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1.
Biomed Mater Eng ; 2024 May 16.
Article En | MEDLINE | ID: mdl-38758990

BACKGORUND: The development of vibration-induced finger disorders is likely associated with combined static and dynamic responses of the fingers to vibration exposure. To study the mechanism of the disorders, a new rat-tail model has been established to mimic the finger vibration and pressure exposures. However, the mechanical behavior of the tail during compression needs to be better understood to improve the model and its applications. OBJECTIVE: To investigate the static and time-dependent force responses of the rat tail during compression. METHODS: Compression tests were conducted on Sprague-Dawley cadaver rat tails using a micromechanical system at three deformation velocities and three deformation magnitudes. Contact-width and the time-histories of force and deformation were measured. Additionally, force-relaxation tests were conducted and a Prony series was used to model the force-relaxation behavior of the tail. RESULTS: The rat tails' force-deformation and stiffness-deformation relationships were strongly nonlinear and time-dependent. Force/stiffness increased with an increase in deformation and deformation velocity. The time-dependent force-relaxation characteristics of the tails can be well described using a Prony series. CONCULSIONS: We successfully quantified the static and time-dependent force responses of rat tails under compression. The identified mechanical behavior of the tail can help improve the rat-tail model and its applications.

2.
Biomed Mater Eng ; 2024 Apr 23.
Article En | MEDLINE | ID: mdl-38669519

BACKGROUND: Wearing protective helmets is an important prevention strategy to reduce work-related traumatic brain injuries. The existing standardized testing systems are used for quality control and do not provide a quantitative measure of the helmet performance. OBJECTIVE: To analyze the failure characterizations of Type I industrial helmets and develop a generalized approach to quantify the shock absorption performance of Type I industrial helmets based on the existing standardized setups. METHODS: A representative basic Type I construction helmet model was selected for the study. Top impact tests were performed on the helmets at different drop heights using two different impactor masses (3.6 and 5.0 kg). RESULTS: When the helmets were impacted with potential impact energies smaller than the critical potential impact energy values, there was a consistent relationship between the peak impact force and the potential impact energy. When the helmets were impacted under potential impact energies greater than the critical potential impact energy values, the peak impact forces increased steeply with increasing potential impact energy. CONCLUSION: A concept of safety margin for construction helmets based on potential impact energy was introduced to quantify the helmets' shock absorption performance. The proposed method will help helmet manufacturers improve their product quality.

4.
JSES Int ; 8(2): 282-286, 2024 Mar.
Article En | MEDLINE | ID: mdl-38464451

Background: To compare the complications and efficacy of pain relief of the interscalene anesthetic block using either a single-injection (SI) vs. a continuous, indwelling catheter (CIC) for arthroscopic rotator cuff repair surgery. Methods: Patients undergoing primary, arthroscopic rotator cuff repair without concomitant open procedure or biceps tenodesis were prospectively enrolled by 4 fellowship-trained sports medicine and shoulder surgeons. Patients received either a SI or CIC preoperatively based on surgeon preference. Patients were contacted by phone to complete a standard questionnaire on postoperative days (PODs) 1, 3, 7, 14, and 28. Patients were asked to rate the efficacy of their subjective pain relief (scale of 0-10), document issues with the catheter, describe analgesic usage, and report pharmacological and medical complications. The primary outcome was measured as complication rate. Postoperative narcotic use, patient satisfaction, and visual analog scale pain scores were measured as secondary outcomes. Results: Seventy patients were enrolled, 33 CIC patients (13 male, 20 female, mean age 61 ± 8 years) and 37 SI patients (20 male, 17 female, mean age 59 ± 10 years). There were significantly more injection/insertion site complications in the CIC group (48%) vs. the SI group (11%, P = .001). The incidence of motor weakness was higher in the CIC group on POD 1 (P = .034), but not at any subsequent time points. On POD 1, CIC patients had a clinically significantly lower pain score compared to SI (3.2 vs. 5.4; P = .020). Similar scores were observed at subsequent time points until POD 28, when CIC again had a lower pain score (0.8 vs. 2.7; P = .005). However, this did not reach clinical significance. All patients in both groups rated a satisfaction of 9 or 10 (scale 0-10) with the anesthesia provided by their nerve block. Conclusion: CIC interscalene nerve blocks had an increased risk for injection site complications and minor complications in the immediate postoperative period when using the CIC for arthroscopic rotator cuff repair without any concomitant open procedures. CIC blocks demonstrated clinically significant superior pain relief on POD 1 but were equal to SI blocks at every time point thereafter. Superior pain relief of CIC at POD 28 was not clinically significant. CIC catheters do not appear to markedly decrease the use of postoperative narcotics. Despite this trend in complication rates and pain scores, all patients in both groups were satisfied with their nerve block.

