, which was significantly higher in the PGT cohort (31.2 vs. 4.2%, P < 0.001). Patients in the PGT group had significantly higher rates of gestational hypertension (6.0 vs. 2.6%, adjusted odds ratio (aOR) 2.91, 95% confidence interval (CI) 1.18-7.18, P = 0.020) and abnormal umbilical cord (13.0 vs. 7.8%, aOR 1.94, 95% CI 1.08-3.48, P = 0.026). However, the occurrence of premature rupture of membranes (PROM) (12.1 vs. 19.7%, aOR 0.59, 95% CI 0.35-0.99, P = 0.047) was significantly lower in biopsied blastocysts than in unbiopsied embryos. There were no significant differences in regard to other obstetric and neonatal outcomes between the two groups. CONCLUSIONS: Trophectoderm biopsy is a safe approach, as the neonatal outcomes from biopsied and unbiopsied embryos were comparable. Furthermore, PGT is associated with higher risks of gestational hypertension and abnormal umbilical cord but may have a protective effect on PROM.

Transepithelial transport and cytoprotection of novel antioxidant peptides isolated from simulated gastrointestinal digestion of Xuanwei ham.

As a traditional fermented meat product, dry-cured Xuanwei ham could be a rich source of bioactive peptides. This study intended to investigate the transepithelial transport and cytoprotection of antioxidant peptides isolated from simulated gastrointestinal digestion of Xuanwei ham. Through ultrafiltration and gel filtration chromatography after simulated digestion, five new antioxidative cell-penetrating peptides (CPPs) with 16-27 amino acid residues were identified, and protective effects of the pretreatment with GHYTEGAELVDSVLDVVRK (GK-19) and TDEFQLHTNVNDGTEFGGSIYQK (TK-23) on H2O2-induced damaged HepG2 cells were investigated. The results showed that the peptide TK-23 at 0.5 mg mL-1 showed a good antioxidant activity through upregulating the activity of antioxidant enzymes (CAT, SOD and GR) and decreasing the MDA level in H2O2-induced damaged HepG2 cells with a better protective effect compared to GSH. Our observations of novel antioxidant CPPs with 16-27 amino acid residues could enrich the antioxidative CPP database, and these findings could provide data support for further study of CPPs.

Repressing IRS1/2 by NT157 inhibits the malignant behaviors of ovarian cancer through inactivating PI3K/AKT/mTOR pathway and inducing autophagy.

Insulin receptor substrate 1 and 2 (IRS1/2) have been found involved in many cancers development and their inhibitors exert significant tumor-suppressive effects. Here, we tried to explore the function of NT157, an IGF1R-IRS1/2 inhibitor, in ovarian cancer. We treated ovarian cancer cells with varying doses of NT157. The MTT assay was employed to evaluate cell proliferation and colony formation assay was used for detecting colony-forming ability. TUNEL assay was adopted to test cell apoptosis. Cell invasion was checked by the Transwell assay. The expression of apoptosis-related proteins, autophagy markers, IRS1/2, and PI3K/AKT/mTOR pathway was compared by Western blot, immunofluorescence, or qRT-PCR. As indicated by the data, NT157 abated the viability, proliferation, and induced autophagy of ovarian cancer cells. Overexpressing IRS1/2 attenuated the tumor-suppressive effect of NT157 and heightened the PI3K/AKT/mTOR pathway activation. Inhibition of the PI3K/AKT/mTOR pathway enhanced the tumor-suppressive effect of NT157 and facilitated NT157-mediated autophagy. However, the autophagy inhibitor 3-MA partly reversed NT-157-mediated antitumor effects. In conclusion, this study disclosed that NT157 suppressed the malignant phenotypes of ovarian cancer cells by inducing autophagy and hampering the expression of IRS1/2 and PI3K/AKT/mTOR pathway.