Parkin-mediated mitophagy is a potential treatment for oxaliplatin-induced peripheral neuropathy.

Oxaliplatin-induced peripheral nerve pain (OIPNP) is a common chemotherapy-related complication, but the mechanism is complex. Mitochondria are vital for cellular homeostasis and regulating oxidative stress. Parkin-mediated mitophagy is a cellular process that removes damaged mitochondria, exhibiting a protective effect in various diseases; however, its role in OIPNP remains unclear. In this study, we found that Parkin-mediated mitophagy was decreased, and reactive oxygen species (ROS) was upregulated in OIPNP rat dorsal root ganglion (DRG) in vivo and in PC12 cells stimulated with oxaliplatin (OXA) in vitro. Overexpression of Parkin indicated that OXA might cause mitochondrial and cell damage by inhibiting mitophagy. We also showed that salidroside (SAL) upregulated Parkin-mediated mitophagy to eliminate damaged mitochondria and promote PC12 cell survival. Knockdown of Parkin indicated that mitophagy is crucial for apoptosis and mitochondrial homeostasis in PC12 cells. In vivo study also demonstrated that SAL enhances Parkin-mediated mitophagy in the DRG and alleviates peripheral nerve injury and pain. These results suggest that Parkin-mediated mitophagy is involved in the pathogenesis of OIPNP and may be a potential therapeutic target for OIPNP.NEW & NOTEWORTHY This article discusses the effects and mechanisms of Parkin-mediated mitophagy in oxaliplatin-induced peripheral nerve pain (OIPNP) from both in vivo and in vitro. We believe that our study makes a significant contribution to the literature because OIPNP has always been the focus of clinical medicine, and mitochondrial quality regulation mechanisms especially Parkin-mediated mitophagy, have been deeply studied in recent years. We use a variety of molecular biological techniques and animal experiments to support our argument.

HSP90 Inhibition Attenuated Isoflurane-Induced Neurotoxicity in Mice and Human Neuroglioma Cells.

Isoflurane, a widely used inhalation anesthetic in clinical practice, is associated with an increased risk of neuronal injury. Heat shock protein 90 (HSP90) plays a crucial role in maintaining neuronal homeostasis under stress conditions; however, its role during isoflurane exposure remains poorly understood. In this study, we aimed to investigate the protective effects of HSP90 inhibition and explore the regulatory mechanisms underlying these effects during isoflurane exposure. We found that the HSP90 inhibitor 17-N-allylamino-17-demethoxygeldanamycin (17 AAG) has great protective effects in mitigating isoflurane-induced ferroptosis of mouse hippocampus and cultured neuronal cells. We focused on the activity of the crucial protein GPX4 in ferroptosis and found that 17 AAG exerted protective effects, preserving the physiological GPX4 activity under isoflurane exposure; further, 17 AAG restored the protein level of GPX4. Further, we observed that the chaperone-mediated autophagy (CMA) pathway was activated; 17 AAG also mediated GPX4 degradation under isoflurane exposure. Additionally, it interfered with the formation of complexes between HSP90 and Lamp-2a, inhibiting CMA activity, followed by the blockade of GPX4 degradation, further affecting the isoflurane-induced ferroptosis. Based on these findings, we proposed HSP90 inhibition as a protective mechanism against isoflurane-induced ferroptosis in neurons.

Progress in Research on the Effect of Melatonin on Postoperative Cognitive Dysfunction in Older Patients.

Postoperative cognitive dysfunction (POCD) is a common complication of the central nervous system in elderly patients after operation. It will prolong the length of stay, reduce the independence and quality of daily life, and increase the risk of death. However, at present, there is a lack of safe and effective ideal drugs for the prevention and treatment of POCD. Melatonin is one of the hormones secreted by the pineal gland of the brain, which has the functions of regulating circadian rhythm, anti-inflammation, anti-oxidation, anti-apoptosis, and so on. Some recent studies have shown that MT can prevent and treat POCD by adjusting circadian rhythm, restoring cholinergic system function, neuroprotection, and so on. This article will introduce POCD, melatonin and the mechanism of melatonin on POCD, respectively, to provide a basis for clinical prevention and treatment of POCD in the elderly.

A new anesthesia scheme for parathyroidectomy under neuromonitoring: a retrospective cohort study.

BACKGROUND: Parathyroidectomy under nerve monitoring has been carried out for nearly ten years in the China-Japan Union Hospital of Jilin University. We retrospectively evaluated patients' prognosis with secondary hyperparathyroidism (SH) under neuro- and non-neuro-monitored parathyroidectomy anesthesia. The purpose of this study is to summarize and introduce a new anesthesia scheme for parathyroidectomy under nerve monitoring. METHODS: From January 2000 to December 2019, 200 patients with SH in the China-Japan Union Hospital of Jilin University were retrospectively analyzed. Among them, 100 patients underwent parathyroidectomy under neurological monitoring (Group A), and 100 patients underwent parathyroidectomy without neurological monitoring (Group B). The dosage of muscle relaxant, parathyroid hormone (PTH), serum calcium, phosphorus, urea, creatinine, and alkaline phosphatase (ALP) was recorded before surgery (T0), after surgery (T1), at discharge (T2), during skin incision (Ta), at four parathyroidectomies (Tb), and 10 min after total removal. The levels of PTH were measured at four-time points (Tc) and 30 minutes (Td) after complete resection. RESULTS: After screening and propensity score match (PSM), the data of 92 patients were analyzed. Group A's muscle relaxant dose was significantly less than Group B; the length of hospital stay in Group A was significantly lower than in Group B (P<0.05). The serum calcium levels, phosphorus, urea, and creatinine at T2 in Group A were lower than those in Group B (P<0.05). CONCLUSIONS: Parathyroid nerve monitoring technology combined with preoperative complete anesthesia scheme, anesthesia induction with one time ED95 (95% effective drug dose) cis-atracurium, end breath gas, and sevoflurane maintenance anesthesia under BIS monitoring can improve the prognosis of patients, shorten the length of hospital stay, and is effective and safe.