5.
NPJ Syst Biol Appl ; 9(1): 46, 2023 09 22.
Article En | MEDLINE | ID: mdl-37736766

Mechanistic models are commonly employed to describe signaling and gene regulatory kinetics in single cells and cell populations. Recent advances in single-cell technologies have produced multidimensional datasets where snapshots of copy numbers (or abundances) of a large number of proteins and mRNA are measured across time in single cells. The availability of such datasets presents an attractive scenario where mechanistic models are validated against experiments, and estimated model parameters enable quantitative predictions of signaling or gene regulatory kinetics. To empower the systems biology community to easily estimate parameters accurately from multidimensional single-cell data, we have merged a widely used rule-based modeling software package BioNetGen, which provides a user-friendly way to code for mechanistic models describing biochemical reactions, and the recently introduced CyGMM, that uses cell-to-cell differences to improve parameter estimation for such networks, into a single software package: BioNetGMMFit. BioNetGMMFit provides parameter estimates of the model, supplied by the user in the BioNetGen markup language (BNGL), which yield the best fit for the observed single-cell, time-stamped data of cellular components. Furthermore, for more precise estimates, our software generates confidence intervals around each model parameter. BioNetGMMFit is capable of fitting datasets of increasing cell population sizes for any mechanistic model specified in the BioNetGen markup language. By streamlining the process of developing mechanistic models for large single-cell datasets, BioNetGMMFit provides an easily-accessible modeling framework designed for scale and the broader biochemical signaling community.


Signal Transduction , Software , Kinetics , RNA, Messenger , Signal Transduction/genetics , Systems Biology
7.
Br J Cancer ; 129(5): 797-810, 2023 09.
Article En | MEDLINE | ID: mdl-37474720

BACKGROUND: The aim of this study was to investigate the antitumour activity, safety, and tolerability of pamiparib plus tislelizumab in patients with previously treated advanced solid tumours. METHODS: In this study, patients were enrolled into eight arms by tumour type. All received pamiparib 40 mg orally twice daily plus tislelizumab 200 mg intravenously every 3 weeks. The primary endpoint was objective response rate (ORR), assessed by the investigator per Response Evaluation Criteria in Solid Tumours v1.1. Secondary endpoints included duration of response (DoR), safety, and tolerability. RESULTS: Overall, 180 patients were enrolled. In the overall population, the ORR was 20.0% (range: 0-47.4 across study arms), with median DoR of 17.1 months (95% confidence interval [CI]: 6.2, not estimable [NE]). The highest ORR was observed in the triple-negative breast cancer (TNBC) arm (patients with BRCA1/2 mutations and/or homologous recombination deficiency) (ORR: 47.4%; median DoR: 17.1 months [95% CI: 3.0, NE]). Treatment-emergent adverse events (TEAEs) of ≥Grade 3 occurred in 61.7% of patients. Serious TEAEs occurred in 50.0% of patients. CONCLUSIONS: Pamiparib plus tislelizumab showed a variable level of antitumour activity in patients with advanced solid tumours, with the highest ORR in TNBC and was associated with a manageable safety profile. CLINICAL TRIAL REGISTRATION: ClinicalTrial.gov: NCT02660034.


BRCA1 Protein , Triple Negative Breast Neoplasms , Humans , BRCA2 Protein , Antineoplastic Combined Chemotherapy Protocols/adverse effects
8.
Eur J Haematol ; 111(4): 544-552, 2023 Oct.
Article En | MEDLINE | ID: mdl-37439123

INTRODUCTION: Simoctocog alfa (Nuwiq®) is a 4th generation recombinant FVIII with proven efficacy for the prevention and treatment of bleeding episodes (BEs) in previously treated patients with severe haemophilia A. The NuProtect study assessed the immunogenicity, efficacy and safety of simoctocog alfa in 108 previously untreated patients (PUPs). The incidence of high-titre inhibitors was 16.2% and no patients with non-null F8 mutations developed inhibitors. AIM: To report the efficacy and safety results from the NuProtect study. METHODS: PUPs received simoctocog alfa for prophylaxis, treatment of BEs, or as surgical prophylaxis. The efficacy of prophylaxis (during inhibitor-free periods) was assessed using annualised bleeding rates (ABRs). The efficacy in treating BEs and in surgical prophylaxis was assessed using a 4-point scale. Adverse events were recorded throughout the study. RESULTS: Of 108 PUPs treated with simoctocog alfa, 103 received at least one prophylactic dose and 50 received continuous prophylaxis for at least 24 weeks. In patients on continuous prophylaxis, the median ABR was 0 (mean 0.5) for spontaneous BEs and 2.5 (mean 3.6) for all BEs. In 85 patients who had BEs, efficacy of BE treatment was excellent or good for 92.9% (747/804) of rated BEs; 92.3% of BEs were treated with 1 or 2 infusions. The efficacy of surgical prophylaxis was excellent or good for 94.7% (18/19) of rated procedures. There were no safety concerns and no thromboembolic events. CONCLUSION: Simoctocog alfa was efficacious and well tolerated as prophylaxis, surgical prophylaxis and for the treatment of BEs in PUPs with severe haemophilia A.


Hemophilia A , Humans , Hemophilia A/drug therapy , Hemophilia A/surgery , Factor VIII/adverse effects , Factor VIII/genetics , Hemorrhage/prevention & control , Hemorrhage/chemically induced , Treatment Outcome
9.
Proc Inst Mech Eng H ; 237(7): 890-904, 2023 Jul.
Article En | MEDLINE | ID: mdl-37345449

It has been hypothesized that the biodynamic responses of the human finger tissues to vibration are among the major stimuli that cause vibration health effects. Furthermore, the finger contact pressure can alter these effects. It is difficult to test these hypotheses using human subjects or existing animal models. The objective of this study was to develop a new rat-tail vibration model to investigate the combined effects of vibration and contact pressure and to identify their relationships with the biodynamic responses. Physically, the new exposure system was developed by adding a loading device to an existing rat-tail model. An analytical model of the rat-tail exposure system was proposed and used to formulate the methods for quantifying the biodynamic responses. A series of tests with six tails dissected from rat cadavers were conducted to test and evaluate the new model. The experimental and modeling results demonstrate that the new model behaves as predicted. Unlike the previous model, the vibration strain and stress of the rat tail does not depend primarily on the vibration response of the tail itself but on that of the loading device. This makes it possible to quantify and control the biodynamic responses conveniently and reliably by measuring the loading device response. This study also identified the basic characteristics of the tail biodynamic responses in the exposure system, which can be used to help design the experiments for studying vibration biological effects.


Tail , Vibration , Humans , Rats , Animals , Fingers/physiology , Upper Extremity , Cadaver
10.
Haemophilia ; 29(4): 1005-1012, 2023 Jul.
Article En | MEDLINE | ID: mdl-37335546