Bispectral index monitoring of the clinical effects of propofol closed-loop target-controlled infusion: Systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: To investigate whether closed-loop systems under bispectral index anesthesia depth monitoring can reduce the intraoperative propofol dosage. METHODS: All randomized controlled trials (RCTs) on reducing propofol dosage under closed-loop systems were collected, and the literature was screened out, the abstracts and full texts were carefully read, and the references were tracked, data extraction and quality evaluation were conducted on the included research, and the RevMan5.3 software was used for meta-analysis. The main results were propofol and the incidence of adverse reactions such as hypertensive hypotension and postoperative cognitive dysfunction. A total of 879 cases were included in 8 articles, including 450 occurrences in the closed-loop system group and 429 cases in the open-loop system group. RESULTS: Compared with manual control, closed-loop systems under bispectral index anesthesia depth monitoring reduced the dose of propofol (MD: -0.62, 95% CI: -1.08--0.16, P = .008), with heterogeneity (I2 = 80%). Closed-loop systems significantly reduced the incidence of abnormal blood pressure (MD: -0.02, 95%CI: -0.05-0.01, P = .15, I2 = 74%) and postoperative cognitive dysfunction (MD: -0.08, 95% CI: -0.14 -0.01, P = .02, I2 = 94%). CONCLUSION: Bispectral index monitoring of propofol closed-loop target-controlled infusion system can reduce the amount of propofol, reduce the incidence of adverse reactions such as hypertensive or hypotension and postoperative cognitive dysfunction.

A case report of unusual cavity presentation of pulmonary extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue.

RATIONALE: The common CT scan findings of pulmonary MZBL of MALT type include airspace consolidation, nodules and ground-glass opacity. But, to our knowledge, the present case is the first report of a cavity presentation of pulmonary MZBL of MALT type. PATIENT CONCERNS: The patient gives his consent and authorizes the photographs featuring his likeness to be published. DIAGNOSES: This patient was diagnosed as pulmonary MZBL of MALT type by pathology, immunohistochemistry, and gene rearrangement. INTERVENTIONS: The patient was treated with CHOP (cyclophosphamide, adriamycin, vincristine and prednisone) chemotherapy for twice and antibiotics. OUTCOMES: He is being followed up for one year, with slight progress in pulmonary MZBL of MALT. LESSONS: This case highlights the need to be suspicious of MZBL of MALT type, when a radiographic image shows cavity lesion. We should consider whether the diagnosis is correct, when the patient's treatment is not effective.

Domain III of Bacillus thuringiensis Cry1Ie Toxin Plays an Important Role in Binding to Peritrophic Membrane of Asian Corn Borer.

The insecticidal IE648 toxin is a truncated Cry1Ie protein with increased toxicity against Asian corn borer (ACB). Cry toxins are pore-forming toxins that disrupt insect midgut cells to kill the larvae. However, the peritrophic membrane (PM) is an important barrier that Cry toxins must cross before binding to midgut cells. Previously, it was shown that Cry toxins are able to bind and accumulate in the PM of several lepidopteran insects. Binding of IE648 toxin to PM of ACB was previously reported and the goal of the current work was the identification of the binding region between Cry1Ie and the PM of ACB. Homologous competition binding assays showed that this interaction was specific. Heterologous competition binding assays performed with different fragments corresponding to domain I, domain II and domain III allowed us to identify that domain III participates in the interaction of IE648 with the PM. Specifically, peptide D3-L8 (corresponding to Cry1Ie toxin residues 607 to 616), located in an exposed loop region of domain III is probably involved in this interaction. Ligand blot assays show that IE648 interact with chitin and PM proteins with sizes of 30, 32 and 80 kDa. The fact that domain III interacts with proteins of similar molecular masses supports that this region of the toxin might be involved in PM interaction. These data provide for the first time the identification of domain III as a putative binding region between PM and 3D-Cry toxin.

Purification of an active fragment of Cry1Ie toxin from Bacillus thuringiensis.

The cry1I genes from Bacillus thuringiensis are a class of special genes with unique characteristics; they are silent in B. thuringiensis strains but can be over-expressed in Escherichia coli, resulting in a Cry1I-type protein with a molecular mass of approximately 81kDa. Cry1I-type protein is toxic to Lepidoptera larvae. A truncated Cry1Ie protein, IE648, which corresponds to the first 648 amino acids from the N-terminus of Cry1Ie, was purified from E. coli using Ni-NTA affinity isolation, Q-Sepharose Fast Flow chromatography, and Superdex-200 size-exclusion chromatography. It was determined using laboratory bioassays that the purified IE648 protein has good insecticidal activity. Heterologous competitive binding assays show that IE648 does not compete with Cry1Ac for binding to the brush border membrane vesicles of the Asian corn borer and does not compete with Cry1Ac at concentrations below a 500-fold excess of unlabeled Cry1Ac for binding to the peritrophic matrix of the insect. This result implies that IE648 may be a good candidate as part of a multiple-toxin strategy for the potential control of resistance in insect pests. The method of purification reported here is valuable for further research on the structure and function of IE648 and in evaluating the biosafety of this protein within transgenic plants.