BACKGROUND: The NuProtect study reported data on the immunogenicity, efficacy and tolerability of simoctocog alfa (Nuwiq® ) in 108 previously untreated patients with severe haemophilia A planned to be treated for ≥100 exposure days or up to 5 years. The NuProtect-Extension study collected long-term prophylaxis data in children with severe haemophilia A. METHODS: Patients who completed the NuProtect study according to the protocol were eligible for the NuProtect-Extension study, a prospective, multinational, non-controlled, Phase 3b study. RESULTS: Of 48 patients who entered the extension study, 47 (median age 2.8 years) received prophylaxis with simoctocog alfa for a median of 24 months, with 82%-88% on a twice-weekly or less regimen. No patient developed FVIII inhibitors during the extension study. The median (IQR) annualized bleeding rate (ABR) during prophylaxis was 0 (0-0.5) for spontaneous bleeding episodes (BEs) and 1.00 (0-1.95) for all BEs. ABRs estimated using a negative binomial model were .28 (95% CI: .15, .53) for spontaneous and 1.62 (95% CI: 1.09, 2.42) for all BEs. During the median follow-up of 24 months, 34 (72%) patients had zero spontaneous BEs and 46 (98%) had zero spontaneous joint BEs. Efficacy in treating BEs was excellent or good for 78.2% of rated BEs, and efficacy of surgical prophylaxis was excellent for two rated surgeries. No treatment-related adverse events were reported. CONCLUSION: No FVIII inhibitors developed during long-term prophylaxis in the NuProtect-Extension study. Prophylaxis with simoctocog alfa was efficacious and well-tolerated, and is therefore an attractive long-term option for children with severe haemophilia A.


Hemophilia A , Child, Preschool , Humans , Factor VIII/adverse effects , Hemophilia A/complications , Hemophilia A/drug therapy , Hemorrhage/etiology , Hemorrhage/prevention & control , Prospective Studies , Treatment Outcome , Child
11.
J Mech Med Biol ; 23(3)2023 Jan 28.
Article En | MEDLINE | ID: mdl-37361026

The anterior and posterior iliac spine markers frequently used to define the pelvis, are commonly occluded during three-dimensional (3D) motion capture. The occlusion of these markers leads to the use of various tracking marker configurations on the pelvis, which affect kinematic results. The purpose of this investigation was to examine the agreement of CODA pelvis kinematic results when two different tracking marker configurations were used during roofing tasks. 3D motion data were collected on seven male subjects while mimicking two roofing tasks. Hip joint angles (HJAs) were computed using the CODA pelvis with two different tracking marker configurations, the trochanter tracking method (TTM), and virtual pelvis tracking method (VPTM). Agreement between tracking marker configurations was assessed using cross-correlations, bivariate correlations, mean absolute differences (MADs), and Bland-Altman (BA) plots. The correlations displayed no time lag and strong agreement (all r > 0.83) between the HJA from the VPTM and TTM, suggesting the timing occurrence of variables are comparable between the two tracking marker configurations. The MAD between the VPTM and TTM displayed magnitude differences, but most of the differences were within a clinically acceptable range. Caution should still be used when comparing kinematic results between various tracking marker configurations, as differences exist.

12.
Article En | MEDLINE | ID: mdl-37123506

Ream-and-run arthroplasty can improve pain and function in patients with glenohumeral arthritis while avoiding the complications and activity restrictions associated with a prosthetic glenoid component. However, stiffness is a known complication after ream-and-run arthroplasty and can lead to repeat procedures such as a manipulation under anesthesia (MUA) or open surgical revision. The objective of this study was to determine risk factors associated with repeat procedures indicated for postoperative stiffness after ream-and-run arthroplasty. Methods: We conducted a retrospective review of our shoulder arthroplasty database to identify patients who underwent ream-and-run arthroplasty and determined which patients underwent subsequent repeat procedures (MUA and/or open revision) indicated for postoperative stiffness. The minimum follow-up was 2 years. We collected baseline demographic information and preoperative and 2-year patient-reported outcome scores and analyzed preoperative radiographs. Univariate and multivariate analyses determined the factors significantly associated with repeat procedures to treat postoperative stiffness. Results: There were 340 patients who underwent ream-and-run arthroplasty. The mean Simple Shoulder Test (SST) scores for all patients improved from 5.0 ± 2.4 preoperatively to 10.2 ± 2.6 postoperatively (p < 0.001). Twenty-six patients (7.6%) underwent open revision for stiffness. An additional 35 patients (10.3%) underwent MUA. Univariate analysis found younger age (p = 0.001), female sex (p = 0.034), lower American Society of Anesthesiologists (ASA) class (p = 0.045), posterior decentering on preoperative radiographs (p = 0.010), and less passive forward elevation at the time of discharge after ream-and-run arthroplasty (p < 0.001) to be significant risk factors for repeat procedures. Multivariate analysis found younger age (p = 0.040), ASA class 1 compared with class 3 (p = 0.020), and less passive forward elevation at discharge (p < 0.001) to be independent risk factors for repeat procedures. Of the patients who underwent open revision for stiffness, 69.2% had multiple positive cultures for Cutibacterium. Conclusions: Younger age, ASA class 1 compared with class 3, and less passive forward elevation in the immediate postoperative period were independent risk factors for repeat procedures to treat postoperative stiffness after ream-and-run arthroplasty. Level of Evidence: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

13.
Trends Biotechnol ; 41(10): 1216-1219, 2023 10.
Article En | MEDLINE | ID: mdl-37236813

Chimeric antigen receptor T cells (CAR-T) have demonstrated their potential to revolutionize cancer treatment. However, manufacturing remains a challenge. Multiple manufacturing innovations [e.g., vector and gene engineering, process improvements, hardware innovation, digital innovation, and point-of-care (POC) manufacturing] have the potential to help realize the full potential of CAR-T therapies.


Receptors, Chimeric Antigen , Receptors, Chimeric Antigen/genetics , Immunotherapy, Adoptive , Cell- and Tissue-Based Therapy , Genetic Engineering
15.
Liver Cancer ; 12(1): 72-84, 2023 Feb.
Article En | MEDLINE | ID: mdl-36872927

Introduction: Tislelizumab (anti-programmed cell death protein 1 antibody) showed preliminary antitumor activity and tolerability in patients with advanced solid tumors, including hepatocellular carcinoma (HCC). This study aimed to assess the efficacy and safety of tislelizumab in patients with previously treated advanced HCC. Methods: The multiregional phase 2 study RATIONALE-208 examined single-agent tislelizumab (200 mg intravenously every 3 weeks) in patients with advanced HCC with Child-Pugh A, Barcelona Clinic Liver Cancer stage B or C, and who had received one or more prior lines of systemic therapy. The primary endpoint was objective response rate (ORR), radiologically confirmed per Response Evaluation Criteria in Solid Tumors version 1.1 by the Independent Review Committee. Safety was assessed in patients who received ≥1 dose of tislelizumab. Results: Between April 9, 2018, and February 27, 2019, 249 eligible patients were enrolled and treated. After a median study follow-up of 12.7 months, ORR was 13% (n = 32/249; 95% confidence interval [CI], 9-18), including five complete and 27 partial responses. The number of prior lines of therapy did not impact ORR (one prior line, 13% [95% CI, 8-20]; two or more prior lines, 13% [95% CI, 7-20]). Median duration of response was not reached. The disease control rate was 53%, and median overall survival was 13.2 months. Of the 249 total patients, grade ≥3 treatment-related adverse events were reported in 38 (15%) patients; the most common was liver transaminase elevations in 10 (4%) patients. Treatment-related adverse events led to treatment discontinuation in 13 (5%) patients or dose delay in 46 (19%) patients. No deaths were attributed to the treatment per investigator assessment. Conclusion: Tislelizumab demonstrated durable objective responses, regardless of the number of prior lines of therapy, and acceptable tolerability in patients with previously treated advanced HCC.

16.
Int Orthop ; 47(6): 1511-1515, 2023 06.
Article En | MEDLINE | ID: mdl-36977799

PURPOSE: The objective of this study was to characterize the temporal dynamics of Cutibacterium repopulation of the skin surface after application of chlorhexidine to the shoulder. METHODS: Ten shoulders in five male subjects were used. A skin swab was taken prior to (0 minutes) and then at three, 30, 60, 120, and 240 minutes after skin preparation with 2% chlorhexidine gluconate and 70% isopropyl alcohol. Semi-quantitative bacterial load was measured for each timepoint. RESULTS: From zero minutes (pre-treatment) to three minutes, chlorhexidine-isopropyl alcohol reduced the skin bacterial load in eight out of ten shoulders. Of these eight shoulders, four (50%) had growth by 30 minutes, seven (88%) had growth by 60 minutes, and all eight (100%) had growth by 240 minutes. Compared to the three minutes after chlorhexidine application, bacterial load had significantly increased by 60 minutes but were still significantly lower than the pre-prep bacterial load (0 minutes). CONCLUSION: Following standard surgical skin preparation with chlorhexidine-isopropyl alcohol, the surface of the shoulder is repopulated with Cutibacterium within one hour, presumably from reservoirs in sebaceous glands not penetrated by topical antiseptic agents. Since these dermal glands are transected by skin incision for shoulder arthroplasty, this study suggests that they may be sources of wound contamination during surgery in spite of skin preparation with chlorhexidine.


Anti-Infective Agents, Local , Chlorhexidine , Male , Humans , Shoulder , 2-Propanol , Surgical Wound Infection , Skin/microbiology , Preoperative Care
17.
Br J Cancer ; 128(8): 1418-1428, 2023 04.
Article En | MEDLINE | ID: mdl-36797356

BACKGROUND: Many patients do not respond or eventually relapse on treatment with programmed cell death protein-1 (PD-1)/programmed death-ligand 1 (PD-L1) checkpoint inhibitors due to secondary or acquired resistance; therefore, there is a need to investigate novel PD-1/PD-L1 inhibitors. METHODS: This open-label, non-randomised study investigated the safety and anti-tumour activity of BGB-A333, a PD-L1 inhibitor, alone and in combination with tislelizumab in patients with advanced solid tumours with progression during/after standard therapy. The primary objectives were to determine the recommended Phase 2 dose (RP2D), safety and tolerability for BGB-A333 alone and in combination with tislelizumab (Phase 1a/1b) and to determine the overall response rate (ORR) with BGB-A333 plus tislelizumab (Phase 2). RESULTS: Overall, 39 patients across Phase 1a (N = 15), 1b (N = 12) and 2 (N = 12) were enroled. In Phase 1a, an RP2D of 1350 mg was determined. In Phase 1a and 1b/2, serious treatment-emergent adverse events (TEAEs) were reported in five and eight patients, respectively. Two patients experienced TEAEs that led to death. In Phase 2, the ORR was 41.7% (n = 5/12; 95% confidence interval: 15.17%, 72.33%). CONCLUSIONS: TEAEs reported with BGB-A333 were consistent with other PD-L1 inhibitors. Encouraging preliminary anti-tumour activity was observed with BGB-A333 in combination with tislelizumab. CLINICAL TRIAL REGISTRATION: NCT03379259.


B7-H1 Antigen , Immune Checkpoint Inhibitors , Humans , Programmed Cell Death 1 Receptor , Neoplasm Recurrence, Local/drug therapy , Antibodies, Monoclonal/adverse effects
18.
Asian J Surg ; 46(1): 180-186, 2023 Jan.
Article En | MEDLINE | ID: mdl-35305874

BACKGROUND: Ulnar tunnel syndrome (UTS) is relatively uncommon compared to the carpal tunnel or cubital tunnel syndromes. Few reports dedicated to the functional outcomes after surgical intervention of the UTS exist. Herein we compare the outcomes of patients with UTS of different etiologies. METHODS: Patients diagnosed with UTS between 2016 and 2020 were recruited. Ulnar tunnel release was performed in all patients, along with other necessary osteosynthesis or reconstructive procedures in the traumatic group. Patients were followed-up every six months post-operatively. Outcomes measured include: objective evaluations, subjective questionnaires, records of clinical signs, and grading of the British Medical Research Council scale for intrinsic muscle strength. RESULTS: 21 patients were recruited, and favorable results were noted in all of them after surgery. Traumatic UTS patients had a worse initial presentation than the non-traumatic cases, but had a greater improvement after surgery and yielded outcomes comparable with those of the patients without trauma. Patients with aberrant muscles in their wrists had better outcomes in some objective measurements than those without aberrant muscles. CONCLUSIONS: Ulnar tunnel release improves the outcome of patients regardless of the etiology, especially in patients with trauma-induced UTS. Thus, a proper diagnosis of the UTS should be alerted in all patients encountering paresthesia in the ulnar digits, ulnar-sided pain, weakness of grip strength, or intrinsic weakness to ensure good outcomes.


Carpal Tunnel Syndrome , Cubital Tunnel Syndrome , Ulnar Nerve Compression Syndromes , Humans , Ulnar Nerve Compression Syndromes/etiology , Ulnar Nerve Compression Syndromes/surgery , Prospective Studies , Cubital Tunnel Syndrome/diagnosis , Cubital Tunnel Syndrome/etiology , Cubital Tunnel Syndrome/surgery , Carpal Tunnel Syndrome/surgery , Carpal Tunnel Syndrome/complications , Wrist
19.
Toxicol Rep ; 9: 219-229, 2022.
Article En | MEDLINE | ID: mdl-36518455

Previous studies from our laboratory showed that prenatal exposure to hexavalent chromium, Cr(VI), caused premature ovarian failure and decreased pregnancy rates and litter size. Exposure to the endocrine disrupting chemicals (EDCs) can cause X-chromosome aneuploidy of the oocytes, increasing chromosome missegregation and risk of infertility, autoimmune diseases, cancers, and various genetic disorders. Cr(VI) is an EDC that is widely used in numerous industries. Environmental exposure to Cr(VI) caused detrimental reproductive effects in women and health effects in infants from California. Women with occupational Cr(VI) exposure experienced infertility, pregnancy loss, spontaneous abortion, and stillbirth. However, the adverse effects of Cr(VI) on oocyte development and quality have not been reported. Mitochondrial membrane potential and function are the critical determinants of oocyte quality in natural pregnancies and successful assisted reproductive techniques. The cytoskeletal machinery of the oocytes orchestrates the meiotic division of the oocytes, whereas cortical granules (CGs) prevent polyspermy. Therefore, the objective of the current study was to examine whether the mechanism by which Cr(VI) compromises oocyte quality and morphology is by altering cytoskeleton dynamics and mitochondrial function of the metaphase II (MII) oocytes. Rats were treated with environmentally relevant doses of Cr(VI) (1 and 5 ppm potassium dichromate) in drinking water from postnatal day (PND) 22-28, followed by superovulation and retrieval of MII oocytes. The data indicate that Cr(VI) exposure disrupted F-actin structure and distribution pattern, compromised mitochondrial function, altered CGs distribution, increased dysmorphic and degenerated oocytes, delayed first polar body extrusion, and caused infertility.

20.
Inorg Chem ; 61(49): 19882-19889, 2022 Dec 12.
Article En | MEDLINE | ID: mdl-36441974

Ascidians use a class of cysteine-rich proteins generally referred to as vanabins to reduce vanadium ions, one of the many biological processes that involve the redox conversion between disulfide and dithiolate mediated by transition-metal ions. To further understand the nature of disulfide/dithiolate exchange facilitated by a vanadium center, we report herein a six-coordinate non-oxido VIV complex containing an unbound disulfide moiety, [VIV(PS3″)(PS1″S-S)] (1) (PS3″ = [P(C6H3-3-Me3Si-2-S)3]3-, where PS1″S-S is a disulfide form of PS3″). Complex 1 is obtained from a reaction of previously reported [VV(PS3″)(PS2″SH)] (2) (PS2″SH = [P(C6H3-3-Me3Si-2-SH)(C6H3-3-Me3Si-2-S)2] with TEMPO (TEMPO = 2,2,6,6-tetramethylpiperidin-1-yl)oxyl) via hydrogen atom transfer. Importantly, complex 1 can be reduced by two electrons to form an eight-coordinate VIV complex, [VIV(PS3″)2]2- (4). The reaction can be reversed through a two-electron oxidation process to regenerate complex 1. The redox pathways both proceed through a common intermediate, [V(PS3″)2]- (3), that has been previously reported as a resonance form of VV-dithiolate and a VIV-(thiolate)(thiyl-radical) species. This work demonstrates an unprecedented example of reversible disulfide/dithiolate interconversion mediated by a VIV center, as well as provides insights into understanding the function of VV reductases in vanabins.


Disulfides , Vanadium , Vanadium/metabolism , Oxidation-Reduction , Electrons , Hydrogen
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